About the Comirnaty™ vaccine (from Pfizer/BioNTech)

Comirnaty™ is a vaccine that protects against COVID-19 disease caused by the SARS-CoV-2 virus.

How the vaccine works

The Comirnaty™ COVID-19 vaccine is a messenger RNA (mRNA) vaccine. It contains a small strip of genetic material encased within a lipid (fat) bubble. It does not contain any live virus.

The SARS-CoV-2 virus that causes COVID-19 has characteristic crown-like protein spikes on the surface that it uses to infect your airways. The mRNA COVID vaccine, Comirnaty®, provides your body with the instructions to make copies of the SARS-CoV-2 spike protein so that your immune system can learn to recognise it. If you are later exposed to the real virus, your body can act quickly to block the virus entering your cells and to protect you from illness. 

Although mRNA is a type of genetic material, it is not a piece of our genome. Messenger RNA does not enter the nucleus of the cell and cannot interact with our own genetic code. As soon as the spike protein has been made, the mRNA is breaks down rapidly and is recycled.

More information on mRNA vaccines:

Comirnaty™ vaccine effectiveness

The safety and effectiveness data for Comirnaty both from the clinical trials and now from extensive use, after many millions of doses, are excellent. We can be confident it has a reassuring safety profile and it is highly effective against symptomatic disease and severe COVID-19. Early data suggests that the vaccine can reduce asymptomatic infection and therefore reduce spread. 

Vaccine safety

The safety profile of Comirnaty™ is like that of other vaccines given in New Zealand. Some people experience mild to moderate discomfort at the injection-site and flu-like symptoms (such as headache, muscle and joint aches, fever) for just a day or two after vaccination. These are more commonly reported after the second dose and in younger adults. This is an expected response not experienced by everyone. 

As a precaution, it is strongly advised to wait 20 minutes after vaccination in case of very rare (4–5 cases per million doses), but serious, allergic reactions. You may be asked to wait longer if you have a history of severe immediate allergic reactions to any other products.

How Comirnaty is manufactured

RNA vaccines can be produced very rapidly. The manufacturing process does not require any cells or live virus, as it is based purely on chemical building blocks that can be scaled up to produce large quantities of identical RNA in specialised manufacturing facilities. A DNA template, created chemically from an electronic copy of the virus genetic sequence, is used to produce the RNA that has the instructions for only the virus spike protein. 

This way of making vaccines means that alterations can be made rapidly if the virus changes so much that vaccine becomes less effective. For more details on this process of making RNA see this article

How the vaccine works

The Comirnaty™ COVID-19 vaccine is a messenger RNA (mRNA) vaccine. It contains a small strip of genetic material protected inside a lipid (fat) bubble. It does not contain any live virus.

The SARS-CoV-2 virus that causes COVID-19 has characteristic crown-like protein spikes on the surface. The virus uses this spike to infect our cells, particularly those in our airways. The mRNA COVID vaccine, Comirnaty®, provides your body with the instructions to make only this SARS-CoV-2 spike protein. 

Following injection with an mRNA vaccine, the mRNA in a protective lipid bubble is taken up by cells local to the injection site. Once inside the cell, the mRNA works with our own cells’ machinery to produce the spike protein. The newly formed spike protein is presented to the immune system to induce a strong immune response, allowing our bodies to learn to recognise the virus and create a new immunological memory. Then, if the body is exposed to the real virus, it can act quickly to stop illness or, at least, reduce the severity of the illness. 

Although mRNA is a piece of genetic material, it is not a piece of our genome. Messenger RNA does not enter the nucleus of the cell and cannot interact with our own genetic material. As soon as the spike protein has been made, the mRNA breaks down rapidly and is recycled.

More information on mRNA vaccines:

How Comirnaty is manufactured

RNA RNA vaccines can be produced very rapidly. To make the RNA for this vaccine, a DNA template with the code to make the SARS-CoV-2 virus spike protein is first made in a laboratory using an electronic version of the virus’s genetic sequence. This process does not require any cells or live virus, it is based purely on chemical building blocks that can be scaled up to produce large quantities of identical RNA in specialised manufacturing facilities. As happens naturally in our cells to make our own proteins, through a process called transcription the DNA template is used to make messenger RNA carrying a copy of the instructions for a specific protein – in this case, the virus spike protein. The mRNA can then be extracted and encapsulated in a protective bubble (lipid nanoparticle) ready for use in the vaccine. For more details on this process see this.

 

RNAOne of the reasons why this vaccine was able to be produced faster than other vaccine candidates was because the genetic sequence for the SARS-CoV-2 virus was made available to the world as soon as the new virus was identified and the technology to use it was already being used to investigate other vaccine candidates (including influenza and tuberculosis).

This rapid ability to produce new vaccine, based on an electronic sequence sent by computer, means that if the current vaccine loses effectiveness against new virus variants, the production of this vaccine can be quickly altered to match the new variant with minimal changes needed to the production process.

Comirnaty™ vaccine effectiveness

The safety and effectiveness data for Comirnaty both from the clinical trials and now from extensive use, after many millions of doses, are excellent. We can be confident it has a reassuring safety profile and it is highly effective against symptomatic disease and severe COVID-19. Early data suggests that the vaccine can reduce asymptomatic infection and therefore reduce spread. 

Preliminary data from pivotal phase III clinical trial from age 16 years (included just under 44,000 vaccinated and unvaccinated placebo controls) and from Israeli vaccination programme (included around 1.2 million vaccinated and unvaccinated individuals aged from 16 years) that this is a highly effective vaccine, as shown here:

Two-doses of mRNA-COVID vaccine (Comirnaty™) given 21 days apart. Clinical trial vaccine efficacy compared with placebo control Real-life vaccine effectiveness compared with unvaccinated individuals
  VE% 95% CI VE% 95% CI
Documented SARS-CoV-2 infection - - 92 88-95
Symptomatic COVID-19 95 90 - 98 94 87-98
Hospitalised with COVID-19 - - 87 55-100
Severe COVID-19 disease 95 90-98 92 75-100
Death associated with COVID-19 - - 92 88-95

Early data from the US also shows that the mRNA COVID-19 vaccines are effective at preventing SARS-CoV-2 infection in frontline staff and health care workers in real-world conditions. Vaccine effectiveness against infection was 80% (95% CI 59-90) from 14 days after the first dose and 90% (68-97) from 14 days after the second dose.

Vaccine safety

The safety profile of Comirnaty™ is like that of other vaccines given in New Zealand. Some people can experience mild to moderate discomfort at the injection-site and flu-like symptoms for just a day or two after vaccination. These are more commonly reported after the second dose and in younger adults. This is an expected response not experienced by everyone. 

As this vaccine does not contain live virus, it is suitable for use in those with compromised immune systems and older adults. Safety is being closely monitored globally.

Vaccine should not be given to:

  • Anyone with severe allergy (anaphylaxis) to a previous dose of this vaccine or a component of the vaccine.
  • Administration of Comirnaty™ should be postponed in individuals suffering and acute severe febrile illness (fever over 38°C) or who are systemically unwell. The presence of a minor infection is not a reason to delay immunisation.

It is strongly advised to wait 20 minutes after vaccination in case of very rare, but serious, allergic reactions. A definite history of any immediate allergic reaction to any other product is a precaution but not a contraindication to vaccination with Comirnaty™. In this case, a 30-minute wait is advised for observation to be able to administer prompt treatment, if required. 

Comirnaty (COVID-19)
Common response Pain at injection site
Headache
Fatigue
Muscle aches
Chills
Fever
Joint aches
Nausea
Rare responses Lymphadenopathy (swollen lymph nodes)
As with any medicine, very rarely a severe allergic reaction (anaphylaxis) can occur following immunisation.

Adverse events seen during clinical trial

A combined phase I/II/III clinical trial was pivotal for the vaccine’s regulatory approval by Medsafe. Reported adverse events at the time of cut-off for the preliminary safety analysis, which included over 18,800 vaccinated adults and 18,800 placebo controls, were related to transient reactogenicity (reaction to the vaccine). Sixty-four vaccine recipients and six in the placebo groups experienced swelling of the local lymph nodes (lymphadenopathy). Four potentially vaccination-related serious adverse events were reported in the vaccine groups – shoulder injury related to vaccine administration, lymphadenopathy, heart arrhythmia (paroxysmal ventricular arrhythmia) and right leg paraesthesia (abnormal sensation). Two deaths during the clinical trial were not considered related to the vaccine, placebo or due to COVID-19.

Adverse events will continue to be monitored as part of the clinical trial follow-up for at least 2 years. As part of the early follow-up, acute peripheral facial paralysis (or Bell’s palsy) was reported by four participants in the vaccinated group. This has not been causally linked to the vaccine and no safety signal has been shown so far by real-world safety monitoring.

Real-world safety monitoring

As well as through clinical trials, safety data is being continually collected by drug and vaccine safety surveillance systems, globally, either through passive reporting or enhanced surveillance using smartphone apps through which, those who have been vaccinated to record their experiences post vaccination.

Furthermore, as part of Coalition for Epidemic Preparedness Innovation (CEPI)-funded Safety Platform for Emergency vaccines (SPEAC), templates have been created for vaccine developers to consider adverse events of special interest (AESI) in their study designs. A list of AESI has been developed specifically for COVID-19 vaccines, based on proven or theoretical potential concerns related to how the vaccine works or to SARS-CoV-2 viral infection.

Data presented to the CDC in early March 2021 reported that no AESI concerns have been signalled for Comirnaty™ through weekly monitoring.

Comirnaty vaccine FAQs

COVID-19 vaccines in pregnancy and breastfeeding

Pregnancy is a precaution for vaccination with the mRNA COVID vaccine, Comirnaty™ because initial clinical studies have not investigated the mRNA vaccine given in pregnancy – a phase 2/3 clinical trial is now underway in the US including pregnant women. A study in the US in which around 35,000 women have received mRNA COVID-19 vaccines in pregnancy found no safety concerns for pregnancy or birth outcomes. Based on how the vaccine works, there are no safety concerns about receiving this vaccine in pregnancy, whereas COVID-19 can be very severe for pregnant women and can lead to premature births or miscarriage.

We recommend that people who are pregnant and at risk of being exposed to SARS-CoV-2 virus receive COVID-19 vaccination at any stage of pregnancy. When the risk of exposure to the virus is low, it is possible to delay vaccination until after the baby is born. We prefer to only give vaccines and medicines during pregnancy when they are necessary to protect or maintain the health of the mother and/or her baby.

As with all vaccines on the New Zealand Immunisation Schedule, there are no safety concerns about giving mRNA COVID-19 vaccine to women who are breastfeeding and by being vaccinated, mothers can provide some protection against COVID-19 for their babies in breastmilk.

More information:

Reference

Shimabukuro TT, Kim SY, Myers TR, et al. Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons. N Engl J Med. 2021 DOI: 10.1056/NEJMoa2104983

Is the Comirnaty vaccine safe and effective for people living with HIV?

The vaccine has been through rigorous testing to ensure safety and efficacy and is now being used widely overseas without any serious concerns appearing. People with HIV were included in clinical trials though efficacy and safety data specific to this group are not yet available.

With some vaccines people living with HIV can produce a weaker response. Those with a supressed viral load and CD4 cells> 350 cells/ ml can reasonably expect to have an appropriate response to the vaccine based on what we know about the responses of people living with HIV to other vaccines. Those who are not on treatment would be sensible to start treatment and have the vaccine once their viral load is suppressed. 

HIV medications do not alter the effectiveness of the COVID-19 vaccines and the vaccines do not affect how well HIV medications work either. 
 

What is the guidance around receiving a COVID-19 vaccine and having a general anaesthetic?

Based on first principles and our experience with other vaccines, there is no expectation that an anaesthetic would affect the safety or immunogenicity of the mRNA COVID-19 vaccine.

The general recommendation when planning vaccination with any vaccine is explained in Section 3.1.3 in the Immunisation Handbook 2020

What is the acceptable timeframe between the first and second doses of the Comirnaty vaccine?

To be fully immunised with Comirnaty requires two doses given at least 21 days apart.

Vaccinators are advised not to give the second dose earlier than this, and while longer spacing is acceptable, the recommended spacing is for the second dose to be given as close after 21 days as possible.

Can other vaccines be administered with a COVID-19 vaccine?

Currently Medsafe advice is only available for the mRNA vaccine from Pfizer/BioNTech (Comirnaty™) vaccine.

A two-week gap is generally recommended after any non-live vaccine, including influenza, and the Comirnaty mRNA COVID-19 vaccine. If a live vaccine, such as MMR, varicella and zoster vaccine has been given, then a four-week gap is generally recommended before Comirnaty. If Comirnaty, is given first, then maintain a two week gap before any other vaccines. Do not delay if a gap between these vaccines is not practicable.

Please note that two doses of the mRNA vaccine are required, given at least 21-days apart. These recommendations are continually being reviewed.

What is the priority - an influenza vaccine or a COVID-19 vaccine?

The COVID-19 mRNA vaccine two-dose schedule should take priority over influenza (flu) vaccine.

The flu vaccine can be administered two weeks after the second dose of COVID-19 vaccine, which is given at least 21 days after the first dose. 

If a person is vaccinated against COVID-19, will they still be able to spread the virus to susceptible people?

An ideal vaccine stops everyone from carrying and passing on the infection as well as protecting them from becoming seriously ill. It is currently unclear whether COVID-19 vaccines only protect against symptomatic and severe disease, or if they can also stop all infection, including asymptomatic infection (i.e. showing no symptoms).

If the vaccine is only able to stop the symptoms of the disease, but unable to stop the virus from infecting us and reproducing, then the virus may still be able to be spread. Even in this case, by reducing the number of people with symptoms will help to reduce spread of the virus because fewer people will be coughing large quantities of virus on others. However, this possible limitation of the vaccine highlights the importance of continuing to follow public health advice such as hand washing and isolating if unwell, even post vaccination. For more information, please click here.

Recently published data from Israel showed that its mass COVID-19 vaccination campaign (using the Pfizer vaccine) was working well with two doses cutting symptomatic cases by 94% across all age groups. Data reported by the CDC in the US has also shown that mRNA COVID-19 vaccines were 90% effective in health care workers against SARS-CoV-2 infection (with and without symptoms).

How long will COVID-19 vaccine immunity (i.e. protection from the COVID-19 disease) last?

We would expect COVID-19 vaccines to provide protection for longer than 2 months, although exactly how long for, remains unknown at this stage. This is because not enough time has passed since the clinical trials started to be able to accurately answer this.

We know that the Pfizer/BioNTech COVID-19 vaccine lasts for AT LEAST two months, because data supporting this has been reviewed by Medsafe. As part of the conditional approval of the Pfizer/BioNTech COVID-19 vaccine, more data is to be provided as it becomes available. It is anticipated that further data will be provided on durability of the immune response post vaccination in coming months.

How many doses of COVID-19 vaccine should I have? I already received a COVID-19 vaccination overseas.

If you were partially vaccinated overseas with one dose of Comirnaty (Pfizer/BioNTech) vaccine, you will need to have another dose at least 21 days after your previous dose. There is no maximum time limit between doses, so you do not need to repeat the first dose or receive a third dose.

If you received one dose of different vaccine (for example, COVID-19 vaccine AstraZenaca/Vaxzevria/Covishield or the Moderna mRNA COVID-19 vaccine), the current recommendation is to have one dose of the Comirnaty vaccine when it becomes available for your priority group at least 4 weeks after your first vaccine. These vaccines are not interchangeable, but you are likely to have a good response to just one dose. If you received one dose of the Janssen/Johnson & Johnson vaccine, you are considered fully immunised and do not require any further doses of COVID-19 vaccine.

Can I delay receiving my second dose of Comirnaty?

It is recommended to have the second dose of Comirnaty™ at least 21 days after the first dose. A delay for longer than 21 days is not considered to be a problem in terms of how you will respond to the second dose.

It is not yet known, for how long the first dose provides protection. If you are at risk of exposure to SARS-CoV-2, it is advisable to have the second dose when recommended. During clinical trials, the vaccine efficacy against symptomatic COVID-19 between the first and second doses was around 50% compared with 90% within 2 days of the second dose increasing to 95% after a week. Recent real-world data has shown that protected against SARS-CoV-2 infection was around 62 to 91% from 14 days after dose one and 68 to 97 % from 14 days after dose two in frontline workers. 

References

  • Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020;383(27):2603-15.
  • Thompson M, Burgess J, Naleway A, et al. Interim Estimates of Vaccine Effectiveness of BNT162b2 and mRNA-1273 COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Health Care Personnel, First Responders, and Other Essential and Frontline Workers — Eight U.S. Locations, December 2020–March 2021. MMWR Morb Mortal Wkly Rep, 2021.
  • Dagan N, Barda N, Kepten E, Miron O, Perchik S, Katz MA, et al. BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting. New England Journal of Medicine. 2021.
  • Clancy, S. & Brown, W. (2008) Translation: DNA to mRNA to Protein. Nature Education 1(1):101
  • Comirnaty data sheet https://www.medsafe.govt.nz/profs/Datasheet/c/comirnatyinj.pdf
  • Petousis-Harris H. Assessing the Safety of COVID-19 Vaccines: A Primer. Drug Saf. 2020;43(12):1205-10.
  • Law B, Sturkenboom M. D2. 3 Priority list of adverse events of special interest: COVID-19. The Brighton Collaboration. https://brightoncollaboration.us/wp-content/uploads/2020/06/SPEAC_D2.3_V2.0_COVID-19_20200525_public.pdf.
  • Shimbabukuro T, CDC-COVID-19 Vaccine Task Force. COVID-19 vaccine safety update. March 2021. 2021 1 March 2021.Available from: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-02/28-03-01/05-covid-Shimabukuro.pdf