How do COVID-19 vaccines work?

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COVID-19 vaccines work by introducing the immune system to an inactivated form of the SARS-CoV-2 coronavirus or a part of it. This does not cause COVID-19 but equips the body to fight against future infection with the virus.

All data and statistics are based on publicly available data at the time of publication. Some information may be out of date. 

All vaccines work by training the immune system to respond to future infection. Vaccines are overwhelmingly safe for the majority of people who receive them, and they do not cause disease.

There are 12 vaccines against COVID-19 that have authorization for use in various locations around the world.

Vaccine developers worked under unprecedented conditions to develop vaccines against COVID-19 after the emergence of the SARS-CoV-2 virus in late 2019. It took less than a year for the first COVID-19 vaccines to gain authorization for use.

While this is significantly faster than for all other vaccines, developers leveraged existing vaccine technology and a concerted global effort — working alongside health authorities such as the Food and Drug Administration (FDA) — to work at this pace.

In this Special Feature, we take a look at how different COVID-19 vaccines work and what scientists mean when they talk about side effects and vaccine efficacy.

Specifically, we cover:

  • mRNA vaccines
  • viral vector vaccines
  • subunit vaccines
  • inactivated vaccines
  • vaccine side effects
  • vaccine efficacy
Different vaccine types

Although all of the COVID-19 vaccines in use around the world aim to achieve the same goal — namely, protection from COVID-19 — they employ different vaccine technologies.

Some vaccines are based on the whole SARS-CoV-2 virus, others use only parts of it, and some do not use any material derived directly from the virus.

The sections below provide an overview of the different types of COVID-19 vaccines that have authorization for use in at least one country.

mRNA vaccines

The COVID-19 mRNA vaccines that BioNTech-Pfizer and Moderna developed are the first mRNA vaccines authorized for use in humans outside of clinical trials. However, the technology is not new.

Scientists have been working on mRNA vaccine candidates for infectious diseases and cancer for a number of years.

mRNA vaccines do not contain any part of the SARS-CoV-2 virus. Instead, they carry a chemically synthesized piece of messenger (m)RNA that contains the information necessary for our own cells to make the SARS-CoV-2 spike protein.

Our cells make this protein and present it to our immune system, which responds by creating antibodies and developing longer lasting immunity in the form of T cell and B cell responses.

It is not possible to develop COVID-19 from an mRNA vaccine because it does not carry the instructions necessary to make the entire coronavirus.

Read more about mRNA vaccines here.

Viral vector vaccines

Like mRNA vaccines, viral vector vaccines also do not contain the whole SARS-CoV-2 virus. They use a harmless virus to deliver the gene that allows our cells to make the spike protein.

The Oxford-AstraZeneca, Sputnik V, and Johnson & Johnson COVID-19 vaccines are all viral vector vaccines that use different adenoviruses as the delivery system, or vector. Adenoviruses can cause the common cold, and there are many different types of adenoviruses that can infect different species.

The Oxford-AstraZeneca vaccine uses a chimpanzee adenovirus vector called ChAdOx1. The Russian Sputnik V vaccine uses two different human adenovirus vectors called Ad26 and Ad5. Johnson & Johnson also use the Ad26 virus in their vaccine.

All three vaccines contain the gene for the spike protein and deliver this into cells after injection. The cells then make the spike protein and present it to our immune system.

As with mRNA vaccines, viral vector vaccines do not carry the information necessary for our cells to make the entire SARS-CoV-2 virus. Therefore, they cannot cause COVID-19.

Read more about viral vector COVID-19 vaccines here.

Subunit vaccines

Like mRNA and viral vector vaccines, subunit vaccines only use a part of the SARS-CoV-2 virus. However, rather than providing our cells with the genetic code necessary to make a viral protein, subunit vaccines deliver the protein directly.

The Novavax COVID-19 vaccine candidate is a subunit vaccine. Scientists produced large amounts of the SARS-CoV-2 spike protein in a laboratory for this experimental vaccine. Novavax use insect cells to grow the proteins before purifying them. The purified proteins then form nanoparticles.

On their own, the protein nanoparticles may not produce a strong enough immune reaction, so Novavax add an adjuvant. This is a chemical that stimulates the immune system.

Subunit vaccines do not carry enough viral material to make the whole SARS-CoV-2 virus. Therefore, they cannot cause COVID-19.

Read more about subunit vaccines here.

Inactivated vaccines

Unlike mRNA, viral vector, and subunit vaccines, inactivated vaccines contain the entire SARS-CoV-2 virus. However, the virus is chemically modified to inactivate it, which means that it cannot cause disease.

Sinovac, Sinopharm, and Bharat Biotech all use a chemical called beta-propiolactone to inactivate the SARS-CoV-2 virus in their vaccines. The chemical modifies the virus’s genetic material.

Inactivated COVID-19 vaccines cannot cause COVID-19, as the virus cannot make copies of itself.

This type of vaccine does not produce as strong an immune reaction as some others, and the resulting immunity may not be as long lasting. Sinovac, Sinopharm, and Bharat Biotech use adjuvants in their COVID-19 vaccines to generate a stronger immune response.

To provide immunity in the long run, it may be necessary to receive booster shots after receiving an inactivated COVID-19 vaccine.

Read more about inactivated COVID-19 vaccines here.

Side effects and efficacy

All experimental vaccines undergo rigorous testing in preclinical studies and clinical trials. These are designed to assess the safety of the vaccine and how well it fares at preventing disease.

Scientists measure the safety of a vaccine candidate by monitoring side effects in the trial participants.

By looking at how many people develop side effects in the group who had an experimental vaccine and comparing this with the side effects in the group who had the placebo, they can determine how safe a vaccine candidate is.

This also allows them to gather data on the likelihood that people receiving the vaccine will experience side effects.

For example, 84.7%Trusted Source of people who received the Pfizer-BioNTech COVID-19 vaccine during clinical trials reported at least one side effect at the injection site.

The most common side effect was pain, which 83.1% of participants aged 18–55 years and 71.1% of those aged 55 years and above reported.

In a clinical trial, scientists also work out how well an experimental vaccine works. They do this by comparing how many people in the treatment group develop the disease with how many people in the placebo group develop the disease.

This is called vaccine efficacy, and it describes the percentage reduction in disease in the clinical trial.

Researchers have reported an efficacy of 94.1% for the Moderna COVID-19 vaccine.

However, vaccine efficacy is different from vaccine effectiveness. Vaccine effectiveness refers to how well a vaccine works in real life settings (outside of clinical trials). Scientists will continue to study how effective COVID-19 vaccines are in community settings, but it will take some time before robust data are available.

Early reports from Israel show that the rate of new COVID-19 cases among healthcare workers who received the Pfizer-BioNTech vaccine was 85%Trusted Source lower at 15–28 days after the first injection.

This gives us an early indication of how well the vaccine works in the real world.

Read more about vaccine efficacy here.