Vaccines alone may not be enough to protect people with weakened immune systems from Covid-19, according to new research by the University of Cambridge. The study, published in Science Advances, indicates that immunocompromised individuals need regular booster doses to maintain protection and reduce the risk of severe infections and the emergence of new variants.
The global impact of Covid-19 has been significant, with almost 16 million deaths estimated in 2020 and 2021. However, rapid vaccine rollout is believed to have prevented nearly 20 million additional deaths during that period.
Immunocompromised people often have trouble clearing the virus even after vaccination. This group includes those whose immune systems are weakened due to disease or medications such as immunosuppressants used for organ transplant recipients. As a result, their infections can last longer, providing more opportunities for the virus to mutate.
Previous research early in the pandemic showed that long-lasting infections could lead to new variants that might cause fresh waves of infection in the general population.
Vaccination triggers an immune response called seroconversion, where antibodies target the virus. Booster shots increase this response and improve chances of clearing infection. Despite most immunocompromised individuals receiving three or more vaccine doses, they still represent over one-fifth of hospitalizations, intensive care admissions, and deaths related to Covid-19.
Researchers at the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) studied vaccinated patients with vasculitis—a condition treated with drugs like rituximab that lower B-cell counts responsible for producing antibodies. Blood samples from these patients revealed that seroconversion did not always neutralize the virus effectively. All immunocompromised participants required at least three vaccine doses for protection against several variants up to Omicron; some needed four doses but still lacked sufficient protection.
Kimia Kamelian from CITIID stated: "We know that immunocompromised individuals are particularly vulnerable to diseases such as Covid-19 because their immune systems struggle to clear infections. Vaccinations offer some protection, but our study shows that only repeated vaccinations - often four or more - offer the necessary protection."
Professor Ravi Gupta added: "This of course has implications for the individual, who is more likely to have prolonged infection and a much greater risk of severe infection, but it also gives the virus multiple opportunities to mutate.
"We know from our previous work that at least some of the variants of concern probably emerged during chronic infections. That's why these individuals must be given priority for updated vaccines against new variants."
Funding for this research was provided by Wellcome, Gates Cambridge, Addenbrooke's Charitable Trust and Vasculitis UK, along with support from the National Institute for Health and Care Research Cambridge Biomedical Research Centre.
