Main Report

Download report 16 MB

Appendix 1: Understanding the science of vaccines | Āpitihanga 1: Te Mārama ki te Pūtaiao o ngā Werohanga

Many submitters expressed concerns about the safety of the COVID-19 vaccines, some of which are addressed in Part 2 of this report. Other concerns warrant further discussion, particularly as they require explanations about complex science. Appendix 1 provides a response to some of these concerns, in addition to, or in more detail than is discussed in Part 2 of this Report.

Submitters’ primary concerns about the safety of the COVID-19 vaccines can be categorised as follows.

mRNA vaccines (which use messenger RNA to instruct the body’s cells to produce a viral protein that evokes an immune response in the person receiving them) alter DNA or modify genes, causing cancer and other harmful conditions.
The manufacturing process for Comirnaty was changed which affected its safety.
The Comirnaty vaccine was still ‘experimental’ at the time of approval and had not been properly tested.
The Comirnaty vaccine produced harmful side effects which authorities have not acted on appropriately.
The long-term effects of the Comirnaty vaccine remain uncertain.

We have carefully considered these issues, drawing on advice and evidence from a range of experts and sources, including studies provided to us by submitters, research published in leading scientific journals and conclusions from international regulatory authorities and the COVID-19 Vaccine Independent Safety Monitoring Board. This review makes clear that the concerns raised are not grounded in reliable evidence or aligned with scientific consensus. While we acknowledge the sincerity of those who brought these concerns to us, ultimately our conclusions reflect the most robust and widely accepted scientific evidence available.

It is important to recognise that science speaks in probabilities rather than certainties; the following discussion does likewise. However, this language can be misunderstood. Saying something is improbable, implausible or theoretically possible is another way of saying we cannot exclude the possibility it could happen. However, we are not saying it will happen.

1.1 mRNA vaccines are not known to directly modify DNA | Kāore e kitea ana he pānga tōtika o ngā werohanga mRNA ki te whakarerekē i te DNA

A significant concern raised about the COVID-19 vaccines was that mRNA vaccines alter the DNA of vaccinated individuals. Submitters claimed that there is potential for mRNA vaccines to integrate into the genes of vaccinated individuals, modifying them and causing cancer and other conditions.

There are several ways they said that this occurs.

Residual DNA left in the vaccines during the manufacturing process integrates into the vaccinated person’s DNA.
The synthetic mRNA in the vaccine integrates into the vaccinated person’s DNA.
The mRNA vaccines contain a SV40 promoter (a small piece of DNA used to produce the mRNA in the Comirnaty vaccine), which is associated with cancer development.

The submitters cited studies and scientific opinion which they said supported their claim that the mRNA vaccines alter DNA. They said that because of this, the Comirnaty vaccine met international definitions of a ‘gene therapy’ and should have undergone more rigorous testing and longer safety follow-up, regulated by New Zealand’s Environmental Protection Authority.

1.1.1 Any residual DNA is below safety thresholds and does not integrate into the host DNA | Kei raro iho ngā toenga DNA i ngā paepae haumaru, ā, kāore e uru ki te DNA o te tangata

Some vaccines – including live-attenuated, inactivated and mRNA vaccines – can contain small amounts of DNA from the manufacturing process. For the Comirnaty vaccine, this occurs because the mRNA component of the vaccine is produced from a DNA template.¹²³⁷ After this step, the DNA is degraded (broken down) into very small fragments and removed,¹²³⁸ so any residual DNA is highly degraded and present in very low amounts.¹²³⁹ International regulatory authorities such as the World Health Organization and United States Food and Drug Administration set safety limits for how much residual DNA can be left in vaccines.¹²⁴⁰ Each batch of Comirnaty supplied in New Zealand undergoes residual DNA testing, and only batches that meet the specified safety limits are released for use.¹²⁴¹

Submitters pointed to some studies which claimed that the amount of DNA in the Comirnaty vaccine exceeds regulatory limits.¹²⁴² However, these claims are largely based on improper sample preparation techniques which fail to adequately remove spike protein mRNA, combined with the use of inappropriate tests which pick up both RNA and DNA but suggest that both are DNA.¹²⁴³ When the appropriate sample preparation techniques and tests are used, the detected levels of residual DNA are within the safety limits set by health authorities.¹²⁴⁴

For a residual DNA fragment to integrate into the human genome and cause cancer, it would first need to enter the cell nucleus where the DNA is stored. However, mRNA vaccines are specifically designed to deliver the mRNA to the cytoplasm – the outer part of the cell.¹²⁴⁵ If any residual DNA fragments were present and entered the cytoplasm along with the mRNA, they would be rapidly degraded by cellular enzymes that destroy unprotected linear DNA.¹²⁴⁶ It is very unlikely that any small residual DNA fragments would escape this degradation. However, even in the rare event that they did, integration into the genome would require the DNA to cross the nuclear membrane – a barrier that is normally extremely difficult to penetrate.¹²⁴⁷ Access may be more likely during cell division, when the nuclear membrane temporarily disassembles.¹²⁴⁸

Even if the fragment of DNA managed to enter the nucleus, it would then need to integrate into the chromosomal DNA. This process would usually require specific enzymes called integrases,¹²⁴⁹ which are not present in mRNA vaccines.¹²⁵⁰ Alternatively, it is theoretically possible that a DNA fragment could integrate at a double-stranded break in the DNA if the cell repairs the break using a pathway called non-homologous end joining (a quick method of joining DNA ends back together).¹²⁵¹ However, for this to be possible, the residual DNA fragment would need to be present exactly at the site of a break at exactly the time it was being repaired for it to be added in by mistake. This is highly improbable.

Furthermore, the DNA fragment would need to integrate in a way that specifically promotes cancer formation by disrupting a critical gene or regulatory region. This could involve activation of a proto-oncogene (a normal gene that helps cells grow, which can cause uncontrolled growth if it becomes overactive) or inactivation of a tumour suppressor gene (a gene that normally stops cells growing too fast or in the wrong way), but such activation and inactivation events are extremely rare.¹²⁵² In addition, most tumour suppressor genes require inactivation of both copies of the gene to have a negative effect¹²⁵³ and the development of most cancers requires the accumulation of multiple mutations,¹²⁵⁴ meaning that the likelihood of a residual DNA fragment causing cancer is highly improbable. Lastly, the cell with the harmful mutations would then need to evade the body’s immune system in order to cause cancer. Our immune system has multiple defence mechanisms designed to identify and destroy abnormal cells,¹²⁵⁵ which the cell would need to evade.

The substantial implausibility of each step of this process cumulatively means that the international consensus is that the risk of DNA integration and subsequent cancer development is considered negligible, and theoretical only.¹²⁵⁶ Vaccines (including several that contain DNA) have existed for decades and there is no evidence linking residual DNA in vaccines to cancer.¹²⁵⁷

1.1.2 Synthetic mRNA does not alter DNA | Kāore te mRNA hangahanga e whakarerekē i te DNA

As with DNA fragments, for the synthetic mRNA in vaccines to modify a vaccinated person’s genes, it would need to enter the cell, then the nucleus, then the chromosomal DNA, and alter the DNA in specific ways that cause cancer, while avoiding degradation by cellular enzymes. The mutated cell would then need to evade attacks from the body’s immune system. As outlined above, there are multiple biological barriers to prevent this from occurring. The evidence shows that mRNA is present temporarily¹²⁵⁸ to instruct cells to produce the spike protein to train the immune system to respond to future SARS-CoV-2 infections.¹²⁵⁹

Furthermore, mRNA itself cannot integrate into DNA – it must first be converted into DNA. The process of converting mRNA into DNA (‘reverse transcription’) requires a special enzyme called a reverse transcriptase. This enzyme is not part of the mRNA vaccine.¹²⁶⁰ Therefore, any conversion would depend on enzymes already present in the body.

The most likely biologically plausible mechanism for the synthetic mRNA to be turned into DNA and integrated into chromosomal DNA is through the activity of LINE-1 retrotransposons. These are genetic elements in the human genome that can copy and insert themselves into different parts of the human genome via an RNA intermediate. Most are inactive, but some are capable of mobilisation.¹²⁶¹ While they usually only reverse transcribe their own RNA, it is theoretically possible that they could reverse transcribe the RNA of the COVID-19 virus or vaccine and integrate into the genome.

Some peer-reviewed studies have examined this theoretical possibility, two of which were brought to the Inquiry’s attention by submitters.¹²⁶² The first of those studies reported that the mRNA from the COVID-19 virus (not the vaccine) can rarely integrate into human DNA. That study has been the subject of criticism and controversy for improper experimental design, interpretation of the results and failure to consider other plausible explanations for the data.¹²⁶³

The other study looked at reverse transcription of the Comirnaty vaccine into cells and suggested that the vaccine’s mRNA could be reversetranscribed into DNA. It shows some data to suggest involvement of LINE-1 in this process. There are several limitations to this study and the conclusions that can be drawn from it. First, the authors do not show that the reverse-transcribed DNA enters the nucleus or integrates into the genome. This has been frequently misrepresented, prompting the authors to release a statement addressing the misconceptions about their paper.¹²⁶⁴ Second, the findings were observed in cancer cells in petri dishes under experimental conditions, which are not representative of normal, healthy human cells. There is no evidence that the process can be replicated in healthy cells, in animal models or in genomes of vaccinated individuals.

Overall, there is no scientific evidence that mRNA from COVID-19 mRNA vaccines can integrate into host genomes and alter DNA. Ongoing monitoring has not established a link between mRNA vaccination and cancer.¹²⁶⁵

1.1.3 The SV40 promoter does not raise safety concerns | Kāore te kaiakiaki SV40 e whakaara ana i te āwangawanga haumaru

Submitters raised concerns about a SV40 promoter (a small piece of DNA used to produce the mRNA in the Comirnaty vaccine) being present in high concentrations in the Comirnaty vaccine and causing cancer in vaccinated individuals. They cited studies in support of their claims, discussed above and below.

SV40, which stands for Simian Virus 40, is a naturally-occurring DNA virus originating in monkeys. It was first discovered in 1960 in the monkey kidney cells that were used to produce polio vaccines. Early studies on SV40 showed that it could cause cancer in some animals,¹²⁶⁶ but whether SV40 causes human cancer has not been proven.¹²⁶⁷

The Comirnaty COVID-19 vaccine does not contain the SV40 virus.¹²⁶⁸ However, small pieces of DNA derived from the SV40 virus are used in the plasmid template used to make the vaccine’s mRNA.¹²⁶⁹ Such SV40 DNA components are commonly used in plasmids for biotechnology and medicine.¹²⁷⁰ Importantly, this DNA does not make any SV40 proteins, including the T-antigen protein, which is the part of SV40 linked to cancer.¹²⁷¹ This protein is not present in the Comirnaty vaccine.¹²⁷²

The SV40 DNA that is used for the manufacture of the Comirnaty vaccine is called a promoter – a short DNA sequence that helps ‘turn on’ genes. Additionally, the DNA plasmid used to manufacture the Comirnaty vaccine contains other SV40 derived DNA components – the SV40 ‘origin of replication’ (starting point for replicating DNA) and the PolyA signal (involved in mRNA processing).¹²⁷³ All three elements are considered non-functional in the vaccine itself and are not considered a safety risk.¹²⁷⁴

In addition, there is no reliable evidence that the amount of SV40 promoter in the vaccine goes above the safety limits set by regulators.¹²⁷⁵ As discussed above, studies put forward by submitters in support of these claims used expired or incorrectly stored vials and inappropriate sample preparation techniques and tests.¹²⁷⁶ During the vaccine-making process, any SV40 promoter DNA (and, as outlined above, any other residual DNA) that might be present gets broken down and ends up in very tiny amounts in the final product.¹²⁷⁷

Submitters raised concerns that the SV40 promoter is a cancer-causing gene (oncogene). However, the study referenced by submitters in support of this claim ¹²⁷⁸ is a general review of the SV40 virus and cancer – it does not say that the SV40 promoter alone (without the rest of the virus) causes cancer. While integration of the SV40 promoter or other SV40 elements into the chromosomal DNA could theoretically promote cancer, the risk from residual DNA fragments is considered negligible as several implausible events would need to occur, as discussed above.

Submitters also pointed to blog posts, rather than scientific studies, to support their claims about findings of SV40 DNA in vaccinated people’s blood or tumours.¹²⁷⁹ Those sources are not peer-reviewed and make claims which are not supported by peer-reviewed scientific evidence. For example, there is no compelling evidence to support the claim that the SV40 ‘origin of replication’ can replicate on its own;¹²⁸⁰ it requires the T-antigen protein¹²⁸¹ which, as discussed above, is not present in the vaccine. In addition, one of the blog posts¹²⁸² claims that the DNA is both highly fragmented and capable of replicating in cells, but these statements are contradictory because highly fragmented DNA cannot replicate. Therefore, these blog posts do not present reliable or compelling evidence of harm from the SV40 DNA.

Pfizer included the full plasmid sequence, including the SV40 elements, in its documents to regulators, although the non-functional SV40 elements were not highlighted initially,¹²⁸³ raising safety concerns among submitters. However, international regulatory agencies have all said that the SV40-derived DNA sequences in the vaccine are not a safety risk as they are not oncogenes, nor do they promote integration into chromosomal DNA.¹²⁸⁴

Because Comirnaty does not modify genes, it is not regulated as a gene therapy | Nā te mea kāore te Comirnaty e whakarerekē i ngā ira, kāore e waeturehia hei rongoā ira

A ‘gene therapy’ is a medicine that modifies a person’s genes to treat or cure a disease.¹²⁸⁵ A gene therapy is a different concept from a ‘genetically modified organism’ but was, at times, used interchangeably by submitters. As outlined in Chapter 2.1, Section 2.1.2.4, the Environmental Protection Authority decided that the Comirnaty vaccine did not meet the legal definition of a genetically modified organism.¹²⁸⁶ At the time of the COVID-19 pandemic, vaccines and medicines that could be considered gene therapies were both regulated by Medsafe under the Medicines Act 1981.¹²⁸⁷

Human gene therapy, as defined by the United States Food and Drug Administration,¹²⁸⁸ seeks to ‘modify or manipulate the expression of a gene or to alter the biological properties of living cells for therapeutic use. Gene therapy is a technique that modifies a person’s genes to treat or cure disease’.¹²⁸⁹ The United States Food and Drug Administration ‘generally considers human gene therapy products to include all products that mediate their effects by transcription or translation of transferred genetic material or by specifically altering host (human) genetic sequences’.¹²⁹⁰

While the mechanism of mRNA vaccines shares some similarities to parts of the United States Food and Drug Administration definition, vaccines against infectious diseases are specifically excluded from regulatory guidance for gene therapies in the United States and Europe.¹²⁹¹ Gene therapy products and mRNA vaccines against infectious diseases have different intents – gene therapy products aim to restore, correct, modify or replace a person’s genes to treat or cure a disease, whereas vaccines against infectious diseases aim to train the immune system to prevent infection of a bacterial or viral pathogen.¹²⁹² No regulatory authority globally classifies any mRNA vaccine against an infectious disease as a gene therapy.¹²⁹³

1.2 While there was a change in the manufacturing process for Comirnaty, this did not affect the vaccine’s safety or efficacy | Ahakoa i whakarerekēhia te tukanga whakaputa o te Comirnaty, kāore tēnei i pā ki te haumaru, ki te whaihua rānei o te werohanga

The manufacturing process for the Comirnaty vaccine changed when production was scaled up.¹²⁹⁴ The first process (Process 1) was used to produce the vaccines used in the clinical trials. The second process (Process 2) was used to produce the vaccines for commercial sale. Submitters expressed concern that the vaccine produced through Process 2 did not undergo clinical trials. They say that Process 2 vaccines had significantly lower mRNA integrity – meaning they contain less intact mRNA and more broken mRNA fragments (and excess DNA contamination, which has already been addressed above). Submitters were concerned these changes in mRNA integrity would affect how well the vaccine worked and might lead to the production of shortened forms of the spike protein, posing a potential safety risk.

To make the Comirnaty vaccine at a commercial scale, Pfizer had to adjust how the mRNA part of the vaccine was produced. These changes were not about altering the vaccine itself, but about making the process more efficient and suitable for large-scale manufacturing.

Originally, the DNA used to make the mRNA was created using a method called Polymerase Chain Reaction (PCR) – a laboratory technique that works well for small batches. For mass production, they switched to a method that uses bacteria (Escherichia coli) to grow the DNA as plasmids.¹²⁹⁵ This approach is widely used in the pharmaceutical industry because it is a more cost-effective and efficient way of producing sufficient DNA quantities for mass vaccine production.¹²⁹⁶ Once the bacteria grow the plasmids, the DNA is extracted and prepared for the next step.

Both Process 1 and Process 2 used a method called in vitro transcription to turn the DNA into mRNA although, as discussed below, this method was slightly adjusted¹²⁹⁷ in Process 2 to ensure it produced comparable mRNA integrity as in Process 1. In both cases, an enzyme called ‘DNase I’ was used to break down any leftover DNA after the mRNA was made.¹²⁹⁸

What did change between the processes was how the mRNA was ‘cleaned up’. In the earlier method, magnetic beads were used to separate the mRNA from other materials, such as enzymes and broken-down DNA. In the newer method, an enzyme called ‘Proteinase K’ was added to break down the leftover proteins, and then the mRNA was purified using a filtering technique.¹²⁹⁹This newer method is better suited for producing large quantities of vaccine.

Process 2 also improved how the lipid nanoparticles – the tiny fat bubbles that carry the mRNA into cells – were made, allowing for larger batches to be produced more efficiently.¹³⁰⁰

In order to gain regulatory approval for their vaccine, Pfizer had to demonstrate that the vaccines produced via Process 2 were comparable to those produced via Process 1. To do this, they performed a number of tests to produce comparability data.¹³⁰¹

Regulatory authorities around the world, including Medsafe, reviewed that data.¹³⁰² The European Medicines Agency observed a decrease in RNA integrity in initial Process 2 batches and requested further data. As a result, Pfizer adjusted Process 2 to produce RNA integrity levels that were more similar to those produced via Process 1.¹³⁰³ The European Medicines Agency concluded that this issue was satisfactorily addressed at the time of its conditional authorisation in December 2020.¹³⁰⁴

Nonetheless, regulatory authorities continued to closely monitor comparability through some of the conditions imposed on these initial provisional approvals.¹³⁰⁵ Medsafe was satisfied that the data provided in response validated the manufacturing process.¹³⁰⁶ There is no compelling evidence that Process 2 resulted in any significant differences that could potentially affect safety or efficacy.¹³⁰⁷

1.3 Although clinical trials were still ongoing, the vaccines were not ‘experimental’ when they were approved | Ahakoa i haere tonu ngā whakamātau haumanu, ehara ngā werohanga i te whakamātautau i te wā i whakaaetia ai

Submitters expressed concern that the vaccines were still ‘experimental’ at the time they began to be used because clinical trials to test their safety and efficacy were ongoing. They claimed that approving COVID-19 vaccines with only two months’ safety data was far below the standard two to three years normally required for vaccine approval and meant the safety and efficacy of the vaccines was unacceptably uncertain.

There is no fixed amount of data or length of trial necessary to gain approval of a vaccine.¹³⁰⁸ Instead, as discussed in Chapter 2.1, Section 2.1.2, regulatory authorities evaluate available evidence and grant approval based on careful review of the vaccine’s risks and benefits.¹³⁰⁹

Clinical trials for vaccine development usually take several years to complete and a lot of data is collected, some of which is ‘complete’ before the trial has ended.¹³¹⁰For example, assessing how many participants >developed symptomatic disease within a few months of vaccination may be completed within about six months if participant recruitment is fast, but assessment of immunity 12 months after vaccination obviously requires a longer follow-up period.

Clinical trials are designed with ‘primary endpoints’ which are the basis for determining whether the study has met its objective and are usually the main data evaluated for regulatory approval.¹³¹¹ ‘Secondary endpoints’ are those that provide supportive information about a vaccine’s effect on the primary endpoint or demonstrate additional effects on the disease.¹³¹²

The length of a clinical trial will vary depending on the endpoints, and on the characteristics of the disease. For example, clinical trials for tuberculosis vaccines usually have three years of follow-up to determine protection against symptomatic disease, as most people develop the disease within two years of exposure; this requires long trials to detect cases.¹³¹³ In contrast, for diseases like COVID-19 where people develop symptoms soon after exposure,¹³¹⁴ protection can be determined in shorter trials, although duration of protection will require longer follow-up.¹³¹⁵

Furthermore, as part of standard post-approval monitoring, regulatory bodies can require manufacturers to carry out studies that complement the efficacy data obtained in clinical trials before the vaccine was authorised.¹³¹⁶ These later studies collect effectiveness data to give additional information on, for example, long-term protection, the need for and timing of booster doses, or on the effectiveness of a vaccine in different populations or against new variants.¹³¹⁷

Continued monitoring post-approval does not mean that the vaccines are ‘experimental’.¹³¹⁸ Rather, this serves to increase knowledge of how the vaccine works in the real world. Ongoing monitoring occurs even for fully approved products as even large clinical trials are not large enough to identify extremely rare side effects.¹³¹⁹

That said, when a new vaccine is approved, there would normally be more than two months of clinical trial follow-up data to track safety and efficacy, which is what there was for the COVID-19 vaccines at the time of their initial approval. However, the decisions to provide initial approval of COVID-19 vaccines were based on careful review of their benefits and potential risks in the context of an ongoing health crisis. For COVID-19, the United States Food and Drug Administration released guidance that data from Phase III studies to support an Emergency Use Authorization would need a median followup duration of at least two months.¹³²⁰ This timeframe was used because adverse events considered plausibly linked to vaccination generally start within six weeks after vaccine receipt.¹³²¹ In terms of efficacy, a median of two months was considered the shortest follow-up period required to achieve some confidence that any protection against COVID-19 was likely to be more than very short-lived.¹³²² As we have outlined in Chapter 2.1, Section 2.1.2, this was reflected in advice Medsafe received about the Comirnaty vaccine.

With the Comirnaty vaccine, the ‘primary endpoints’¹³²³ findings from the Phase II/III part of the global combined Phase I/II/III trial were used to apply to the United States Food and Drug Administration in November 2020¹³²⁴ for Emergency Use Authorization while collection of ‘secondary endpoints’¹³²⁵ data was ongoing.¹³²⁶ This data was similarly available to Medsafe when it gave provisional consent in February 2021, with further data expected in April 2021. We have addressed in Chapter 2.1, Section 2.1.3 why we consider that the information available to Medsafe was sufficient in the circumstances, and why data on approval will usually – if not always – be limited depending on the design of the clinical trial.¹³²⁷

The COVID-19 vaccines underwent rigorous testing in large clinical trials – more than 40,000 participants for the Comirnaty clinical trial, which is larger than average.¹³²⁸ The vaccines also met or exceeded internationally-agreed benchmarks for safety and efficacy at their primary endpoints.¹³²⁹ The expert scientific consensus is that the COVID-19 vaccines were no longer considered ‘experimental’ once the primary endpoints in their clinical trials were completed and regulators authorised the vaccines for use.¹³³⁰ At that point, the trials had demonstrated satisfactory evidence of safety and efficacy.

1.4 There were adverse side effects from the vaccines, but they were recognised and acted upon appropriately | I puta ētahi pānga kino i ngā werohanga, engari i tautohua, ā, i whakautua tikatia

All medicines have side effects.¹³³¹ Describing a medicine as ‘safe’ does not mean that it is without risk. We have explained in Chapter 2.1, Sections 2.1.2 and 2.1.3 that we consider Medsafe had sufficient information to be satisfied that the benefits of Comirnaty outweighed its risks at the time it received provisional consent. We have noted that it is common to have limited data at the time a medicine is approved, because it has only been tested on small groups at that point. Rare or delayed adverse effects usually only become known once a medicine begins to be widely used.

Submitters raised concerns about the high number of adverse events reported following vaccination with the COVID-19 mRNA vaccine. They point to the high number of reports of adverse events as evidence that the vaccine is not safe.

As we have discussed in Chapter 2.1, Section 2.1.6, these statements show a misunderstanding of the pharmacovigilance system of reporting adverse events. A person’s report or experience of an adverse event after vaccination does not automatically mean that the vaccine caused the adverse event. It is therefore misleading to argue that the number of reports provides evidence about the frequency, severity or rates of problems associated with the vaccine.¹³³²

Anyone can submit a report of an adverse event and, in a large, populationwide rollout of a vaccine, many adverse events will occur coincidentally after vaccination.¹³³³ Reports can be inaccurate, incomplete, coincidental and unverifiable, or relate to a minor or expected adverse event that does not require further action.¹³³⁴ Every report of an adverse event must be assessed carefully by experts against internationally-recognised scientific criteria to determine the cause.¹³³⁵

As we have highlighted in Chapter 2.1, Section 2.1.7, some new risks emerged for the COVID-19 vaccines, including the risk of myocarditis and pericarditis associated with the Comirnaty vaccine. Those risks were managed by Medsafe, with support from the Centre for Adverse Reactions Monitoring and independent advice from the COVID-19 Vaccine Independent Safety Monitoring Board. Although under-reporting was a known issue with pharmacovigilance systems before COVID-19, the Ministry of Health took several steps to strengthen its system by encouraging reporting and introducing active surveillance (such as sending a survey to those who were recently vaccinated), in an effort to counter-balance the issue (discussed in Chapter 2.1, Section 2.1.6). We have seen no reliable evidence to indicate signals that were not detected or acted on appropriately.

The final report of the COVID-19 Vaccine Independent Safety Monitoring Board addresses the safety signals that arose and were assessed in respect of the COVID-19 vaccines used in New Zealand.¹³³⁶ We do not replicate that work, but address in further detail some of the submitters’ most prevalent concerns about vaccine adverse outcomes below.

1.4.1 There is no evidence that deaths from vaccines were incorrectly reported | Kāore he taunakitanga e tautoko ana i kōrero hē ngā matenga i honoa ki ngā werohanga

Submitters claimed that there has been a substantial increase in deaths following the rollout of the COVID-19 vaccines, and that the numbers of vaccine-related deaths officially reported were inaccurate.

As noted above, some people will die shortly after vaccination by chance, especially if they are elderly or have pre-existing conditions. For example, among 10 million vaccinated individuals, it can be predicted that 5.75 cases of ‘sudden death’ (defined as a natural, unexpected death within one hour of symptom onset, or if unwitnessed, within 24 hours of having been last seen alive and symptom-free) would coincidentally occur within six weeks of vaccination.¹³³⁷ Part of Medsafe’s process for assessing reports of adverse events includes comparing natural death rates to observed death rates following vaccination, to determine if there are any specific trends or patterns that might indicate a vaccine safety concern.¹³³⁸

All fatal reports received by the Centre for Adverse Reactions Monitoring for the COVID-19 vaccines were treated as serious, and provided to the COVID-19 Vaccine Independent Safety Monitoring Board for review and advice.¹³³⁹ As at 30 November 2022, 184 deaths had been reported to the Centre after the administration of the Comirnaty vaccine.¹³⁴⁰ At that stage, observed number of deaths reported after vaccination was less than the expected number of natural deaths.¹³⁴¹

At that time, following medical assessments, it was determined that:

163 deaths were unlikely to be related to the COVID-19 vaccine
15 deaths could not be assessed due to insufficient information
two cases were still under investigation
two deaths were determined by the Coroner to be due to myocarditis following the first dose of Comirnaty
one death was likely due to vaccine-induced myocarditis but was awaiting the Coroner’s determination
for one death, a link to the vaccine could not be excluded, myocarditis was found at the time of death (this death was awaiting the Coroner’s determination).¹³⁴²

The Coroner, whose role it is to investigate and, where possible, determine the cause of unexpected deaths, confirmed that as of August 2025, there had been a total of four deaths where a COVID-19 vaccine was implicated, either as a direct or indirect cause of the death.¹³⁴³

As of April 2025, the Accident Compensation Corporation, which has a different remit than the Coroner, had accepted five claims for a fatal injury related to a COVID-19 vaccine. Fewer than four claims for fatal injury have been declined, meaning that the total number of claims for fatal injury was less than 10.¹³⁴⁴

This data, which is similarly reflected overseas,¹³⁴⁵ shows that death is a very rare complication sadly experienced by a very small number of people following the rollout of the COVID-19 vaccines.

However, submitters referred to evidence showing excess mortality¹³⁴⁶ in 2022, attributable to the COVID-19 vaccines. In making this claim, submitters rely on a non-peer-reviewed 2022 paper, in which the author claims a close relationship between the time of the booster rollout and rising excess mortality.¹³⁴⁷

There are some important shortcomings with the analysis in this paper which affect the reliability of its conclusions. In particular, population changes were not considered.¹³⁴⁸ It does not account for the fact that New Zealand’s population has aged over the past decade,¹³⁴⁹ and people over 65 naturally have higher mortality.¹³⁵⁰ Failing to take that into account makes the number of ‘excess deaths’ look higher than it probably is.

Nor does the analysis consider other coinciding factors that could have caused the deaths, including the Omicron wave in 2022, changes in healthcare access, flu or other infectious outbreaks and delays in medical treatment due to the COVID-19 pandemic, all of which can contribute to excess mortality.¹³⁵¹ The study used population-level data for the number of excess deaths: this means that for any given death, it cannot be known what the cause of death was, whether the person had even had a booster, nor whether they had other health conditions. In this context, claiming a causal link between the timing of booster rollout and rising excess mortality is misleading.

A more rigorous, peer-reviewed study on COVID-19 mortality was published in 2025.¹³⁵² It used detailed data that accounted for age, sex, seasonality and changes in population size. It found that excess deaths in New Zealand from 2020 to 2023 were low overall and mostly linked to confirmed COVID-19 deaths in 2022–2023. In fact, there were fewer deaths than expected in 2020–2021 (encompassing the initial period of the vaccine rollout), likely due to low COVID-19 levels and fewer seasonal illnesses.

Submitters also cited peer-reviewed articles to support their concerns about excess mortality linked to the COVID-19 vaccines.¹³⁵³ However, for one of these articles,¹³⁵⁴ the journal issued an ‘Expression of Concern’ notice due to issues raised about the quality and messaging of the study.¹³⁵⁵ This notice also clarifies that the study does not provide any evidence to support the claim of a causal link between COVID-19 vaccination and mortality.

The second article is a review that claims to be peer-reviewed but is published in a journal that does not appear to meet recognised academic peer-review standards.¹³⁵⁶ The article relies on studies which have been retracted and contains several unsupported statements, such as claims of excess DNA contamination in the vaccines (addressed above). Neither of those articles therefore present convincing evidence of excess mortality attributable to the COVID-19 vaccines.

In summary, deaths following COVID-19 vaccination are rare. Attributing death to the vaccine requires causation – not just correlation – and ruling out other possible explanations. The majority of reported deaths have been found to be coincidental after vaccinating millions of people. There is no convincing evidence to support claims that the vaccines have caused excess deaths in New Zealand.

1.4.2 Comirnaty did not adversely affect pregnancy | Kāore te Comirnaty i pā kino ki te hapūtanga

Some submitters raised concerns about the safety of using the Comirnaty vaccine during pregnancy. They alleged that the government recommended it despite limited clinical trial data on its use in pregnant women, and said it caused increased pregnancy complications and infertility.

It is correct that, when Comirnaty received provisional approval from Medsafe, there was little data available on the risks in pregnant women.¹³⁵⁷ Nonetheless, Comirnaty was recommended for these women in consultation with their healthcare professionals. This led to concerns for pregnant women who were worried by the lack of reassuring data, and for healthcare professionals who were unsure how best to counsel their patients.

When questioned as to why Comirnaty was considered suitable for use in pregnant women, despite a lack of clinical trial data, the Ministry of Health said that the recommendation was based on the following considerations.

Pre-clinical animal studies had showed no vaccine-related effects on female fertility, pregnancy, embryo or foetal development, childbirth or postnatal development.
mRNA vaccines do not contain live virus, and there was no evidence or scientific rationale at the time to suggest increased risk for pregnant women based on the vaccine’s mechanism of action.
Other countries, such as Israel, had begun vaccinating pregnant women and the World Health Organization recommended a risk-based approach for vaccination in pregnancy, particularly for those at high risk of COVID-19 complications.
Excluding pregnant women would leave some of the population unprotected, which could impact the public health benefits of population-level protection from vaccination.
Potential risks and benefits could be managed and discussed on an individual level between health professionals and consumers, taking into account their specific circumstances.
Ongoing post-vaccination surveillance could identify emerging safety signals or outcomes in these groups.¹³⁵⁸

The Ministry’s point about the vaccine’s mechanism of action is particularly compelling. There are three ways submitters claimed that Comirnaty can adversely affect pregnancy. First, they claimed that mRNA vaccines damage the placenta. There is no compelling scientific rationale or evidence to support this claim. For example, the theory that mRNA vaccines generate antibodies that attack both the COVID-19 virus spike protein and a human protein called ‘syncytin-1’, which is important for forming the placenta during pregnancy, is unsupported. Although it is claimed that the spike protein and syncytin-1 are similar, there is in fact very little similarity between the two proteins¹³⁵⁹ and this small overlap is not enough to cause any problems with pregnancy or fertility.¹³⁶⁰ One study that compared the placentas of pregnant women in the United States who had received the COVID-19 vaccine with those who had not found no signs that the vaccine caused more placental lesions in the vaccinated group.¹³⁶¹

Second, some submitters claimed that lipid nanoparticles used to deliver the mRNA in the Comirnaty vaccine do not stay at the injection site as intended but instead spread throughout the body and accumulate in organs like the ovaries (biodistribution). These claims are based on animal studies performed on rats as part of the development of the Comirnaty vaccine. In those studies, researchers used radioactive tags as markers to track where the vaccine particles went in the body. The studies showed tiny amounts of the marker in various organs, which was acknowledged by regulatory authorities, including Medsafe, in their evaluation of the Comirnaty vaccine.¹³⁶²

Submitters claimed that this biodistribution data suggests that the spike protein might be produced in the ovaries, potentially causing damage to the ovaries and harming fertility. However, the animal studies only tracked the marker on the lipid nanoparticle; they did not conclude whether it was just the marker or the intact lipid nanoparticle, and whether the mRNA was there as well or if it caused any harm. Regulatory authorities reviewed the biodistribution data alongside other animal studies, which found no ovarian damage or negative reproductive or developmental effects, and concluded there were no safety concerns.¹³⁶³ This is consistent with studies in humans which have found that the mRNA vaccine has no increased risk on fertility or pregnancy, and causes no damage to the ovaries.¹³⁶⁴

Lastly, submitters pointed to numerous anecdotal reports about stillbirths and miscarriages after receiving the vaccine. We have noted above how correlation does not equate to causation. Between 10 and 20 percent of all pregnancies end with miscarriage: one study estimated that among 1 million vaccinated pregnant women, 397 can be predicted to have a miscarriage as coincident background cases within one day of vaccination.¹³⁶⁵

Overall, there is no scientific rationale or reliable evidence to support claims that mRNA vaccines cause infertility or miscarriage. The international consensus, supported by large-scale population studies, is that there is no association with adverse pregnancy outcomes or adverse effects on fertility.¹³⁶⁶

1.5 We can be reasonably confident that we now know the risks with the COVID-19 vaccines | Ka āhei te kī he tino mōhio tātou ki ngā mōrearea o ngā werohanga KOWHEORI-19’ i tēnei wā

Submitters were concerned that more evidence of harm from the vaccines will continue to show over time. Their concerns centre around the theories outlined above, claiming excess deaths or increases in cancer resulting from vaccination with Comirnaty.

Scientists cannot say with absolute certainty that no long-term effects will emerge years after Comirnaty vaccination. However, this is the case for any new medicine. No vaccine typically has 10 years of follow-up data before being authorised for widespread use. In many cases, it would be unethical to withhold a vaccine that has demonstrated safety and efficacy in clinical trials from those who need it, while waiting for such long-term data.¹³⁶⁷

As we have noted above, most adverse events that can be plausibly linked to vaccination generally show up within weeks or months.¹³⁶⁸ This was the case for Comirnaty, where rare cases of myocarditis usually occur within four days but, in a few cases, up to 14 days after receiving the vaccination.¹³⁶⁹ As of early 2026, Comirnaty has been used for more than five years: billions of doses have been administered and no delayed-onset adverse events have been observed.¹³⁷⁰ There is no strong or consistent evidence that Comirnaty causes excess deaths or cancer, although this continues to be monitored.¹³⁷¹

To support claims of unidentified long-term side effects, there must be plausible biological mechanisms for how this may occur. As we have discussed in this Appendix, there is currently no scientific explanation or evidence to support those concerns. For example, there is no rationale for long-term effects based on the way the Comirnaty vaccine works. The mRNA in the vaccine and the spike protein it produces are present temporarily before being destroyed. There is also no reliable evidence to suggest that the mRNA or any small amounts of residual DNA in the vaccines can integrate into a person’s genes and cause cancer. Nor is there any convincing evidence or plausible biological mechanism to support the vaccine causing infertility or adverse pregnancy-related outcomes. Therefore, while scientists cannot completely rule out the discovery of side effects in the future, there is currently no reason to expect this to occur.

¹²³⁷European Medicines Agency, Comirnaty Assessment Report (19 February 2021), https://www.ema.europa.eu/en/documents/assessment-report/comirnaty-epar-public-assessment-report_en.pdf, p16

¹²³⁸Norbert Pardi, Michael J. Hogan, Frederick W. Porter, and Drew Weissman, ‘mRNA vaccines – a new era in vaccinology’, Nat Rev Drug Discovery, 17, no. 4 (12 January 2018), https://doi.org/10.1038/nrd.2017.243

¹²³⁹Adam Achs, Tatiana Sedlackova, Lukas Predajna, Jaroslav Budis, Maria Bartosova, and others, ‘Systematic analysis of COVID-19 mRNA vaccines using four orthogonal approaches demonstrates no excessive DNA impurities’, npj Vaccines, 10, no. 259 (13 December 2025), https://doi.org/10.1038/s41541-025-01304-9

¹²⁴⁰U.S. Food & Drug Administration, ‘Guidance for Industry – Characterization and Quantification of Cell Substrates and Other Biological Materials Used in the Production of Viral Vaccines for Infectious Disease Indications’ (February 2010), https://www.fda.gov/media/78428/download

¹²⁴¹Ministry of Health, ‘H2023031858, Response to your request for official information’ (7 November 2023), https://www.health.govt.nz/system/files/2024-01/h2023031858_response.pdf

¹²⁴²Tyler J Wang, Alex Kim, and Kevin Kim, ‘A Rapid Detection Method of Replication-Competent Plasmid DNA from COVID-19 mRNA Vaccines for Quality Control’, Journal of High School Science, 8, no. 4 (29 December 2024), https://doi.org/10.64336/001c.127890 David J. Speicher, Jessica Rose, L. Maria Gutschi, David Wiseman, and Kevin McKernan, ‘DNA fragments detected in monovalent and bivalent Pfizer/BioNTech and Moderna modRNA COVID-19 vaccines from Ontario, Canada: Exploratory dose response relationship with serious adverse events’, OSF Preprints (19 October 2023), https://osf.io/preprints/osf/mjc97_v1 Kevin McKernan, Yvonne Helbert, Liam T. Kane, and Stephen McLaughlin, ‘Sequencing of bivalent Moderna and Pfizer mRNA vaccines reveals nanogram to microgram quantities of expression vector dsDNA per dose’, OSF Preprints (10 April 2023), https://osf.io/preprints/osf/b9t7m_v1

¹²⁴³Australian Government, Department of Health, Disability and Ageing, ‘Addressing misinformation about excessive DNA in the mRNA vaccines’ (18 October 2024), https://www.tga.gov.au/news/media-releases/addressing-misinformation-about-excessive-dna-mrna-vaccines Adam Achs, Tatiana Sedlackova, Lukas Predajna, Jaroslav Budis, Maria Bartosova, and others, ‘Systematic analysis of COVID-19 mRNA vaccines using four orthogonal approaches demonstrates no excessive DNA impurities’, npj Vaccines, 10, no. 259 (13 December 2025), https://doi.org/10.1038/s41541-025-01304-9 ThermoScientific, ‘T042-Technical Bulletin NanoDrop Spectrophotometers, 260/280 and 260/230 Ratios’, https://dna.uga.edu/wp-content/uploads/sites/51/2019/02/Note-on-the-260_280-and-260_230-Ratios.pdf

¹²⁴⁴Adam Achs, Tatiana Sedlackova, Lukas Predajna, Jaroslav Budis, Maria Bartosova, and others, ‘Systematic analysis of COVID-19 mRNA vaccines using four orthogonal approaches demonstrates no excessive DNA impurities’, npj Vaccines, 10, no. 259 (13 December 2025), https://doi.org/10.1038/s41541-025-01304-9 Stefanie Kaiser, Steffen Kaiser, Jenny Reis and Rolf Marschalek, ‘Quantification of objective concentrations of DNA impurities in mRNA vaccines’, Vaccine, 55, no 127022 (22 March 2025), https://doi.org/10.1016/j.vaccine.2025.127022 Australian Government, Department of Health, Disability and Ageing, Therapeutic Goods Administration, ‘Summary report of residual DNA and endotoxin on COVID-19 mRNA vaccines conducted by TGA laboratories’ (updated 5 August 2025), https://www.tga.gov.au/resources/publication/tga-laboratory-testing-reports/summary-report-residual-dna-and-endotoxin-covid-19-mrna-vaccines-conducted-tga-laboratories

¹²⁴⁵Namit Chaudhary, Drew Weissman, and Kathryn A. Whitehead, ‘mRNA vaccines for infectious diseases: principles, delivery and clinical translation’, Nature Reviews Drug Discovery, 20, 817–838 (25 August 2021), https://doi.org/10.1038/s41573-021-00283-5

¹²⁴⁶Sean R. Simpson, Wayne O. Hemphill, Teesha Hudson, and Fred W. Perrino, ‘TREX1 – Apex predator of cytosolic DNA metabolism’, DNA Repair, 94 (October 2020), https://doi.org/10.1016/j.dnarep.2020.102894 D. Lechardeur, K-J Sohm, M Haardt, PB Joshi, M Monck, and others, ‘Metabolic instability of plasmid DNA in the cytosol: a potential barrier to gene transfer’, Gene Therapy, 6 (7 April 1999), https://doi.org/10.1038/sj.gt.3300867

¹²⁴⁷Geoffrey M. Cooper, ‘The Nuclear Envelope and Traffic between the Nucleus and Cytoplasm’ in The Cell: A Molecular Approach. 2nd edition, Sinauer Associates, Sunderland, MA (2000), https://www.ncbi.nlm.nih.gov/books/NBK9927/

¹²⁴⁸AP Lam and DA Dean, ‘Progress and prospects: nuclear import of nonviral vectors’, Gene Therapy, 17 (4 March 2010), https://doi.org/10.1038/gt.2010.31

¹²⁴⁹An integrase is an enzyme some viruses use to insert themselves into cellular DNA.

¹²⁵⁰U.S. Food & Drug Administration, ‘Package Insert and Patient Package Insert – COMIRNATY’ (August 2025), https://www.fda.gov/media/151707/download, pp 26-27

¹²⁵¹Howard H.Y. Chang, Nicholas R. Pannunzio, Noritaka Adachi, and Michael R. Lieber, ‘Non-homologous DNA end joining and alternative pathways to double-stranded break repair’, Nat Rev Mol Cell Biol, 18, 459–506 (17 May 2017), https://doi.org/10.1038/nrm.2017.48 Susumu Ilizumi, Aya Kurosawa, Sairei So, Yasuyuki Ishii, Yuichi Chikaraishi, and others, ‘Impact of nonhomologous end-joining deficiency on random and targeted DNA integration: implications for gene targeting’, Nucleic Acids Research, 36, no. 19 (3 October 2008), https://doi.org/10.1093/nar/gkn649

¹²⁵²Bert Vogelstein, Nickolas Papadopoulos, Victor E. Velculescu, Shibin Zhou, Luis A, Dias, and Kenneth W. Kinzler, ‘Cancer Genome Landscapes’, Science, 339, no. 6127 (29 March 2013), https://doi.org/10.1126/science.1235122

¹²⁵³Li-Hui Wang, Chun-Fu Wu, Nirmal Rajasekaran, and Young Kee Shin, ‘Loss of Tumor Suppressor Gene Function in Human Cancer: An Overview’, Cellular Physiology and Biochemistry, 51, no. 6 (12 December 2018), https://doi.org/10.1159/000495956

¹²⁵⁴Bert Vogelstein, Nickolas Papadopoulos, Victor E. Velculescu, Shibin Zhou, Luis A, Dias, and Kenneth W. Kinzler, ‘Cancer Genome Landscapes’, Science, 339, no. 6127 (29 March 2013), https://doi.org/10.1126/science.1235122

¹²⁵⁵Gavin. P. Dunn, Lloyd J. Old, and Robert D. Schrieber, ‘The Three Es of Cancer Immunoediting’, Annu. Rev. Immunol., 22 (2004), https://doi.org/10.1146/annurev.immunol.22.012703.104803

¹²⁵⁶Harry Yang, Lanju Zhang, and Mark Galinski, ‘A probabilistic model for risk assessment of residual host cell DNA in biological products’, Vaccine, 28, no. 19 (26 April 2010), https://doi.org/10.1016/j.vaccine.2010.02.099 Brian J. Ledwith, Sujata Manam, Philip J. Trolio, Amy B. Barnum, Cindy J. Pauley, and others, ‘Plasmid DNA Vaccines: Investigating Integration into Host Cellular DNA following Intramuscular Injection in Mice’, Intervirology, 43, 4–6 (28 February 2001), https://doi.org/10.1159/000053993 D.E. Wuerenga, J. Cogan, and J.C. Petricciani, ‘Administration of Tumor Cell Chromatin to Immunosuppressed and Non-immunosuppressed Non-human Primates’, Biologicals, 23, no. 3 (September 1995), https://doi.org/10.1006/biol.1995.0036

¹²⁵⁷Australian Government, Department of Health, Disability and Ageing, ‘Addressing misinformation about excessive DNA in the mRNA vaccines’ (18 October 2024), https://www.tga.gov.au/news/media-releases/addressing-misinformation-about-excessive-dna-mrna-vaccines National Cancer Institute, ‘COVID-19 Vaccines and People with Cancer’ (10 October 2023), https://www.cancer.gov/about-cancer/coronavirus/covid-19-vaccines-people-with-cancer

¹²⁵⁸Edward Yang, Erik van Nimwegen, Michaela Zolan, Nikolaus Rajewsky, Mark Shroeder, and others, ‘Decay Rates of Human mRNAs: Correlation With Functional Characteristics and Sequence Attributes’, Genome Res., 13, no. 8 (August 2003), https://doi.org/10.1101/gr.1272403

¹²⁵⁹Medsafe, response to OIA request H2023024241 (24 May 2023), https://www.health.govt.nz/system/files/2023-05/h2023024241_response.pdf, p 16 Tudor Emanuel Fertig, Leona Chitoiu, Daciana Silva Marta, Victor-Stefan Ionescu, Valeriu Bodgan Cismasiu, and others, ‘Vaccine mRNA can be detected in blood at 15 days post-vaccination’, Biomedicines, 28, no. 7 (28 June 2022), https://doi.org/10.3390/biomedicines10071538 Aram J. Krauson, Faye Victoria C. Casimero, Zakir Siddiquee, and James R. Stone, ‘Duration of SARSCoV-2 mRNA vaccine persistence and factors associated with cardiac involvement in recently vaccinated patients’, npj Vaccines, 8, no. 141 (27 September 2023), https://doi.org/10.1038/s41541-023-00742-7

¹²⁶⁰U.S. Food & Drug Administration, ‘Package Insert and Patient Package Insert – COMIRNATY’ (August 2025), https://www.fda.gov/media/151707/download, pp 26–27

¹²⁶¹Haig H. Kazazian Jr and John V. Moran, ‘Mobile DNA in Health and Disease’, New England Journal of Medicine, 377, no. 4 (27 July 2017), https://www.nejm.org/doi/10.1056/NEJMra1510092

¹²⁶²Liguo Zhang, Alexsia Richards, M. Inmaculada Barrasa, Stephen H. Hughes, Richard A. Young, and Rudolf Jaenisch, ‘Reverse-transcribed SARS-CoV-2 RNA can integrate into the genome of cultured human cells and can be expressed in patient-derived tissues’, Proc. Natl. Acad. Sci. U.S.A., 118, no. 21 (2021), https://www.pnas.org/doi/full/10.1073/pnas.2105968118 Markus Aldén, Francisko Olofsson Falla, Daowei Yang, Mohammad Barghouth, Cheng Luan, Magnus Rasmussen, and Yang De Marinis, ‘Intracellular Reverse Transcription of Pfizer BioNTech COVID-19 mRNA Vaccine BNT162b2 In Vitro in Human Liver Cell Line’, Curr. Issues Mol. Biol., 44, no. 3 (2022), https://www.mdpi.com/1467-3045/44/3/73

¹²⁶³Rhys Parry, Robert J. Gifford, Spyros Lytras, Stuart C. Ray, and Lachlan J.M. Coin, ‘No evidence of SARS-CoV-2 reverse transcription and integration as the origin of chimeric transcripts in patient tissues’, Proc. Natl. Acad. Sci. U.S.A., 118, no. 33 (2021), https://www.pnas.org/doi/full/10.1073/pnas.2109066118 Nicole Grandi, Enzo Tramontano, and Ben Berkhout, ‘Integration of SARS-CoV-2 RNA in infected human cells by retrotransposons: an unlikely hypothesis and old viral relationships’ Retrovirology, 18, no. 34 (2021), https://retrovirology.biomedcentral.com/articles/10.1186/s12977-021-00578-w

¹²⁶⁴Lund University, ‘Q&A: COVID-19 Vaccine study gains attention’ (10 March 2022), https://www.lunduniversity.lu.se/article/qa-covid-19-vaccine-study-gains-attention

¹²⁶⁵National Cancer Institute, ‘COVID-19 Vaccines and People with Cancer’ (10 October 2023), https://www.cancer.gov/about-cancer/coronavirus/covid-19-vaccines-people-with-cancer Letter from U.S. Food & Drug Administration to Dr. Ladapo (14 December 2023), https://www.fda.gov/media/174875/download Australian Government, Department of Health, Disability and Ageing, ‘Addressing misinformation about excessive DNA in the mRNA vaccines’ (18 October 2024), https://www.tga.gov.au/news/media-releases/addressing-misinformation-about-excessive-dna-mrna-vaccines Global Vaccine Data Network, ‘”Turbo Cancer” and mRNA: The myth that defies biology and physics’ (31 October 2024), https://ghostarchive.org/archive/GjKNd Cecila Acuti Martellucci, Angelo Capadici, Graziella Soldato, Matteo Fiore, Enrico Zauli, and others, ‘COVID-19 vaccination, all-cause mortality, and hospitalization for cancer: 30-month cohort study in an Italian province’, EXCLI J., 24, 690-707 (1 July 2025), https://doi.org/10.17179/excli2025-8400

¹²⁶⁶A.J. Girardi, B.H. Sweet, V.B. Slotnick and M.R. Hilleman, ‘Development of tumors in hamsters inoculated in the neonatal period with vacuolating virus, SV40’, Proc Soc Exp Biol Med, 109, no. 3 (March 1962), https://journals.sagepub.com/doi/abs/10.3181/00379727-109-27298

¹²⁶⁷John Charles Rotondo, Elisa Mazzoni, Ilaria Bononi, Mauro Tognon, and Fernanda Martini, ‘Association between Simian Virus 40 and Human Tumors’ Front Oncol., 29, no. 670 (2019), https://doi.org/10.3389/fonc.2019.00670

¹²⁶⁸U.S. Food & Drug Administration, ‘Package Insert and Patient Package Insert – COMIRNATY’ (August 2025), https://www.fda.gov/media/151707/download, pp 26-27

¹²⁶⁹European Medicines Agency, ‘Type II variation assessment report for Comirnaty’ (February 2024), https://www.ghr.agency/wp-content/uploads/2025/01/Anlage_Wundc_32_Ema_Chmp_21199_2024_Type_Ii_Variation_Assessment.pdf

¹²⁷⁰Adam J. Schieferecke, Nadia Kuxhausen Ralph, and David V. Schaffer, ‘The Application of DNA Viruses to Biotechnology’, Viruses, 17, no. 3 (14 March 2025), https://doi.org/10.3390/v17030414 Miguel G. Toscano, Jeroen van der Velden, Sybrand van der Werf, Machteld Odijk, Ana Roque, and others, ‘Generation of a Vero-Based Packaging Cell Line to Produce SV40 Gene Delivery Vectors for Use in Clinical Gene Therapy Studies’, Mol Ther Methods Clin Dev., 6, 124–134 (5 July 2017), https://doi.org/10.1016/j.omtm.2017.06.007

¹²⁷¹Michele Carbone, Paola Rizzo, Philip M. Grimely, Antonio Procopio, Daphne J.Y. Mew and others, ‘Simian virus-40 large-T antigen binds p53 in human mesotheliomas’ Nature Medicine, 3 (01 August 1997), https://doi.org/10.1038/nm0897-908

¹²⁷²U.S. Food & Drug Administration, ‘Package Insert and Patient Package Insert – COMIRNATY’ (August 2025), https://www.fda.gov/media/151707/download, pp 26–27

¹²⁷³European Medicines Agency, ‘Type II variation assessment report for Comirnaty’ (February 2024), https://www.ghr.agency/wp-content/uploads/2025/01/Anlage_Wundc_32_Ema_Chmp_21199_2024_Type_Ii_Variation_Assessment.pdf

¹²⁷⁴European Medicines Agency, ‘Type II variation assessment report for Comirnaty’ (February 2024), https://www.ghr.agency/wp-content/uploads/2025/01/Anlage_Wundc_32_Ema_Chmp_21199_2024_Type_Ii_Variation_Assessment.pdf

¹²⁷⁵FactCheck.org, ‘Posts Falsely Claim FDA “Required” to Take mRNA COVID-19 Vaccines Off Market Due to Adulteration’ (3 November 2023), https://www.factcheck.org/2023/11/scicheck-posts-falsely-claim-fdarequired-to-take-mrna-covid-19-vaccines-off-market-due-to-adulteration/

¹²⁷⁶Australian Government, Department of Health, Disability and Ageing, ‘Addressing misinformation about excessive DNA in the mRNA vaccines’ (18 October 2024), https://www.tga.gov.au/news/media-releases/addressing-misinformation-about-excessive-dna-mrna-vaccines

¹²⁷⁷Adam Achs, Tatiana Sedlackova, Lukas Predajna, Jaroslav Budis, Maria Bartosova, and others, ‘Systematic analysis of COVID-19 mRNA vaccines using four orthogonal approaches demonstrates no excessive DNA impurities’, npj Vaccines, 10, no. 259 (13 December 2025), https://doi.org/10.1038/s41541-025-01304-9

¹²⁷⁸Regis A. Vilchez and Janet S. Butel, ‘Emergent Human Pathogen Simian Virus 40 and Its Role in Cancer’, Clin Microbiol Rev., 17, no. 3 (1 July 2004), https://doi.org/10.1128/cmr.17.3.495-508.2004

¹²⁷⁹Nepetalactone Newsletter, ‘SV40 origin of replication in mammalian cells in absence of SV40 Large T-Antigen Substack’ (15 October 2024), https://anandamide.substack.com/p/sv40-origin-of-replication-in-mammalian Open Review, ‘Why SRA sleuthing is so valuable’ (11 December 2024), https://anandamide.substack.com/p/chakraborty-open-review

¹²⁷¹Nepetalactone Newsletter, ‘SV40 origin of replication in mammalian cells in absence of SV40 Large T-Antigen Substack’ (15 October 2024), https://anandamide.substack.com/p/sv40-origin-of-replication-inmammalian?utm_source=publication-search

¹²⁸⁰Nepetalactone Newsletter, ‘SV40 origin of replication in mammalian cells in absence of SV40 Large
T-Antigen Substack’ (15 October 2024), https://anandamide.substack.com/p/sv40-origin-of-replication-inmammalian?
utm_source=publication-search

¹²⁸¹Bruce W. Stillman and Yukov Gluzman, ‘Replication and supercoiling of simian virus 40 DNA in cell extracts from human cells’, Mol Cell Biol., 5, no. 8. (August 1985), https://doi.org/10.1128/mcb.5.8.2051-2060.1985 Bruce Stillman, Robert D. Gerald, Ronald A. Guggenhiemer, and Yukov Gluzman, ‘T antigen and template requirements for SV40 replication in vitro’, EMBO Journal, 4, no. 11 (November 1985), https://pubmed.ncbi.nlm.nih.gov/2998767/

¹²⁸²Nepetalactone Newsletter, ‘SV40 origin of replication in mammalian cells in absence of SV40 Large T-Antigen Substack’ (15 October 2024), https://anandamide.substack.com/p/sv40-origin-of-replication-inmammalian?utm_source=publication-search

¹²⁸³European Medicines Agency, ‘Type II variation assessment report for Comirnaty’ (February 2024), https://www.ghr.agency/wp-content/uploads/2025/01/Anlage_Wundc_32_Ema_Chmp_21199_2024_Type_Ii_Variation_Assessment.pdf FactCheck.org, ‘Posts Falsely Claim FDA “Required” to Take mRNA COVID-19 Vaccines Off Market Due to Adulteration’ (3 November 2023), https://www.factcheck.org/2023/11/scicheck-posts-falsely-claim-fdarequired-to-take-mrna-covid-19-vaccines-off-market-due-to-adulteration/

¹²⁸⁴Letter from U.S. Food & Drug Administration to Dr. Ladapo, 14 December 2023, https://www.fda.gov/media/174875/download European Medicines Agency, ‘Type II variation assessment report for Comirnaty’ (February 2024), https://www.ghr.agency/wp-content/uploads/2025/01/Anlage_Wundc_32_Ema_Chmp_21199_2024_Type_Ii_Variation_Assessment.pdf FactCheck.org, ‘Posts Falsely Claim FDA “Required” to Take mRNA COVID-19 Vaccines Off Market Due to Adulteration’ (3 November 2023), https://www.factcheck.org/2023/11/scicheck-posts-falsely-claim-fdarequired-to-take-mrna-covid-19-vaccines-off-market-due-to-adulteration/

¹²⁸⁵U.S. Food & Drug Administration, ‘What is Gene Therapy?’ (25 July 2018), https://www.fda.gov/vaccinesblood-biologics/cellular-gene-therapy-products/what-gene-therapy

¹²⁸⁶Environmental Protection Authority, Decision, APP204176 (11 February 2021), https://www.epa.govt.nz/assets/FileAPI/hsno-ar/APP204176/APP204176-Decision.pdf

¹²⁸⁷This is set to change under the Gene Technology Bill 2024, which sets up the Environmental Protection Authority to regulate gene technologies.

¹²⁸⁸Gene therapy is not explicitly defined in the New Zealand Medicines Act 1981.

¹²⁸⁹U.S. Food & Drug Administration, ‘Long Term Follow-Up After Administration of Human Gene Therapy Products; Guidance for Industry’ (January 2020), www.fda.gov/media/113768/download

¹²⁹⁰U.S. Food & Drug Administration, ‘Long Term Follow-Up After Administration of Human Gene Therapy Products; Guidance for Industry’ (January 2020), www.fda.gov/media/113768/download

¹²⁹¹‘COMMISSION DIRECTIVE 2009/120/EC of 14 September 2009 amending Directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use as regards advanced therapy medicinal products’ (14 September 2009), https://eur-lex.europa.eu/eli/dir/2009/120/oj U.S. Food & Drug Administration, ‘Long Term Follow-Up After Administration of Human Gene Therapy Products; Guidance for Industry’ (January 2020), www.fda.gov/media/113768/download Mathieu Guerriaud and Evelyne Kohli, ‘RNA-based drugs and regulation: Toward a necessary evolution of the definitions issued from the European Union legislation’, Front. Med, 9, (17 October 2022), https://doi.org/10.3389/fmed.2022.1012497

¹²⁹²Australian Government, Department of Health and Aged Care, Office of the Gene Technology Regulator, mRNA vaccines are not gene therapies (26 June 2024), https://www.ogtr.gov.au/sites/default/files/2024-06/mrna_covid_19_vaccines_are_not_gene_therapies.pdf

¹²⁹³Australian Government, Department of Health and Aged Care, Office of the Gene Technology Regulator, mRNA vaccines are not gene therapies (26 June 2024), https://www.ogtr.gov.au/sites/default/files/2024-06/mrna_covid_19_vaccines_are_not_gene_therapies.pdf European Medicines Agency, ‘COVID-19 vaccines: key facts’, https://www.ema.europa.eu/en/humanregulatory-overview/public-health-threats/coronavirus-disease-covid-19/covid-19-medicines/covid-19-vaccines-key-facts U.S. Food & Drug Administration, ‘Approved Cellular and Gene Therapy Products’ (last updated 12 September 2025), https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-products ‘COMMISSION DIRECTIVE 2009/120/EC of 14 September 2009 amending Directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use as regards advanced therapy medicinal products’ (14 September 2009), https://eur-lex.europa.eu/eli/dir/2009/120/oj

¹²⁹⁴Fernando P. Polack, Stephen J. Thomas, Nicholas Kitchin, Judith Absalon, Alejandra Gurtman, and others, ‘Supplementary Information for “Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine”’, The New England Journal of Medicine, 383, no. 27 (10 December 2020), https://www.nejm.org/doi/suppl/10.1056/NEJMoa2034577/suppl_file/nejmoa2034577_protocol.pdf European Medicines Agency, Comirnaty Assessment Report (19 February 2021), https://www.ema.europa.eu/en/documents/assessment-report/comirnaty-epar-public-assessment-report_en.pdf, pp 17–19

¹²⁹⁵European Medicines Agency, Comirnaty Assessment Report (19 February 2021), https://www.ema.europa.eu/en/documents/assessment-report/comirnaty-epar-public-assessment-report_en.pdf, pp 17–19

¹²⁹⁶Ram Shankar, Marco Schmeer and Martin Schleef, ‘Producing Plasmid DNA Template for Clinical Grade RNA Vaccine Manufacture’ in Thomas Kramps (eds), RNA Vaccines: Methods and Protocols, Methods in Molecular Biology, Methods in Biology, vol. 2786, Humana, New York NY (2024), https://doi.org/10.1007/978-1-0716-3770-8_14

¹²⁹⁷This adjustment involved changing the volumes of ATP and CTP used in the in vitro transcription reaction. European Medicines Agency, Comirnaty Assessment Report (19 February 2021), https://www.ema.europa.eu/en/documents/assessment-report/comirnaty-epar-public-assessment-report_en.pdf, pp 17–19

¹²⁹⁸European Medicines Agency, Comirnaty Assessment Report (19 February 2021), https://www.ema.europa.eu/en/documents/assessment-report/comirnaty-epar-public-assessment-report_en.pdf, pp 17–19

¹²⁹⁹European Medicines Agency, Comirnaty Assessment Report (19 February 2021), https://www.ema.europa.eu/en/documents/assessment-report/comirnaty-epar-public-assessment-report_en.pdf

¹³⁰⁰Fernando P. Polack, Stephen J. Thomas, Nicholas Kitchin, Judith Absalon, Alejandra Gurtman, and others, ‘Supplementary Information for “Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine”’, The New England Journal of Medicine, 383, no. 27 (10 December 2020), https://www.nejm.org/doi/suppl/10.1056/NEJMoa2034577/suppl_file/nejmoa2034577_protocol.pdf

¹³⁰¹European Medicines Agency, Comirnaty Assessment Report (19 February 2021), https://www.ema.europa.eu/en/documents/assessment-report/comirnaty-epar-public-assessment-report_en.pdf, pp 17–19

¹³⁰²Medsafe, response to OIA request H202106950 (13 August 2021), https://www.health.govt.nz/system/files/2021-10/h202106950_-_response.pdf

¹³⁰³European Medicines Agency, Comirnaty Assessment Report (19 February 2021), https://www.ema.europa.eu/en/documents/assessment-report/comirnaty-epar-public-assessment-report_en.pdf, pp 17–19

¹³⁰⁴Serena Tinari, ‘The EMA covid-19 data leak, and what it tells us about mRNA instability’, BMJ, 372, no. 627 (2021), https://doi.org/10.1136/bmj.n627

¹³⁰⁵New Zealand Gazette, 2021-go338, Provisional Consent to the Distribution of a New Medicine (3 February 2021), https://gazette.govt.nz/notice/id/2021-go338 European Medicines Agency, Comirnaty Assessment Report (19 February 2021), https://www.ema.europa.eu/en/documents/assessment-report/comirnaty-epar-public-assessment-report_en.pdf, pp 36–40

¹³⁰⁶Conditions imposed as part of the initial provisional consent were met. New Zealand Gazette, 2021-go338, Provisional Consent to the Distribution of a New Medicine (3 February 2021), https://gazette.govt.nz/notice/id/2021-go338 New Zealand Gazette, 2021-go4666, Renewal of Provisional Consent to the Distribution of a Medicine (28 October 2021), https://gazette.govt.nz/notice/id/2021-go4666 New Zealand Gazette, 2023-go5223, Consent to the Distribution of New Medicines (15 November 2023), https://gazette.govt.nz/notice/id/2023-go5223

¹³⁰⁷Medicines and Healthcare products Regulatory Agency, Summary of the Public Assessment Report for COVID-19 Vaccine Pfizer/BioNTech, GOV.UK (December 2020), https://www.gov.uk/government/publications/regulatory-approval-of-pfizer-biontech-vaccine-for-covid-19/summary-public-assessmentreport-for-pfizerbiontech-covid-19-vaccine U.S. Food & Drug Administration, Emergency Use Authorization (EUA) for Pfizer-BioNTech COVID-19 Vaccine Review Memorandum (11 December 2020), https://www.fda.gov/media/144416/download European Medicines Agency, Comirnaty Assessment Report (19 February 2021), https://www.ema.europa.eu/en/documents/assessment-report/comirnaty-epar-public-assessment-report_en.pdf, pp 137–138

¹³⁰⁸World Health Organization, ‘Guidelines on Clinical Evaluation of Vaccines: Regulatory Expectations Replacement of Annex 1 of WHO Technical Report Series, No. 924’ (2016), https://cdn.who.int/media/docs/default-source/biologicals/vaccine-standardization/clinical-evaluation-of-vaccines/who_trs_1004_web_annex_9.pdf?sfvrsn=902cbb42_3&download=true European Medicines Agency, ‘Guideline on clinical evaluation of vaccines’ (16 January 2023), https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-clinical-evaluationvaccines-revision-1_en.pdf U.S. Food & Drug Administration, ‘Emergency Use Authorization of Medical Products and Related Authorities: Guidance for Industry and Other Stakeholders’ (January 2017), https://www.fda.gov/media/97321/download, p 14 Débora D. Gräf, Lukas Westphal, and Christine E. Hallgreen, ‘The life cycle of vaccines evaluated by the European Medicines Agency’, Vaccine, 42, no. 21 (30 August 2024), https://doi.org/10.1016/j.vaccine.2024.126186

¹³⁰⁹Medsafe,’Medsafe’s Evaluation and Approval Process’ (revised 12 September 2019), https://www.medsafe.govt.nz/Consumers/Safety-of-Medicines/Medsafe-Evaluation-Process.asp#Process

¹³¹⁰National Centre for Immunisation Research and Surveillance Australia, ‘Phases of clinical trials’ (last updated April 2023), https://ncirs.org.au/phases-clinical-trials

¹³¹¹National Center for Advancing Translational Sciences, ‘Toolkit for Patient-Focused Therapy Development. Endpoint’, https://toolkit.ncats.nih.gov/glossary/endpoint/

¹³¹²National Center for Advancing Translational Sciences, ‘Toolkit for Patient-Focused Therapy Development. Endpoint’, https://toolkit.ncats.nih.gov/glossary/endpoint/

¹³¹³Dereck R. Tait, Mark Hatherill, Oliver Van Der Meeren, Ann M. Ginsberg, Elana Van Brakel, and others, ‘Final Analysis of a Trial of M72/AS01E Vaccine to Prevent Tuberculosis’, New England Journal of Medicine, 381, no. 25 (28 October 2019), https://www.nejm.org/doi/full/10.1056/NEJMoa1909953

¹³¹⁴Fernando P. Polack, Stephen J. Thomas, Nicholas Kitchin, Judith Absalon, Alejandra Gurtman, and others, ‘Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine’, The New England Journal of Medicine, 383, no. 27 (10 December 2020), https://www.nejm.org/doi/full/10.1056/NEJMoa2034577

¹³¹⁵Philip R. Krause and Marion F. Gruber, ‘Emergency Use Authorization of Covid Vaccines – Safety and Efficacy Follow-up Considerations’, New England Journal of Medicine, 383, no. 19, (16 October 2020), https://www.nejm.org/doi/10.1056/NEJMp2031373

¹³¹⁶World Health Organization, ‘Guidelines on Clinical Evaluation of Vaccines: Regulatory Expectations; Replacement of Annex 1 of WHO Technical Report Series, No. 924’ (2016), https://cdn.who.int/media/docs/default-source/biologicals/vaccine-standardization/clinical-evaluation-of-vaccines/who_trs_1004_web_annex_9.pdf Débora D. Gräf, Lukas Westphal, and Christine E. Hallgreen, ‘The life cycle of vaccines evaluated by the European Medicines Agency’, Vaccine, 42, no. 21 (30 August 2024), https://doi.org/10.1016/j.vaccine.2024.126186

¹³¹⁷European Medicines Agency, ‘COVID-19 vaccines: development, evaluation, approval and monitoring’, https://www.ema.europa.eu/en/human-regulatory-overview/public-health-threats/coronavirusdisease-covid-19/covid-19-public-health-emergency-international-concern-2020-23/covid-19-vaccinesdevelopment-evaluation-approval-monitoring

¹³¹⁸Maxwell J. Smith and Ezekial J. Emanuel, ‘Learning from five bad arguments against mandatory vaccination’, Vaccine, 41, no. 21 (25 April 2023), https://doi.org/10.1016/j.vaccine.2023.04.046

¹³¹⁹Songal Singh and Yoon K. Loke, ‘Drug safety assessment in clinical trials: methodological challenges and opportunities’, Trials, 13, no. 138 (20 August 2012), https://doi.org/10.1186/1745-6215-13-138 Medsafe, ‘Adverse Reactions to Medicines and Vaccines’ (updated 21 November 2023), https://www.medsafe.govt.nz/consumers/safety-of-medicines/Medicine-safety.asp

¹³²⁰U.S. Food & Drug Administration, Emergency Use Authorization for Vaccines Explained (20 November 2020), https://www.fda.gov/vaccines-blood-biologics/vaccines/emergency-useauthorization-vaccines-explained

¹³²¹Philip R. Krause and Marion F. Gruber, ‘Emergency Use Authorization of Covid Vaccines – Safety and Efficacy Follow-up Considerations’, New England Journal of Medicine, 383, no. 19 (16 October 2020), https://www.nejm.org/doi/10.1056/NEJMp2031373 National Vaccine Injury Compensation Program, ‘Vaccine Injury Table’, Health Resources and Services Administration (2017), https://www.hrsa.gov/sites/default/files/hrsa/vaccine-compensation/vaccineinjury-table.pdf

¹³²²Philip R. Krause and Marion F. Gruber, ‘Emergency Use Authorization of Covid Vaccines – Safety and Efficacy Follow-up Considerations’, New England Journal of Medicine, 383, no. 19 (16 October 2020), https://www.nejm.org/doi/10.1056/NEJMp2031373 484 AOTEAROA NEW ZEALAND ROYAL COMMISSION OF INQUIRY COVID-19 LESSONS LEARNED • PHASE TWO MAIN REPORT

¹³²³For example, reports of adverse events and use of medications to reduce fever or pain after each dose of vaccine or placebo and the efficacy of the vaccine against confirmed COVID-19. Fernando P. Polack, Stephen J. Thomas, Nicholas Kitchin, Judith Absalon, Alejandra Gurtman and others, ‘Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine’, The New England Journal of Medicine, 383, no. 27 (10 December 2020), https://www.nejm.org/doi/full/10.1056/NEJMoa2034577

¹³²⁴Contagion Live Kevin Kunzmann, ‘FDA Authorizes Pfizer, BioNTech COVID-19 Vaccine for the US’ (12 December 2020), https://www.contagionlive.com/view/fda-authorizes-pfizer-biontech-covid-19-vaccine-us

¹³²⁵Major endpoints included the efficacy of the vaccine against severe COVID-19. Fernando P. Polack, Stephen J. Thomas, Nicholas Kitchin, Judith Absalon, Alejandra Gurtman, and others, ‘Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine’, The New England Journal of Medicine, 383, no. 27 (10 December 2020), https://www.nejm.org/doi/full/10.1056/NEJMoa2034577

¹³²⁶Fernando P. Polack, Stephen J. Thomas, Nicholas Kitchin, Judith Absalon, Alejandra Gurtman, and others, ‘Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine’, The New England Journal of Medicine, 383, no. 27 (10 December 2020), https://www.nejm.org/doi/full/10.1056/NEJMoa2034577

¹³²⁷Maha Salloum, Antea Paviotti, Hilde Bastiaens, and Jean-Pierre van Geertruydgen, ‘The inclusion of pregnant women in vaccine clinical trials: An overview of late-stage clinical trials’ records between 2018 and 2023’, Vaccine, 41, no. 48 (28 October 2023), https://doi.org/10.1016/j.vaccine.2023.10.057

¹³²⁸Fernando P. Polack, Stephen J. Thomas, Nicholas Kitchin, Judith Absalon, Alejandra Gurtman, and others, ‘Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine’, The New England Journal of Medicine, 383, no. 27 (10 December 2020), https://www.nejm.org/doi/full/10.1056/NEJMoa2034577 Steven H Weinberg, Amy T Butchart, and Matthew M. Davis, ‘Size of clinical trials and Introductory prices of prophylactic vaccine series’, Hum Vaccin Immunother. 8 no. 8 (2012), https://doi.org/10.4161/hv.20506

¹³²⁹World Health Organization, ‘Considerations for evaluation of COVID-19 vaccines: points to consider for manufacturers of COVID-19 vaccines’ (25 November 2020), https://cdn.who.int/media/docs/defaultsource/in-vitro-diagnostics/covid19/considerations-who-evaluation-of-covid-vaccine_v25_11_2020.pdf World Health Organization, ‘WHO Target Product Profiles for COVID-19 Vaccines, Version 3 (29 April 2020), https://www.who.int/docs/default-source/blue-print/who-target-product-profiles-for-covid-19-vaccines.pdf Fernando P. Polack, Stephen J. Thomas, Nicholas Kitchin, Judith Absalon, Alejandra Gurtman, and others, ‘Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine’, The New England Journal of Medicine, 383, no. 27 (10 December 2020), https://www.nejm.org/doi/full/10.1056/NEJMoa2034577

¹³³⁰Helen Petousis-Harris, ‘The eight most common myths about Covid vaccines’ (29 April 2021), https://newsroom.co.nz/2021/04/29/the-eight-most-common-myths-about-covid-vaccines/

¹³³¹Matthew P Doogue, ‘A safe and effective drug?’, N Z Med. J, 127, no. 1404 (17 October 2024), https://nzmj.org.nz/media/pages/journal/vol-127-no-1404/a-safe-and-effective-drug/f080d9f2aa-1696478466/a-safe-and-effective-drug.pdf

¹³³²U.S. Centers for Disease Control and Prevention, ‘About the Vaccine Adverse Event Reporting System (VAERS)’ (7 August 2024), https://www.cdc.gov/vaccine-safety-systems/vaers/index.html 486 AOTEAROA NEW ZEALAND ROYAL COMMISSION OF INQUIRY COVID-19 LESSONS LEARNED • PHASE TWO MAIN REPORT

¹³³³ Steven Black, Juhani Eskola, Claire-Anne Siegrist, Neal Halsey, Noni MacDonald, and others, ‘Importance of background rates of disease in assessment of vaccine safety during mass immunisation with pandemic H1N1 influenza vaccines’, The Lancet, 374, no. 9707 (2009), https://doi.org/10.1016/S0140-6736(09)61877-8

¹³³⁴ U.S. Centers for Disease Control and Prevention, ‘About the Vaccine Adverse Event Reporting System (VAERS)’ (7 August 2024), https://www.cdc.gov/vaccine-safety-systems/vaers/index.html

¹³³⁵ For example, the Centre for Adverse Reactions Monitoring uses the World Health Organization causality assessment criteria for this evaluation. University of Otago, ‘New Zealand Pharmacovigilance Centre and Centre for Adverse Reactions Monitoring’, https://nzphvc-carm.otago.ac.nz/home/Uppsala Monitoring Centre, ‘The use of the WHO-UMC system for standardised case causality assessment’, https://www.who.int/docs/default-source/medicines/pharmacovigilance/whocausality-assessment.pdf

¹³³⁶ COVID-19 Vaccine Independent Safety Monitoring Board, Final report 2022: COVID-19 Vaccine Independent Safety Monitoring Board (3 July 2023), https://www.tewhatuora.govt.nz/publications/finalreport-of-the-covid-19-vaccine-independent-safety-monitoring-board-cv-ismb

¹³³⁷ Christoper Sefton, Susan Keen, Caroline Tybout, Feng-Chang Lin, Huijan Jiang, and others, ‘Characteristics of sudden death by clinical criteria’, Medicine, 102, no. 16 (21 April 2023), https://doi.org/10.1097/MD.0000000000033029
Steven Black, Juhani Eskola, Claire-Anne Siegrist, Neal Halsey, Noni MacDonald, and others, ‘Importance of background rates of disease in assessment of vaccine safety during mass immunisation with pandemic H1N1 influenza vaccines’, The Lancet, 374, no. 9707 (2009), https://doi.org/10.1016/S0140-6736(09)61877-8

¹³³⁸ Medsafe, ‘How does Medsafe monitor vaccine safety?’ (revised 21 November 2023), https://www.medsafe.govt.nz/Consumers/Safety-of-Medicines/Vaccine-safety.asp Medsafe, ‘Adverse events following immunisation with COVID-19 vaccines: Safety Report #46 – 30 November 2022’ (14 December 2022), https://www.medsafe.govt.nz/COVID-19/safety-report-46asp#death

¹³³⁹ COVID-19 Vaccine Independent Safety Monitoring Board, Final report 2022: COVID-19 Vaccine Independent Safety Monitoring Board (3 July 2023), https://www.tewhatuora.govt.nz/publications/finalreport-of-the-covid-19-vaccine-independent-safety-monitoring-board-cv-ismb

¹³⁴⁰ There were no deaths reported for the Vaxzevria or Nuvaxovid vaccines.

¹³⁴¹ Medsafe, ‘Adverse events following immunisation with COVID-19 vaccines: Safety Report #46 – 30 November 2022’ (14 December 2022), https://www.medsafe.govt.nz/COVID-19/safety-report-46.asp#death

¹³⁴² Medsafe, ‘Adverse events following immunisation with COVID-19 vaccines: Safety Report #46 – 30 November 2022’ (14 December 2022), https://www.medsafe.govt.nz/COVID-19/safety-report-46.asp#death

¹³⁴³ Office of the Chief Coroner, response to production order issued by NZ Royal Commission of Inquiry into COVID-19 Lessons Learned: Phase Two under section 20 of the Inquiries Act 2013 (15 August 2025)

¹³⁴⁴ We have not sought to examine in detail the cause of the difference between the figures from the Coroner and ACC as this is not the role of the Inquiry. However, the organisations have different roles and required thresholds, which may explain the discrepancy. Accident Compensation Corporation, response to production order issued by NZ Royal Commission of Inquiry into COVID-19 Lessons Learned: Phase Two under section 20 of the Inquiries Act 2013 (03 April 2025)

¹³⁴⁵ For example, in Australia: ‘Since the beginning of the vaccine rollout to 29 October 2023, almost 69 million doses of COVID-19 vaccines have been given in Australia. The TGA has identified 14 reports where the cause of death was linked to vaccination from 1,004 reports received and reviewed.’ (All COVID-19 vaccines, not just Comirnaty)
Australian Government, Department of Health, Disability and Ageing, ‘COVID-19 vaccine safety report – 02-11-23’ (2 November 2023), https://www.tga.gov.au/news/covid-19-vaccine-safety-reports/covid-19-vaccine-safety-report-02-11-23

¹³⁴⁶ Excess mortality refers to the increase in the number of deaths occurring in a specific time period or population, compared to what would normally be expected based on historical data or reference period. It serves as a broader measure of a health crisis impact than just reported fatalities, as it captures all deaths above a projected baseline, including those indirectly caused by the event (such as deaths due to delays in diagnosis during a pandemic). Our World in Data, ‘Excess mortality during the Coronavirus pandemic (COVID-19)’ (revised 2024), https://ourworldindata.org/excess-mortality-covid

¹³⁴⁷John Gibson, ‘The Rollout of COVID-19 Booster Vaccines is Associated With Rising Excess Mortality in New Zealand’ (June 2022), https://repec.its.waikato.ac.nz/wai/econwp/2211_Gibson.pdf

¹³⁴⁸ Michael J. Plank, Pubudu Senanayake and Richard Lyon, ‘Estimating excess mortality during the Covid-19 pandemic in Aotearoa New Zealand’, International Journal of Epidemiology, 54, no. 4 (15 June 2025), https://doi.org/10.1093/ije/dyaf093
Daniel V. Viglo, Kristen L. Hudec, Siamoom Ferdous, Richard J. Muthali, Julia Pei, and others, ‘Excess mortality in COVID-19-negative people with non-communicable disorders during the first pandemic wave’, BMC Public Health, 25, no. 736 (22 February 2025), https://doi.org/10.1186/s12889-025-21782-9
Ursel Heudorf and Bernd Kowall, ‘Mortality in Frankfurt am Main, Germany, 2020–2023: higher excess mortality during an influenza wave in 2022 than during all COVID-19 waves altogether’, GMS Hyg Infect Control, 20 (4 March 2025), https://doi.org/10.3205/dgkh000533

¹³⁴⁹ Environmental Health Intelligence New Zealand, ‘Age Profile’, https://www.ehinz.ac.nz/indicators/population-vulnerability/age-profile/

¹³⁵⁰ Our World in Data, ‘Annual death rate per age group, United States, 2023’, https://ourworldindata.org/grapher/annual-death-rate-by-age-group

¹³⁵¹ Michael J. Plank, Pubudu Senanayake and Richard Lyon, ‘Estimating excess mortality during the Covid-19 pandemic in Aotearoa New Zealand’, International Journal of Epidemiology, 54, no. 4 (15 June 2025), https://doi.org/10.1093/ije/dyaf093

¹³⁵² Michael J. Plank, Pubudu Senanayake and Richard Lyon, ‘Estimating excess mortality during the Covid-19 pandemic in Aotearoa New Zealand’, International Journal of Epidemiology, 54, no. 4 (15 June 2025), https://doi.org/10.1093/ije/dyaf093

¹³⁵³ Saskia Mostert, Marcel Hoogland, Minke Huibers, and Gertjan Kaspers. ‘Excess mortality across countries in the Western World since the COVID-19 pandemic: “Our World in Data” estimates of January 2020 to December 2022’, BMJ Public Health (2024), https://doi.org/10.1136/bmjph-2023-000282
Nicolas Hulscher, Mary T. Bowden, and Peter A. McCullough. ‘Review: Calls for Market Removal of COVID-19 Vaccines Intensify as Risk Far Outweigh Theoretical Benefits’, Science, Public Health Policy, and the Law (2025), https://publichealthpolicyjournal.com/review-of-calls-for-market-removal-of-covid-19-vaccines-intensify-risks-far-outweigh-theoretical-benefits/

¹³⁵⁴ Saskia Mostert, Marcel Hoogland, Minke Huibers, and Gertjan Kaspers. ‘Excess mortality across countries in the Western World since the COVID-19 pandemic: “Our World in Data” estimates of January 2020 to December 2022’, BMJ Public Health (2024), https://doi.org/10.1136/bmjph-2023-000282

¹³⁵⁵ BMJ Publishing Group Ltd. ‘Expression of concern: Excess mortality across countries in the western world since the COVID-19 pandemic: ‘Our World in Data’ estimates of January 2020 to December 2022’, BMJ Public Health (2024), https://bmjpublichealth.bmj.com/content/2/1/e000282eoc

¹³⁵⁶ Nicolas Hulscher, Mary T. Bowden, and Peter A. McCullough. ‘Review: Calls for Market Removal of COVID-19 Vaccines Intensify as Risk Far Outweigh Theoretical Benefits’, Science, Public Health Policy, and the Law (2025), https://publichealthpolicyjournal.com/review-of-calls-for-market-removal-of-covid-19-vaccines-intensify-risks-far-outweigh-theoretical-benefits/

¹³⁵⁷ As well as immunocompromised and lactating individuals.

¹³⁵⁸ Ministry of Health, response to production order issued by NZ Royal Commission of Inquiry into COVID-19 Lessons Learned: Phase Two under section 20 of the Inquiries Act 2013 (16 June 2025)

¹³⁵⁹ Malgorzata Kloc, Ahmed Uosef, Jacek Z. Kubiak, and Rafik M. Ghobrial, ‘Exaptation of Retroviral Syncytin for Development of Syncytialized Placenta, Its Limited Homology to the SARS-CoV-2 Spike Protein and Arguments against Disturbing Narrative in the Context of COVID-19 Vaccination’, Biology (Basel), 10, no. 3 (19 March 2021), https://doi.org/10.3390/biology10030238

¹³⁶⁰ Alice Lu-Culligan, Alexandra Tabachnikova, Eddy Pérez-Then, Maria Tokuyama, Hannah J Lee, and others, ‘No evidence of fetal defects or anti-syncytin-1 antibody induction following COVID-19 mRNA vaccination’, PLoS Biol., 20, no. 5 (24 May 2022), https://doi.org/10.1371/journal.pbio.3001506

¹³⁶¹Elisheva D Shanes, Sebastian Otero, Leena B Mithal, Chiedza A Mupanomunda, Emily S Miller, and Jeffery A Goldstein, ‘Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccination in Pregnancy: Measures of Immunity and Placental Histopathology’, Obstetrics and gynecology, 138, no. 2 (2021), https://doi.org/10.1097/AOG.0000000000004457

¹³⁶² European Medicines Agency, Comirnaty Assessment Report (19 February 2021), https://www.ema.europa.eu/en/documents/assessment-report/comirnaty-epar-public-assessment-report_en.pdf, pp 47 and 54 Medsafe, response to OIA request H2023024241 (24 May 2023), https://www.health.govt.nz/system/files/2023-05/h2023024241_response.pdf, p 15

¹³⁶³ Medsafe, response to OIA request H2023024241 (24 May 2023), https://www.health.govt.nz/system/files/2023-05/h2023024241_response.pdf, pp 15 and 18 European Medicines Agency, Comirnaty Assessment Report (19 February 2021), https://www.ema.europa.eu/en/documents/assessment-report/comirnaty-epar-public-assessment-report_en.pdf, pp 47, 50 and 54

¹³⁶⁴ Smriti Prasad, Erkan Kalafat, Helena Blakeway, Rosemary Townsend, Pat O’Brien, and others, ‘Systematic review and meta-analysis of the effectiveness and perinatal outcomes of COVID-19 vaccination in pregnancy’, Nature Communications, 13, no. 2421 (10 May 2022), https://doi.org/10.1038/s41467-022-30052-w
Abdulrahman Ibrahim Hagrass, Hossam Waleed Almadhoon, Mohammed Al-kafarna, Bashar Khaled Almaghary, Anas Zakarya Nourelden, and others, ‘Maternal and neonatal safety outcomes after SAR-CoV-2 vaccination during pregnancy: a systematic review and meta-analysis’, BMC Pregnancy and Childbirth, 22, no. 581 (21 July 2022), https://doi.org/10.1186/s12884-022-04884-9 D. Zaçe, E. La Gatta, L. Petrella and M.L. Di Pietro, ‘The impact of COVID-19 vaccines on fertility – A systematic review and meta-analysis’, Vaccine, 40, no. 42 (2022), https://doi.org/10.1016/j.vaccine.2022.09.019
Michael P. Rimmer, Jhia J The, Scott C. Mackenzie, and Bassel H Al Wattar, ‘The risk of miscarriage following COVID-19 vaccination: a systematic review and meta-analysis’ Human reproduction, 38, no. 5 (2023), https://pubmed.ncbi.nlm.nih.gov/36794918/
Elisheva D Shanes, Sebastian Otero, Leena B Mithal, Chiedza A Mupanomunda, Emily S Miller, and Jeffery A Goldstein, ‘Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccination in Pregnancy: Measures of Immunity and Placental Histopathology’, Obstetrics and gynaecology, 138, no. 2 (2021), https://doi.org/10.1097/AOG.0000000000004457

¹³⁶⁵ Steven Black, Juhani Eskola, Claire-Anne Siegrist, Neal Halsey, Noni MacDonald, and others, ‘Importance of background rates of disease in assessment of vaccine safety during mass immunisation with pandemic H1N1 influenza vaccines’, The Lancet, 374, no. 9707 (2009), https://doi.org/10.1016/S0140-6736(09)61877-8

¹³⁶⁶ COVID-19 Vaccine Independent Safety Monitoring Board, Final report 2022: COVID-19 Vaccine Independent Safety Monitoring Board (3 July 2023), https://www.tewhatuora.govt.nz/publications/finalreport-of-the-covid-19-vaccine-independent-safety-monitoring-board-cv-ismb, p 21
Smriti Prasad, Erkan Kalafat, Helena Blakeway, Rosemary Townsend, Pat O’Brien, and others, ‘Systematic review and meta-analysis of the effectiveness and perinatal outcomes of COVID-19 vaccination in pregnancy’, Nature Communications, 13, no. 2421 (10 May 2022), https://doi.org/10.1038/s41467-022-30052-w
Abdulrahman Ibrahim Hagrass, Hossam Waleed Almadhoon, Mohammed Al-kafarna, Bashar Khaled Almaghary, Anas Zakarya Nourelden, and others, ‘Maternal and neonatal safety outcomes after SAR-CoV-2 vaccination during pregnancy: a systematic review and meta-analysis’, BMC Pregnancy and Childbirth, 22, no. 581 (21 July 2022), https://doi.org/10.1186/s12884-022-04884-9
D. Zaçe, E. La Gatta, L. Petrella and M.L. Di Pietro, ‘The impact of COVID-19 vaccines on fertility – A systematic review and meta-analysis’, Vaccine, 40, no. 42 (6 October 2022), https://doi.org/10.1016/j.vaccine.2022.09.019
Michael P. Rimmer, Jhia J The, Scott C. Mackenzie, and Bassel H Al Wattar, ‘The risk of miscarriage following COVID-19 vaccination: a systematic review and meta-analysis’, Human reproduction, 38, no. 5 (2 May 2023), https://pubmed.ncbi.nlm.nih.gov/36794918/
Clément Bernard, Tom Duchemin, Lise Marty, Jérôme Drouin, Sara Miranda, and others, ‘First-Trimester mRNA COVID-19 Vaccination and Risk of Major Congenital Anomalies’, JAMA Network Open, 8, no. 10 (15 October 2025), https://doi.org/10.1001/jamanetworkopen.2025.38039

¹³⁶⁷ Medsafe, ‘Release of information relating to the approval process for the meningococcal B vaccine (MeNZB) application’ (revised 13 May 2013), https://www.medsafe.govt.nz/hot/papersreports/menzb/vscminutes05apr2004.htm

¹³⁶⁸ National Vaccine Injury Compensation Program, ‘Vaccine Injury Table’, Health Resources and Services Administration (2017), https://www.hrsa.gov/sites/default/files/hrsa/vaccinecompensation/vaccine-injury-table.pdf

¹³⁶⁹ Medsafe, ‘Alert Communication Myocarditis and pericarditis – rare adverse reactions to Comirnaty (Pfizer COVID-19 vaccine)’ (21 July 2021), https://www.medsafe.govt.nz/safety/Alerts/comirnatymyocarditis-alert.htm

¹³⁷⁰ Laura Semenzato, Stéphane Le Vu, Jérémie Botton, Marion Bertran, Marie-Joelle Jabagi, and others, ‘COVID-19 mRNA Vaccination and 4-Year All-Cause Mortality Among Adults Aged 18 to 59 years in France’, JAMA Netw Open., 8, no. 12 (4 December 2025), https://pubmed.ncbi.nlm.nih.gov/41343214/

¹³⁷¹ Laura Semenzato, Stéphane Le Vu, Jérémie Botton, Marion Bertran, Marie-Joelle Jabagi, and others, ‘COVID-19 mRNA Vaccination and 4-Year All-Cause Mortality Among Adults Aged 18 to 59 years in France’, JAMA Netw Open., 8, no. 12 (4 December 2025), https://pubmed.ncbi.nlm.nih.gov/41343214/ Cecila Acuti Martellucci, Angelo Capadici, Graziella Soldato, Matteo Fiore, Enrico Zauli, and others, ‘COVID-19 vaccination, all-cause mortality, and hospitalization for cancer: 30-month cohort study in an Italian province’, EXCLI J., 24, 690-707 (1 July 2025), https://doi.org/10.17179/excli2025-8400