People who have recovered from COVID-19 had a robust antibody response after the first dose of the mRNA vaccine, but little immune benefit after the second dose, according to new research from the Penn Institute of Immunology. The results, published today in Scientific immunologysuggest that a single dose of vaccine may be needed to produce a sufficient antibody response. The team found that those who did not have COVID-19 – called naive COVID – did not have a complete immune response until they received their second dose of the vaccine, reinforcing the importance of completing both recommended doses to achieve high levels of immunity.
The study provides more information on the underlying immunobiology of mRNA vaccines, which could help shape future vaccine strategies.
“These results are encouraging for the efficacy of the vaccines in the short and long term, and it adds to our understanding of the immune response of the mRNA vaccine through memory B cell analysis,” said lead author E. John Wherry, PhD, chair of the Department of Systems Pharmacology and Translational Therapy and Director of the Penn Institute of Immunology at the Perelman School of Medicine at the University of Pennsylvania.
The human immune response to vaccines and infections leads to two major results: the production of antibodies that provide rapid immunity and the creation of memory B cells, which contribute to long-term immunity. This study represents one of the first to discover how memory B cell responses differ after vaccination in people who have previously suffered from an infection, compared to those who do not have COVID-19.
“Previous studies of COVID-19 mRNA vaccines in vaccinated individuals have focused on antibodies more than memory B cells. Memory B cells are a strong predictor of future antibody responses, which is why it is vital to measure B cell responses to these vaccines, ”said Wherry. “This effort to examine memory B cells is important for understanding long-term protection and the ability to respond to variants.”
Researchers recruited 44 healthy people who received the BioNTech / Pfizer or Moderna mRNA COVID-19 vaccine at the University of Pennsylvania Health System. Of this cohort, 11 had a previous infection with COVID-19. Blood samples were taken for deep immune analyzes four times before and after the vaccine doses.
The data show key differences in vaccine immune responses in COVID-naive individuals compared to individuals recovered from COVID-19. The results suggest that a single dose of vaccine in individuals recovered from COVID-19 may be sufficient to induce a maximal immune response, based on both strong antibodies and memory B cell responses. This is probably due to a primary immune response due to their natural infection.
In contrast, it took two doses of the vaccine to demonstrate considerable antibody and memory B cell responses for those who did not have COVID-19, which underlies the importance of the two-dose vaccination schedule. MRNA to achieve optimal levels of immunity.
These results were also reflected in an analysis of antibodies against the D614G mutation and the South African variant B.1.351 of COVID-19. For those who did not have COVID-19, it took a second dose to achieve a sufficiently robust level of immunity against the mutation and variant, while those recovered from COVID-19 had a sufficiently strong antibody response after one dose. .
“It is important that we keep this in mind when considering future vaccination strategies and potential viral variants,” Wherry said. “We need to make sure people have the strongest memory B cell responses available. If circulating antibodies decline over time, our data suggests that long-lasting memory B cells could provide a rapid source of protection against re-exposure to COVID-19, including variants. “
The researchers also looked at side effects induced by the vaccine in relation to immune responses. Although they were seen in a smaller cohort of 32 COVID-naive people, they found that those who experienced systemic side effects after receiving a dose of the vaccine – such as fever, chills, headache head and fatigue – had stronger serum antibodies after vaccination, but no memory B cells. Although more data is needed and all subjects developed robust immunity, it is possible that inflammation and Early side effects after vaccination may signal stronger immune reactions.
“Everyone has good answers to vaccines. They work to protect people from COVID-19. But for those who may worry about side effects, they aren’t necessarily a bad thing – they can actually be an indicator of an even better immune system. response, ”Wherry said.
Researchers are continuing larger-scale studies, which are needed to fully examine the issue of a one- or two-dose regimen in individuals recovered from COVID-19 and to see how long the vaccine antibodies last. Wherry and his team continue to study the vaccine’s effect on virus-specific T cell responses, another part of the body’s immune response.
The study was facilitated by the Penn Immune Health Project, with funding from NIH (AI105343, AI082630, AI108545, AI155577, AI149680, AI152236, HL143613, P30-AI0450080, T32 AR076951-01, T32 CA009140, T32 AI055400, U19AI0830) , the Allen Institute for Immunology, Research Institute-Mark Foundation Cancer Fellowship, Chen Family Research Fund, Parker Institute for Cancer Immunotherapy, Penn Center for Research on Coronavirus and Other Emerging Pathogens, University of Pennsylvania Perelman School of Medicine COVID Fund, the University of Pennsylvania Perelman School of Medicine 21st Century Scholar Fund and a philanthropic donation from Jeffrey Lurie, Joel Embiid, Josh Harris and David Blitzer.