This longitudinal cohort study in Malaysia investigated humoral and T cell immune responses after primary and homologous or heterologous booster vaccinations and breakthrough infection. Vaccinated post-COVID-19 individuals showed higher and more durable neutralizing antibodies against SARS-CoV-2 wild type (WT) and Omicron spikes but similar declining T cell responses compared to uninfected vaccinated individuals. Two doses of BNT162b2 induced higher neutralizing antibodies against WT and T cell responses than ChAdOx1-S for six months. The BNT162b2 booster conferred a greater humoral response against WT but similar cross-neutralizing antibody against Omicron and T cell responses in the homologous booster group compared to the heterologous booster group. Breakthrough infection in the homologous booster group significantly increased neutralizing antibodies, but T cell responses remained low. The findings suggest that both homologous and heterologous vaccination regimes are effective, offering flexibility in vaccine administration.

J Y L Fu, M H Pukhari, M K Bador, I-C Sam, Y F Chan, Zhenglun Liang, Qunying Mao, Jolene Yin, Ling Fu