While the world holds its breath: vaccines are most effective if people have had COVID-19

Disease and treatment 31. may 2022 3 min Clinical Professor Peter Garred Written by Morten Busch

The world is slowly beginning to breathe more easily in the hope that the COVID-19 pandemic may soon be over. Meanwhile, researchers are working hard to understand and predict the immunity that could save us from future waves of COVID-19. A new study answers a key question: why vaccinated people became infected with the Delta variant and, even more often, the Omicron variant. The study also indicates the point at which waning immunity will determine when future waves can strike again.

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Although all statistics show that the COVID-19 vaccines helped to contain the pandemic and reopen the world, some people have doubts. “Were the vaccines even that effective? People got infected anyway, and the Omicron variant might not be so dangerous after all, so maybe it is better just to get infected and get over it.” New research indicates how effective the vaccines have been and how necessary they will be in the future.

“There is no doubt that the COVID-19 vaccines were crucial in controlling the pandemic and protecting against severe illness. However, we have found that the vaccines were not as effective at raising an immune response at mucous membranes, where the body first meets the virus. Conversely, we found that natural infection with SARS-CoV-2 induced immune response at these membranes. The need to vaccinate again in autumn 2022 depends on which new variants appear. Nevertheless, our figures suggest that people’s antibody levels will have declined so much that at least vulnerable groups should be given a booster jab,” explains Peter Garred, Senior Consultant and Professor at the Laboratory of Molecular Medicine, Department of Clinical Immunology at Rigshospitalet and University of Copenhagen.

Investigated declining immunity

The study had 1,754 participants and investigated the factors determining declining immunity among those vaccinated against COVID-19 – most with the Pfizer-BioNTech vaccine and a few with one AstraZeneca jab and one Pfizer-BioNTech jab. The researchers collected blood samples from each participant before vaccination and up to 230 days after the first vaccine dose – 3 to 5 samples per participant – to determine how the level of antibodies varied over time and according to age and sex – and especially in relation to whether a person had COVID-19 before or not.

“People differed in how long the antibodies last. They last a little longer among women than among men and among younger people than among slightly older people. The most crucial finding was that the immunity of naturally infected and vaccinated people lasts longer than among people who had only been vaccinated,” says Peter Garred, who adds that, based on the data, it was possible to project the speed at which antibodies in the blood against SARS-CoV-2 will disappear even beyond the actual observation time.

This finding was closely linked to another finding, namely which types of antibodies the participants had in their blood by distinguishing between immunoglobulin M, A and G. IgM comprises the immune system’s immediate response to external enemies. IgG can recognise enemies that have already entered the body. However, IgA, the antibodies found predominantly on the body’s surfaces and mucous membranes, especially aroused interest.

“We only found a short-term and relatively weak IgA response. Among those vaccinated, it was almost negligible. The response was a little better among those who had had COVID-19, but it still disappeared relatively quickly again. This may explain exactly what we have seen with the recent Delta and Omicron waves: people get infected because the immune response raised by the current vaccines given systematically against SARS-CoV-2 might not be sufficient to avoid transmission at our mucous membranes in the nose and airways. Nevertheless, we are still protected from severe illness due to the IgG antibodies that can neutralise the virus, " explains Peter Garred.

Sterilising immunity

The new study of the long-term effect of COVID-19 vaccines and infection on immunity now provides models for studying and assessing the need for immune response for up to 1 year after vaccination, and this can be significant knowledge when summer and hot weather gives way to winter and a host of infectious diseases. However, whether people need to be vaccinated and specifically which group is still unclear.

“The trials show that immunity declines considerably in 6 months, regardless of whether people are vaccinated or infected. Therefore, my immediate assessment would be that vaccinating the most vulnerable people at the greatest risk of becoming severely ill from COVID-19 would be a good idea. The challenge is that we do not yet know which virus variants will emerge in the autumn, or whether they will be in the form of a very serious variant such as Delta or a slightly milder type such as Omicron, which can still be severe for people with compromised immunity,” says Peter Garred.

The emergence of the Delta and Omicron variants showed that vaccines may effectively protect against severe illness but less effectively prevent infection. Unfortunately, the researchers do not yet know the answer to a key question: exactly which and how many antibodies people must have to protect against infection and severe illness and death.

“In some places, such as hospitals with very sick patients or nursing homes with vulnerable residents, developing high and comprehensive sterilising immunity can be important, to completely prevent transmission. However, this requires neutralising antibodies at the site of infection, such as IgA antibodies in mucosal secretions, so we hope it will be possible to develop, for example, nasal spray vaccines. The idea might sound novel, but needle-free local vaccines have been around for decades."

The first to have a major impact was the oral polio vaccine that was combined with a parenteral vaccine. The oral polio vaccine works by using a weakened virus infecting the gastrointestinal tract and provoking an immune response in the host. 

"There are also oral vaccines for typhoid fever, cholera and rotavirus as well as a nasal vaccine for influenza. The ultimate control of SARS-CoV-2 and COVID-19 will likely require both locally applied and parenteral vaccines,” concludes Peter Garred.

Modeling of waning immunity after SARS-CoV-2 vaccination and influencing factors” has been published in Nature Communications. Svend Andersen Research Foundation, Carlsberg Foundation and The Novo Nordisk Foundation awarded a grant of DKK 4,803,750 to Peter Garred for The Copenhagen SARS-CoV-2 Antibody Testing Initiative. The article is a part of the VACCIM initiative, which investigates SARS-CoV-2 vaccine immune responses among hospital professionals and patients at Rigshospitalet and Herlev & Gentofte University Hospital.

Peter Garred leads a research group at Rigshospitalet and the University of Copenhagen. He tries to understand the structure, molecular genetics and c...

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