In brief

CoronaVac booster shots trigger protective memory B cell and T cell responses to shield against COVID-19, but patients still risk breakthrough infections by the Omicron variant.

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Putting vaccine booster alternatives to the test

24 May 2023

Inactivated COVID-19 vaccines could be an equally potent alternative for people with allergic sensitivities to mRNA-based vaccines.

The COVID-19 pandemic saw the rise of a new class of vaccines: ones that use mRNA to teach our immune systems how to fend off the virus. Since then, billions of mRNA-based vaccine doses have been given worldwide, boosting protection against COVID-19. However, for a few, those vaccines may trigger allergy-like reactions ranging from mild rash to potentially life-threatening breathing difficulties.

Anyone with such reactions after an initial mRNA shot is generally ineligible for further doses, explains Yun Shan Goh, a Senior Research Scientist from the A*STAR Infectious Diseases Labs (ID Labs). Instead, they’re recommended non-mRNA-based alternatives for booster doses. These include inactivated virus vaccines like CoronaVac, which train the immune system to recognise an infection by exposing it to inert forms of the virus. This differs from mRNA vaccines, which show the immune system how to make copies of viral surface proteins to practice on.

While inactivated vaccines have been used for centuries, Goh and colleagues wanted to test if CoronaVac was an effective alternative to mRNA COVID-19 vaccine boosters. The team, in collaboration with clinicians from various Singaporean hospitals, recruited 105 participants with a history of allergic reactions to such vaccines. They treated some participants with a CoronaVac booster and then tracked their immune responses through antibody, memory B cell and T cell levels.

Compared to the control group receiving mRNA boosters, participants who received the CoronaVac booster produced lower levels of antibodies against the virus’s spike protein. However, to the researchers’ surprise, the levels of antibody-producing memory B cells and virus-killing T cells were comparable between both groups.

“There was no direct evidence that Coronavac’s mechanism of action reduces the risk of such reactions,” said Goh. “However, the data showed that for individuals with limited vaccine options due to excessive allergic reactions to mRNA vaccines, CoronaVac can be an alternative.”

Unfortunately, new SARS-CoV-2 variants such as the Omicron variant pose an added challenge. Goh’s team found that neither mRNA nor CoronaVac boosters offered sufficiently protective immune responses against Omicron.

“Variant-specific immunity remains low following CoronaVac vaccination, similar to mRNA vaccination,” said Goh, adding that additional boosters may be required to shield against Omicron and its subvariants. “Apart from CoronaVac, other non-mRNA vaccines such as the protein-based NVX-CoV2373 should be investigated as an alternative for those with allergic reactions.”

The team is currently building upon their findings by examining how long immune responses to CoronaVac vaccines last and whether additional boosters could extend the vaccine’s protective effects, especially against new variants.

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

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Goh, Y.S., Fong, S.-W., Rouers, A., Chang, Z.W., Tay, M.Z., et al. Heterologous booster vaccination with CoronaVac following prime vaccination with mRNA vaccine. Clinical & Translational Immunology 11, e1403 (2022). | article

About the Researchers

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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.
Yun Shan Goh received her PhD degree from the University of Cambridge (UK) studying antibody response against invasive Salmonella. Goh expanded the research focus to African diseases including Meningococcal meningitis during her postdoctoral training at the Novartis Vaccine Institute for Global Health (Italy) and Wellcome Trust Sanger Institute (UK), where she received a Marie Curie Fellowship. Since joining A*STAR’s Singapore Immunology Network and then A*STAR Infectious Diseases Labs, Goh has been studying antibody-mediated protection in malarial infections and identifying potential correlates of protections.

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