Immunity of heterologous and homologous boosted or convalescent individuals against Omicron BA.1, BA.2 and BA.4/5 variants.

BACKGROUND: The emerged SARS-CoV-2 Omicron variants BA.1, BA.2 and BA.4/5 demonstrate higher transmission and infection compared to previous variants of concern. To evaluate effectiveness of heterologous and homologous booster vaccination, we directly compared cellular and humoral immune responses as well as neutralizing capacity against replication-competent SARS-CoV-2 wild type, Delta and Omicron variants BA.1, BA.2, BA.4/5.

METHODS: For this, peripheral blood mononuclear cells (PBMCs) and serum samples of 137 participants divided into three major groups were investigated. Individuals of the first group were twice ChAdOx1 vaccinated and mRNA (BNT162b2 or mRNA-1273)-boosted, the second group included triple mRNA vaccinated participants and the third group consisted of twice vaccinated and convalescent individuals.

RESULTS: Vaccination and convalescence resulted in the highest levels of SARS-CoV-2-specific antibodies, stronger T cell responses and best neutralization against WT, Delta Omicron BA.2 and BA.4/5, while a combination of twice ChAdOx1 and BNT162b2-vaccinated regimen displayed elevated neutralizing capacity against Omicron BA.1. In addition, heterologous boosted individuals showed higher efficacy against Omicron BA.2 as well as BA.4/5 compared to homologous booster regimens.

CONCLUSIONS: We here showed that twice vaccinated and convalescent individuals demonstrated the strongest immunity against Omicron BA.2 and BA.4/5 variant followed by heterologous and homologous booster vaccine regimens.