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).