Heterologous inactivated virus/mRNA vaccination response to BF.7, BQ.1.1, and XBB.1

The emergence of highly immune-escape Omicron variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to concerns about the efficacy of vaccines and therapeutic monoclonal antibodies. Omicron subvariants BA.4.6, BF.7, BQ.1.1, XBB, and XBB.1 harbor the spike protein R346T substitution which contributes to evasion of class III anti-spike monoclonal antibody recognition while XBB, and XBB.1.1 subvariants harbor the F486S substitution which reduces binding for class I and II monoclonal antibodies.1 BQ.1, BQ.1.1, XBB, and XBB.1 are increasing rapidly in the United States, India, Europe, and other parts of the world, whereas BF.7 is one of the dominant strains currently circulating in China. Due to humoral immune imprinting, a phenomenon in which initial exposure to the original strain of SARS-CoV-2, by infection or vaccination, limits a person's future immune response against variants, the bivalent vaccine booster and hybrid immunity may not provide sufficient protection against emerging Omicron subvariants.2, 3, 4, 5, 6 We have previously shown that an mRNA vaccine booster in individuals vaccinated with two doses of inactivated vaccine significantly increased the level of plasma-neutralizing antibodies against Omicron BA.1.7 Whether this vaccination strategy retains neutralizing activity against the emerging Omicron subvariants remains unknown.