Bivalent Omicron BA.1 vaccine booster increases memory B cell breadth and neutralising antibodies against emerging SARS-CoV-2 variants

Current literature informs us that bivalent vaccines will generate a broader serum neutralizing antibody response to multiple SARS-CoV-2 variants, but studies on how this breadth relates to the memory B cell (MBC) and T cell responses are sparse. This study compared breadth of neutralising antibody, and memory B and T cell responses to monovalent or a bivalent ancestral/Omicron BA.1 COVID-19 booster vaccine. At baseline and 1-month post-booster, neutralisation activity and frequencies of receptor binding domain (RBD)-specific MBCs and Spike-specific memory T cells were measured against a panel of variants. Both vaccines boosted neutralising antibodies to 5 variants - Wuhan-Hu-1, Delta, BA.1, BA.5 and JN.1, the latter of which had not yet emerged at the time of sample collection. The bivalent vaccine induced a significantly larger increase in nAb against BA.1 and JN.1. Both vaccines boosted RBD-specific MBC responses to Wuhan-Hu-1, Delta, BA.1 and BA.5 variants with a significantly greater increase for BA.1 in the bivalent group. The breadth of MBCs was significantly higher in those who received the bivalent boost and correlated with nAb breadth. Both vaccines significantly boosted Spike-specific T cell responses to the Wuhan-Hu-1 and BA.5 variants, but only the bivalent vaccine boosted BA.1 responses. These results suggest that the bivalent vaccine confers an advantage against future novel variants due to increased frequency of broadly reactive RBD-specific B cells. Work supported by NSW Health for the NSW Vaccine, Infection and Immunology Collaborative (VIIM).