Persistence of immunity against Omicron BA.1 and BA.2 variants following homologous and heterologous COVID-19 booster vaccines in healthy adults after a two-dose AZD1222 vaccination.

• The messenger RNA (mRNA) booster produced a high cross-neutralization level against the Omicron variant. • The half-dose mRNA-1273 elicited total immunoglobulin (Ig) and anti-receptor-binding domain IgG equal to the full dose. • The neutralizing activity thwarting the BA.1 and BA.2 variants was comparable in the mRNA booster. • Clusters of differentiation (CD), CD4+ and CD8+ T cell responses were restored after the mRNA booster vaccination. • The additional fourth dose should be implemented for AZD1222-boosted individuals. The SARS-CoV-2 Omicron variant presents numerous mutations potentially able to evade neutralizing antibodies (NAbs) elicited by COVID-19 vaccines. Therefore, this study aimed to provide evidence on a heterologous booster strategy to overcome the waning immunity against Omicron variants. Participants who completed the Oxford/AstraZeneca (hereafter AZD1222) vaccine dose for 5-7 months were enrolled. The reactogenicity and persistence of immunogenicity in both humoral and cellular response after a homologous or heterologous booster with the AZD1222 and messenger RNA (mRNA) vaccines (BNT162b2, full, or half-dose mRNA-1273) administered 6 months after primary vaccination were determined. A total of 229 individuals enrolled, and waning of immunity was observed 5-7 months after the AZD1222-primed vaccinations. Total receptor-binding domain (RBD) immunoglobulin (Ig) levels, anti-RBD IgG, and focus reduction neutralization test against Omicron BA.1 and BA.2 variants and T cell response peaked at 14-28 days after booster vaccination. Both the full and half dose of mRNA-1273 induced the highest response, followed by BNT162b2 and AZD1222. At 90 days, the persistence of immunogenicity was observed among all mRNA-boosted individuals. Adverse events were acceptable for all vaccines. A heterologous mRNA booster provided a significantly superior boost of binding and NAbs levels against the Omicron variant compared with a homologous booster in individuals with AZD1222-primed vaccinations. [ABSTRACT FROM AUTHOR]