How does the COVID-19 vaccine work?

How mRNA vaccines, like Comirnaty, work

After injection, the mRNA contained within its lipid bubble is taken up by specialist immune cells (dendritic cells) in the muscle near the injection site. Using our cells’ own protein-making machinery, the mRNA provides the recipe to make a new protein that is known to trigger a good immune response. As normally occurs in our cells, after the protein has been made the RNA is broken down and its components are recycled – its job is done.

Next, the protein produced is carried by the cell to the local lymph node. The protein is shown to lymphocytes (T and B cells) in the lymph node to stimulate a targeted immune response. In this way, the body learns to recognise this virus component to provide future protection against the wild-type virus.

In the case of COVID-19 vaccine, the protein made is a duplicate of the spike protein that is found on the surface of the SARS-CoV-2 virus (the virus that causes COVID-19). On the virus, this protein enables the virus to infect the cells in our airways. The vaccine targets our immune response against this spike protein to block the virus from entering our cells and to stop infection. As a second line of defence, this primed immune response can also quickly kill any cells infected with the virus if it is unable to completely block initial infection. Watch this video for more information. 

Two doses of the vaccine provide highly effective and lasting immunity against the virus.

How protective is this vaccine?

Protection against COVID-19

Vaccine efficacy is the measure of how well a vaccine protects in a clinical trial setting with a controlled population and compared with a control groups – either another vaccine or a saline placebo. Participants are recruited based on a predefined criteria and monitored for certain outcomes known as ‘primary endpoints’. 
The Comirnaty clinical trial primary efficacy endpoint was the occurrence of symptomatic COVID-19 at least 7 days after the second dose. After a known surveillance time (2,200 person years in each group), the study observed 162 cases of COVID-19 in the placebo group compared with 8 cases in the vaccinated group – this gave a vaccine efficacy of 95%. In other words, 95 out of 100 people vaccinated are protected against symptomatic COVID-19. 

Vaccine effectiveness is measured in real-world situations, with a broader population. One way to measure it is to compare vaccinated with unvaccinated people to see if they catch COVID-19. In Israel, they reviewed surveillance data from over 6 million fully vaccinated people and found the vaccine was as effective in real life as in clinical trials; 7 days following two doses of Comirnaty, vaccine effectiveness against SARS-COV-2 infection was found to be 95% against symptomatic COVID-19 and 97% each against hospitalisation and COVID-19-related death. Recent preprint data from the UK continues to show that after two doses Comirnaty is highly effective against symptomatic COVID-19 (80-95%), over 90% against hospitalisation and death.

Protection against spreading the virus

Protection after vaccination can last longer by slowing the spread of the virus. This will work in two ways – to reduce the amount of virus in the community to lower your chance of being exposed to an infected person, and to lower the risk of more infectious and virulent strains emerging that may bypass any immunity generated by the vaccine.

An ideal vaccine stops everyone from carrying and passing on the infection as well as protecting them from becoming seriously ill. Initially, data from Israel showed that its mass COVID-19 vaccination campaign (using the Comirnaty vaccine) was working well with two doses cutting documented infection by 92% across all vaccine-eligible 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). These data showed that Comirnaty can prevent infection as well as symptomatic disease. However, its ability to do this has been reduced with the more infectious variants, such as Delta variant, but data from the UK shows Comirnaty remains around 80% effective against infection.

When 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 to those who are not immunised or have a suboptimal response. Even in this case, if infected, the time you are infectious and producing virus is much shorter which helps to slow the spread. By reducing the number of people with symptoms will help to control the spread of the virus because fewer people will be producing large quantities of virus and spreading it by coughing. A Swedish study showed that the risk of infection to non-immune family members decreased with each family member who was immunised and vaccination was key to reducing the risk of transmission within households. See this Conversation article for further information on infection in vaccinated individuals.

However, particularly with the emergence of more transmissible virus variants, this potential limitation highlights the importance of continuing to follow public health advice such as mask wearing, contact tracing, hand washing and isolating when unwell, even post vaccination. Find more information here.

How long does protection last?

It remains uncertain how long Comirnaty will protect against COVID-19. As part of the conditional approval of the COVID-19 vaccine, further data will be provided on durability of the immune response post vaccination in coming months. The original clinical trial data confirmed protection for at least two months and more recent data released by Pfizer in April 2021 showed protection for at least 6 months. This is similar to those who have had COVID-19, in New Zealand antibodies have been shown to last for at least 8 months without any further boosting.

After vaccination, immune memory of the spike protein in the lymph nodes that can produce high quality and durable antibody responses against SARS-CoV-2 spike protein has been reported. 

The duration of protection against COVID-19, both after vaccination and after the SARS-CoV-2 infection, is dependent on a combination of the following factors and will vary between individuals, countries and changes in the virus.

Factor influencing immunity

Positives and negatives

SARS-CoV-2 virus and COVID-19

  • Variants of concern


The vaccine could become less effective as mutations occurring the virus evolves change the shape of the target antigen

The mRNA and viral vector vaccines are able to be quickly altered as needed;  booster doses would be required

  • Previous infection with COVID-19


A stronger and longer lasting immune response is expected in those who have previously had COVID-19

Vaccination after prior infection can act like a booster dose.

Exposure to the virus after vaccination can also act like a booster dose.

  • Protection against severe disease


Even if immunity wanes with time, it is likely to be sufficient to protect against severe disease

Waning protection may result in mild breakthrough infections in vaccinated people or mild symptoms may last longer.

Vaccine type


It is not yet known how long lived the immunity from this type of vaccine can last

The vaccine may produce a longer lasting or better targeted immune response than the actual disease.

Neutralising antibody decline and boosting

Booster doses may be needed


1. To adjust vaccine to better match circulating strains

2. To increase the levels of antibody

Better fitting antibodies may be required to neutralise the virus

Allowing the disease to circulating may provide a boosting effect in those vaccinated.

No defined correlate of protection

It is not yet known what level of neutralising antibody provides the best protection

The presence of memory T cells and B cells can also provide an added layer of protection

Evidence of long-lived memory B cells after vaccination


These cells remain in the lymph nodes ready to make antibody when activated



Older people often respond less well to vaccines than younger people.

When the antibody levels start at a lower level, protection is lost sooner as levels wane and are too low to prevent disease.

Comirnaty has been shown to be safe and effective in older age groups, particularly against severe disease

Underlying health conditions

Underlying conditions can affect the immune system

These types of conditions increase the risk of severe COVID-19.

Even a reduced immune response provides protection against severe outcomes of COVID-19 and hospitalisation.

Will the vaccine make a person test positive on COVID-19 tests?

No. The nasal swab detects the virus genetic material not proteins, such as antibodies or spike protein. You must be infected by the virus for the genetic material to be detectable in your nose.

Also, the spike protein that is made in using the vaccine’s instructions does not travel far and will not reach your nose because your immune system sees it as foreign and quickly removes it. Likewise, the RNA in the vaccine is also destroyed very quickly if it gets outside of your arm muscle and will not be detectable in your nose.

See references on Comirnaty vaccine overview page

Last updated: 27 October 2021