Vaccinations alone may not protect immunocompromised patients, Cambridge research shows

Vaccinations alone may not protect immunocompromised patients, Cambridge research shows

Vaccinations alone may not be enough to protect people with compromised immune systems from infection, even if the vaccine has caused the production of antibodies, new research from the University of Cambridge has shown.

The results published today inScience advancesSuggest that such people need regular vaccine boosters to protect them and reduce the risk of infections, which could be serious and also lead to new “variants of concern.”

It is estimated that nearly 16 million people worldwide died from Covid-19 in 2020 and 2021, despite what was believed to be the pandemic.

During the pandemic, researchers found that immunocompromised people had difficulty clearing the virus even when they were vaccinated. These are people whose immune systems are not functioning properly, either as a direct result of illness or because they have medications to suppress their immune systems, for example to prevent organ transplant rejection. This meant their infections lasted longer and gave the virus more opportunities to mutate.

Research from early in the pandemic showed that chronic infections can lead to variants of concern, which can then cause new waves of infections in the broader population.

When a person is vaccinated, their immune systems produce antibodies that recognize and launch an attack on the virus. Such a process is called seroconversion. Additional 'booster' vaccinations increase seroconversion and therefore the likelihood of clearing infections.

Although most immunocompromised people have received three or more doses of the CoVID-19 vaccine, they still account for more than a fifth of hospitalizations, intensive care unit admissions and overall deaths associated with the disease.

To see why this is the case, scientists at the University of Cambridge's Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) studied immunocompromised people who had been vaccinated against Covid-19. These patients, recruited from Cambridge University NHS Foundation Trust, were living with vasculitis, a group of disorders that cause inflammation of blood vessels. Data from this group were compared with people who were not immunocompromised.

Treatments for vasculitis rely on immunosuppressive medications. These include drugs like rituximab, which deplete the number of B cells in the body - but B cells are the immune cells responsible for making antibodies. As such, these individuals represent a highly vulnerable population.

When the researchers analyzed blood samples from the vasculitis patients, they found that although the vaccination induced seroconversion, this in itself was not always enough to neutralize the virus. Each immunocompromised person needed at least three doses of the vaccine to protect them across a range of variants up to Omicron (the variant that appeared towards the end of 2021 and caused a new wave of infections). In some cases, even four vaccinations were not enough to adequately protect them.

Kimia Kamelian, a Tore Cambridge scholar at Citiid and St Edmund's College, Cambridge, said: "We know that immunocompromised individuals are particularly vulnerable to diseases like Covid-19. The study shows that only repeated vaccinations - often four or more - provide the necessary protection."

Professor Ravi Gupta, also from Citiid and a fellow at Homerton College, Cambridge, added: “This obviously has implications for the individual, who is more likely to have a longer virus in multiple ways to mutate.

We know from our previous work that at least some of the variants of concern likely arose in chronic infections. For this reason, these people must be prioritized for updated vaccines against new variants. “

Ravi Gupta, Professor, University of Cambridge

The research was funded by Wellcome, Gates Cambridge, Addenbrooke's Charitable Trust and Vasculitis UK, with additional support from the National Institute for Health and Care Research Cambridge Biomedical Research Center.

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