In brief

Heterologous vaccinations trigger strong memory B cell responses in older adults after receiving a booster shot.

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Mixing boosters strengthen vaccine protection

24 Apr 2023

An analysis of cellular immune responses reveals that mixing COVID-19 vaccines and boosters may offer enhanced protection for at-risk populations.

Most adults would struggle if presented with an exam paper from their secondary school days. Since those teenage years, memories of formulas and facts that were once quick to recall have likely faded.

It’s the same with vaccines, which can be thought of as ‘lessons’ for the immune system. Over time, a booster is needed to remind the body how to defend itself from viruses, especially when new information (in the form of variants) arises.

Protection derived from COVID-19 vaccines typically wanes around six months after the initial shot. Some studies suggest that those inoculated with a different booster than their first doses—known as a heterologous vaccination—may develop better antibody responses than those who received the same follow-up shot.

Antibodies are just one part of the immune system’s arsenal against viruses. “Immune responses are very complex and work as a big network,” explained Angeline Rouers, Senior Research Fellow at A*STAR Infectious Diseases Labs (ID Labs), who was interested in how boosters prime the cellular component of the immune system.

To answer this question, Rouers and colleagues worked with teams from A*STAR’s Singapore Immunology Network (SIgN); the National University of Singapore; the National Centre for Infectious Diseases, Singapore; Tan Tock Seng Hospital; and Nanyang Technological University to enlist 79 patients who had received a Moderna booster following two doses of the Pfizer-BioNTech (BNT162b2) vaccine.

The participants’ immune responses (including antibody levels, memory B cell and T cell responses) were measured immediately, seven days and 28 days after vaccination and were compared against those who had received three consecutive BNT162b2 shots.

Results from the team’s experiments lined up with previous reports that showed an uptick in neutralising antibody levels following heterologous vaccinations. Using a specialised assay called B cell ELISpot, the researchers explored the immune response more deeply and found that regardless of the regimen, booster shots also triggered an increase in memory B cells after 28 days.

According to Rouers, memory B cells work like antibody factories in case of re-exposure and can indicate of the person’s level of immune protection. “Memory B cells are responsible for antibody production when the immune system is recalled,” said Rouers.

“It is crucial to assess their presence and number to estimate the longevity of the immune response.”

Notably, compared to homologous vaccinations, heterologous ones led to significantly stronger memory B cell responses in adults aged over 60 years roughly 1 month after their third dose. This finding suggests that for seniors who are among those at risk of severe COVID-19 and death, recommending heterologous vaccinations might be a good public health strategy to keep them safe.

“These data will be helpful to guide policymaking and assist healthcare workers in deciding how to best immunise the vulnerable population,” Rouers added.

The team is expanding this work by testing different combinations of heterologous vaccinations as part of their mission to elucidate immune dynamics following COVID-19 boosters.

The A*STAR-affiliated researchers contributing to this research are from the A*STAR Infectious Diseases Labs (ID Labs) and the Singapore Immunology Network (SIgN).

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Rouers, A., Wong, N., Goh, Y.S., Torres-Ruesta, A., Tay, M.Z., et al. Efficient recall of SARS-CoV-2 variant-reactive B cells and T responses in the elderly upon heterologous mRNA vaccines as boosters. Journal of Medical Virology 95:e28258 (2022). | article

About the Researchers

Angeline Rouers is currently Senior Research Fellow at the A*STAR Infectious Diseases Labs under Prof Laurent Renia. She obtained a PhD in immunology from the Université Pierre et Marie Curie in Paris in 2016 by studying the impact of HIV infection on follicular helper T cells and memory B cell responses. She joined A*STAR in 2017 at the Singapore Immunology Network to study B cells and antibody response in dengue-infected patients. Since 2021, she has been pursuing her research at the newly settled A*STAR Infectious Diseases Labs. Her current research focus is on COVID-19 and mosquito-borne diseases such as dengue and malaria.
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Laurent Rénia

Senior Fellow and Principal Investigator

A*STAR Infectious Diseases Labs (ID Labs)
Laurent Rénia obtained his PhD in 1991 from University Pierre et Marie Curie (now Sorbonne University) in Paris, France and did his post-doctoral New York University (1991-1992). He then returned to Paris in 1993 where he obtained a permanent position as junior research scientist at the French National Institute of Health (INSERM) in the INSERM Unit 313 at the Hopital Pitie-Salpetriere in Paris. He moved to the INSERM Unit 445 at the Institut Cochin in Paris where he started his own group in 1997. In 2001-2006, he was the Research Director at INSERM, and Co-director and Director of the Department of Immunology at the Institut Cochin. He joined SIgN in 2007, where he was Executive Director from 2013 to 2020 before becoming the founding Executive Director of the A*STAR ID Labs from 2020 to 2021. He is now Professor of infectious Diseases and director of the respiratory and Infectious Diseases Program in Lee Kong Chian School of Medicine, Nanyang Technological University, as well as a Professor in the School of Biological Sciences at NTU and a Senior Fellow and Principal Investigator at A*STAR ID Labs. He also holds an adjunct position in the French National Institute of Health (INSERM). He has published more than 330 articles and book chapters and is an Academic Editor for Infection and Immunity, PLoS ONE, Infection and Immunity, Microbial Pathogenesis, Microbial cell and Frontiers in Immunology.

This article was made for A*STAR Research by Wildtype Media Group