Distinct COVID-19 vaccine combinations result in divergent immune responses

Abstract

Waning antibody responses after COVID-19 vaccination combined with the emergence of the SARS-CoV-2 Omicron lineage led to reduced vaccine effectiveness. As a countermeasure, bivalent mRNA-based booster vaccines encoding the ancestral spike protein in combination with that of Omicron BA.1 or BA.5 were introduced. Since then, BA.2-descendent lineages have become dominant, such as XBB.1.5 or BA.2.86. Here, we assessed how different COVID-19 priming regimens affect the immunogenicity of the recently used bivalent booster vaccinations and breakthrough infections. BA.1 and BA.5 bivalent vaccines boosted neutralizing antibodies and T-cells up to 3 months after boost; however, cross-neutralization of XBB.1.5 was poor. Interestingly, different combinations of prime-boost regimens induced divergent responses: participants primed with Ad26.COV2.S developed lower binding antibody levels after bivalent boost while neutralization and T-cell responses were similar to mRNA-based primed participants. In contrast, the breadth of neutralization was higher in mRNA-primed and bivalent BA.5 boosted participants. Combined, we highlight important "lessons learned" from the employed COVID-19 vaccination strategies. Our data further support the use of monovalent vaccines based on circulating strains when vaccinating risk groups, as recently recommended by the WHO. We emphasize the importance of the continuous assessment of immune responses targeting circulating variants to guide future COVID-19 vaccination policies.

Bivalent COVID-19 vaccines boost the capacity of pre-existing SARS-CoV-2-specific memory B cells to cross-recognize Omicron subvariants

“…This finding aligns with trials of the mRNA-1273.214 BA.1 bivalent vaccine, which was found to elicit superior NAb titers against its target antigen, Omicron BA.1, compared to the monovalent mRNA-1273 vaccine ( 15, 16 ). We also found that the BA.5 bivalent booster broadened variant NAb recognition the most, eliciting higher BA.5 NAb titers than the BA.1 bivalent and monovalent boosters, which confirms previous findings for this vaccine ( 14, 15, 38–40 ).…”

“…The WH1, BA.1, and BA.5 NAb titers of the bivalent vaccine recipients in our report displayed similar patterns as those from the SWITCH-ON trial ( 30, 38 ). We here extended these findings to report that both bivalent boosters elicited greater antibody responses than a monovalent booster, resulting in higher BA.1 and BA.5 NAb titers.…”

“…NAb were measured for all donor plasma samples using a plaque reduction neutralization test (PRNT), as described previously ( 5, 30, 59 ). Viruses were isolated and cultured from clinical specimens from the Department of Viroscience, Erasmus MC, and confirmed by next-generation sequencing: D614G (ancestral; GISAID: hCov-19/Netherlands/ZH-EMC-2498), Omicron BA.1 (GISAID: hCoV-19/Netherlands/LI-SQD-01032/2022), and Omicron BA.5 (EVAg: 010V-04723; hCovN19/Netherlands/ZHNEMCN5892) ( 38 ). Briefly, heat-inactivated serum was serially diluted two-fold in OptiMEM without FBS (Gibco).…”