Humoral and cellular response induced by a second booster of an inactivated SARS-CoV-2 vaccine in adults

The Omicron variant has challenged the control of the COVID-19 pandemic due to its immuno-evasive properties. The administration of a booster dose of a SARS-CoV-2 vaccine showed positive effects in the immunogenicity against SARS-CoV-2, effect that is even enhanced after the administration of a second booster.

During a phase-3 clinical trial, we evaluated the effect of a second booster of CoronaVac®, an inactivated vaccine administered 6 months after the first booster, in the neutralization of SARS-CoV-2 (n = 87). In parallel, cellular immunity (n = 45) was analyzed in stimulated peripheral mononuclear cells by flow cytometry and ELISPOT.

Although a 2.5-fold increase in neutralization of the ancestral SARS-CoV-2 was observed after the second booster when compared with prior its administration (Geometric mean units p < 0.0001; Geometric mean titer p = 0.0002), a poor neutralization against the Omicron variant was detected. Additionally, the activation of specific CD4⁺ T lymphocytes remained stable after the second booster and, importantly, equivalent activation of CD4⁺ T lymphocytes against the Omicron variant and the ancestral SARS-CoV-2 were found.

Although the neutralizing response against the Omicron variant after the second booster of CoronaVac® was slightly increased, these levels are far from those observed against the ancestral SARS-CoV-2 and could most likely fail to neutralize the virus. In contrast, a robust CD4⁺T cell response may confer protection against the Omicron variant.

The Ministry of Health, Government of Chile, the Confederation of Production and Commerce, Chile and SINOVAC Biotech.NIHNIAID. The Millennium Institute on Immunology and Immunotherapy.