Neutralizing antibodies against the SARS-CoV-2 Delta and Omicron variants following heterologous CoronaVac plus BNT162b2 booster vaccination

TLDR

The recent emergence of the SARS‑CoV‑2 Omicron variant is raising concerns because of its increased transmissibility and numerous spike mutations that may evade neutralizing antibodies elicited by COVID‑19 vaccines. We evaluated the effects of a heterologous BNT162b2 mRNA vaccine booster on the humoral immunity of participants who had received a two‑dose regimen of CoronaVac, an inactivated vaccine used globally. The heterologous CoronaVac prime followed by a BNT162b2 booster produced high antibody titers and strong neutralization of the ancestral virus and Delta, comparable to two‑dose mRNA regimens, but only modestly increased Omicron neutralization (1.4‑fold) and still showed 7.1‑fold and 3.6‑fold reductions versus ancestral and Delta, underscoring the need for boosters in countries that used CoronaVac.

Abstract

The recent emergence of the SARS-CoV-2 Omicron variant is raising concerns because of its increased transmissibility and its numerous spike mutations, which have the potential to evade neutralizing antibodies elicited by COVID-19 vaccines. Here we evaluated the effects of a heterologous BNT162b2 mRNA vaccine booster on the humoral immunity of participants who had received a two-dose regimen of CoronaVac, an inactivated vaccine used globally. We found that a heterologous CoronaVac prime vaccination of two doses followed by a BNT162b2 booster induces elevated virus-specific antibody levels and potent neutralization activity against the ancestral virus and the Delta variant, resembling the titers obtained after two doses of mRNA vaccines. Although neutralization of Omicron was undetectable in participants who had received a two-dose regimen of CoronaVac, the BNT162b2 booster resulted in a 1.4-fold increase in neutralization activity against Omicron compared with the two-dose mRNA vaccine. Despite this increase, neutralizing antibody titers were reduced by 7.1-fold and 3.6-fold for Omicron compared with the ancestral strain and the Delta variant, respectively. These findings have immediate implications for multiple countries that previously used a CoronaVac regimen and reinforce the idea that the Omicron variant is associated with immune escape from vaccines or infection-induced immunity, highlighting the global need for vaccine boosters to combat the impact of emerging variants.