Has your vaccine worked? Are you immune to Covid-19?

What we know about immunity and Covid-19: assessing your level of immune response to an infection and your vaccine

Dr Quinton Fivelman, PhD. Chief Scientific Officer, London Medical Laboratory, May 2021

Introduction

Several Covid-19 vaccines, having demonstrated that they are both safe and effective, have now been granted emergency use authorisation in most countries. As Covid vaccines have only been developed in the past months, it is too early to know the level and duration of protection of these vaccines to SARS-CoV-2, the virus that causes Covid-19. Research is still ongoing, although it is encouraging that available data suggest that most people who recover from a COVID-19 infection develop an immune response that provides at least some period of protection against reinfection and illness.

An effective Covid-19 vaccine will produce a strong, long-term, adaptive immune response. It might stimulate B cells and specific anti-virus antibodies, or T cells, or a combination of both. Currently, the best marker that we have of protection from future disease is the level of neutralising antibody which is found in the blood. This is an antibody which directly fights the virus and can stop viral entry into cells and thus severe disease progression.

When new vaccines are developed, it is only through ongoing widescale use that we can better understand their ability to prevent transmission, how strong this protection is and the duration of immunity. Because of this, it has been too soon to say exactly how long these COVID-19 vaccines will protect people for, and whether we might need a booster shot further in the future. Although, data does show that vaccine-mediated immunity is preferable and safer than naturally acquired immunity.

Everybody is different and thus everyone responds differently to infections and vaccinations. There are differing degrees of immunity and some people create a very effective immune response which can vary with age. Immunity is also difficult to measure, although the best and easiest marker we currently have is neutralising antibodies, which have been shown to persist in some individuals for many months after original infection.

This paper summarises and answers many of the questions surrounding immunity to SARS-CoV-2 infections and vaccines. Questions covering the length of immunity, how it can be measured and how long it lasts are discussed. There have been increasing references in the press regarding immunity and ‘vaccine passports’ with many governments looking to introduce some form of immunity checks for border entry or events. Understanding longevity and level of immunity conferred by a vaccine will be vital for us to better manage the impact of this pandemic.

What do we know about immunity to natural SARS-CoV-2 infections?

Some people create a very effective immune response from a natural Covid-19 infection, so they will not get sick again from SARS-CoV-2 and will not pass the virus to anyone else – this is called ‘sterilising’ immunity. Other people will develop an immune response along with antibodies and be protected against Covid-19, but they may still be infected with the SARS-CoV-2 virus and transmit it to others – so called ‘protective’ immunity.

People vary in their immune response and quality of immune response to a natural infection. This often depends on various factors such as age, immune status (e.g. if you are immunocompromised) and disease severity. Many reports have shown that people who are sicker with Covid-19 and/or have higher viral loads develop more antibodies and thus might have better protection against future infections.

Studies of immune responses to infection have shown that majority of people have an immune response for several months after an infection, usually 6 to 8 months. A 2020 British study in healthcare workers concluded that the presence of anti-virus IgG antibodies was associated with a substantially reduced risk of SARS-CoV-2 reinfection in the ensuing 6 months (see further reading). Although immunity does appear to be lost over time, SARS-CoV-2 is such a new virus so research is still ongoing how long protection from future disease will last and what level of immunity is protective.

How do the vaccines work?

Covid-19 vaccines teach our immune systems how to recognize and fight the virus that causes Covid-19. The vaccines enter your cells and produce billions of parts of the spike receptor binding domain (RBD) or spike portion which is located on the outside of the virus. This causes the body to develop an immune response and produce neutralising antibodies which recognise the virus and fight it off. These spikes help the viruses attach to cells and cause disease.

Vaccines have been thoroughly tested and provide a controlled dosage of virus exposure compared to a natural infection which can cause significant disease. Vaccination is a much safer way to gain protection than through natural infection.

It typically takes at least two weeks after vaccination for the body to build protection (immunity) against SARS-CoV-2 and some vaccines require more than one dose. That means it is possible a person could still get Covid-19 before or just after vaccination and then get sick because the vaccine did not have enough time to provide protection.

What about immunity to Covid-19 from vaccines?

The currently available Covid-19 vaccines are designed to maximise your body’s immune response to the virus. They focus the virus fighting cells and antibodies to the spike portion of SARS-CoV-2 rather then the whole virus itself which occurs with natural infections. This allows for a far greater immune response which should translate into better protection against future Covid-19 infections.

The current authorised vaccines have been shown to significantly prevent moderate and severe Covid-19 and can reduce the number of people that get sick from the disease. It is not clear whether any of the vaccines stop people becoming infected or whether they can still become infectious and spread the virus. The global vaccination program is only in its infancy and more time needs to pass between the vaccines first being administered in humans to fully understand vaccine-induced immunity.

People respond to vaccines in different ways. Older people and immunocompromised people might not make as good an immune response to the vaccine compared with a young healthy person. Studies have shown that there is a wide variation between individuals’ responses to the vaccine, but this research is still ongoing. Published immunity data from research of the disease suggests that immunity will last for at least a year which may mean that we need to revaccinate higher risk people annually with so called ‘booster shots’ like we do with the flu each year.

How can I measure my immune response to an infection with or a vaccine against SARS-CoV-2?

It is well-known that an infection of the coronavirus SARS-CoV-2 leads to an immune response which can be detected by IgG (immunoglobulin G) antibody tests. IgG anti-virus antibodies are found in all body fluids and are the most common, making up to 80 percent of the antibodies in your body. IgG is known as the long-term antibody which tends to appear one to two weeks post-infection and peaks around a month after initial exposure. While immunity can also be measured by looking at memory immune cells, methods for doing this easily and at scale are not currently available.

The first-generation antibody tests mostly detected the nucleoprotein of the virus, an internal protein of the virus around its nucleus. This was initially chosen to avoid any false positives brought on by infections with other more common coronaviruses which can cause colds. The downside was that unless one had a moderate or severe illness, the antibody test often returned a negative result.

The new generation of IgG antibody tests such as the Abbott Diagnostics SARS-CoV-2 IgG II test which London Medical Laboratory offers assesses the body’s response to the spike protein on the outside of the virus, particularly IgG neutralising antibodies against the spike portion of SARS-CoV-2. The spike protein is the main protein that is associated with the body mounting an immune response to the virus. It is also the protein which all the immunisations are mimicking to get the body's immune system to fight off the virus. Studies have shown that the majority of people have a far higher antibody response to a vaccine against Covid-19 then from a natural infection.

How does an antibody response correlate with immunity?

Antibody tests can help you to know how your immune system has responded to vaccination or an infection to confirm whether the illness you had was Covid-19 or something else. It is not yet clear whether how your immune response relates to whether you are immune or not. Research into this is ongoing so do not presume you are immune, even with a positive result. This virus has not been around for long enough for the scientists to be sure whether or not having IgG antibodies does make you immune – even at high antibody levels.

It would be expected that individuals with high levels are better protected against new infection by current viral strains, although studies are still ongoing. Also, antibody levels against Covid-19 infection are known to decrease with time so high antibody levels may not protect against infection by new variants so it is important to stick to government guidelines on the prevention of spread. Scientists are monitoring emerging virus variants and vaccine companies indicate that they are working on next generation vaccines which will include the new variants.

Can I test positive on a viral test after having a Covid-19 vaccine?

None of the authorised Covid-19 vaccines cause you to test positive on viral tests such as a RT-PCR or rapid antigen test, which are used to see if you have a current infection and often used for travel. None of the authorised vaccines currently available contain the live virus that causes Covid-19. If your body develops an immune response to vaccination, which is the goal, you should test positive on some antibody tests. Antibody tests can also indicate you had a previous SARS-CoV-2 infection and that you may have some level of protection against the virus.

What about these Covid-19 ‘immunity passports’ I hear about?

There are increasing numbers of reports and government statements regarding immunity and proposed ‘vaccine passports’. Some countries are talking about introducing some form of immunity checks for border entry or large events. Vaccine passports already exist for certain diseases such as Yellow Fever and these are checked at many borders.

However, because of the wide immune response variation to a Covid-19 infection or vaccination coupled with indications that immunity may decrease over time, governments could only issue ‘immunity passports’ if there were clear and accurate ways of measuring a person’s immunity to infection and knowing how long it will last. Antibody tests are a valuable tool to investigate such immunity and further research will provide a better understanding of how our bodies react to Covid-19 infections and vaccinations.

Further reading:

• London Medical Laboratory's Coronavirus Vaccine & Immune Response - "Quantitative" Antibody Home Blood Test
• UK Coronavirus Immunology Consortium - https://www.uk-cic.org/
• British Society for Immunology - https://www.immunology.org/coronavirus

Lumley S.F., et al. Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers. N Engl J Med 2021; 384:533-540 (https://www.nejm.org/doi/full/10.1056/NEJMoa2034545)