In brief

Individuals who received mRNA-based booster shots had higher levels of neutralising IgG antibodies targeting the receptor-binding domain of SARS-CoV-2 offering enhanced protection against infections.

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mRNA boosters: our best bet against Omicron?

12 Apr 2023

Booster shots with COVID-19 mRNA outperformed inactivated virus by eliciting stronger antibody responses to the Omicron variant.

The SARS-CoV-2 Omicron variant burst onto the world stage in late 2021 before completely changing the trajectory of the pandemic. Spreading faster than its predecessor, the Delta variant, Omicron triggered a surge in case numbers and hospitalisations even among the vaccinated. In response, public health authorities quickly initiated vaccine booster rollouts to protect vulnerable communities.

Overall, vaccination regimens varied widely around the world-some countries opted for mRNA-based primer vaccines and boosters, while others offered vaccines made from inactivated SARS-CoV-2, such as Sinovac’s CoronaVac. However, the relative levels of immune protection created by these two vaccine types—and prime-booster combinations of both—remained unknown.

Shengli Xu, Principal Investigator at A*STAR’s Singapore Immunology Network (SIgN), said that Singapore was uniquely positioned to provide answers to this black box as one of the first countries to make both mRNA and inactivated virus vaccines available.

"We had the advantage of studying the immune response in a single ethnic group (Singaporean Chinese) upon immunisation with different vaccines,” explained Xu.

In collaboration with Genscript, Doctors for Life Medical and Miltenyi Biotec, Xu and colleagues studied antibody responses against Omicron in 66 healthy participants who had received different combinations of COVID-19 prime and booster vaccinations. According to Xu, measuring levels of neutralising antibodies (or those that prevent the coronavirus from infecting human cells) is a good proxy for protection against COVID-19.

The researchers found that, regardless of the prime vaccine involved, past recipients of mRNA-based boosters had at least 17 times the levels of antibodies targeting Omicron’s spike (S) protein versus those with inactivated virus boosters—a sign of stronger protection against the variant.

These results suggest that mRNA-based boosters may have better life-saving potential against COVID-19 than inactivated virus vaccines.

One possible explanation for these findings is the difference in target specificity offered by these vaccines. “We hypothesised that the mRNA vaccine could induce a more diverse antibody repertoire to target different S protein variants, including Omicron,” elaborated Xu.

In upcoming studies, the team plans to investigate the correlation between vaccine regimen and S protein-specific antibody repertoires in more detail to provide insights that may support future public health policies.

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

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Zhang, B., Huo, J., Huang, Y., Teo, S.Y., Duan, K., et al. mRNA Booster Vaccination Enhances Antibody Responses against SARS-CoV2 Omicron Variant in Individuals Primed with mRNA or Inactivated Virus Vaccines. Vaccines 10, 1057 (2022). | article

About the Researchers

Shengli Xu joined the Institute of Molecular and Cell Biology (IMCB), Singapore, beginning his PhD studies in 1998. Upon obtaining his PhD in Immunology in 2003, Xu pursued postdoctoral research, first as a Research Fellow at IMCB, and later as a Senior Research Fellow at Singapore Immunology Network (SIgN) until 2009. In 2009, he joined Bioprocessing Technology Institute (BTI) as a Research Scientist and progressed to become a Senior Lead Research Scientist and a Group Leader. In 2020, Xu rejoined SIgN as a Principal investigator to lead the B Cell Immunology Group. He is also an adjunction assistant professor at the Department of Physiology, NUS. Xu’s research primarily focuses on B-cell immunology and the development of antibody-based immunotherapy.
Kong-Peng Lam obtained his PhD in Immunology in 1994 from the College of Physicians & Surgeons at Columbia University, US. He then carried out postdoctoral research at the Institute for Genetics, University of Cologne, working to understand B cell biology and development. He is currently the Executive Director of A*STAR’s Singapore Immunology Network (SIgN), a Professor in the Departments of Microbiology and Immunology, Physiology, and Pediatrics at Yong Loo Lin School of Medicine, National University of Singapore (NUS), and an Adjunct Professor in the School of Biological Sciences at Nanyang Technological University (NTU).
Biyan Zhang graduated from National University of Singapore with a BSc in Life Sciences in 2013 and completed her PhD studies in Immunobiology at Yale University, USA, in 2020. During her PhD, Zhang focused on understanding the immunological mechanisms that promote or mitigate food allergy under the guidance of Stephanie Eisenbarth. Currently, Zhang is conducting postdoctoral studies at the Prof Lam Kong Peng Lab in SIgN. She is interested in understanding the factors that regulate B cell responses to vaccines and allergens.

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