23 February 2024 | Ninaad Lasrado, Ai-ris Y. Collier, Jessica Miller, Nicole P. Hachmann, Jinyan Liu, Trisha Anand, Esther A. Bondzie, Jana L. Fisher, Camille R. Mazurek, Robert C. Patio, Stefanie L. Rodrigues, Marjorie Rowe, Nehalee Survé, Darren M. Ty, Cindy Wu, Taras M. Chicz, Xin Tong, Bette Korber, Ryan P. McNamara, Dan H. Barouch
The study investigates the durability and functional properties of neutralizing antibody (NAb) responses following bivalent mRNA boosting against SARS-CoV-2 variants, particularly the XBB subvariants. The results show that bivalent mRNA boosting elicits modest and transient NAb responses against XBB subvariants, with rapid waning within 3 months. In contrast, the ancestral WA1/2020 strain induces more robust and sustained NAb responses. Following bivalent mRNA boosting, serum antibody responses are primarily IgG2 and IgG4 with poor Fc functional activity. In contrast, a third monovalent mRNA immunization boosts all isotypes, including IgG1 and IgG3, with enhanced Fc functional activity. These findings suggest immune imprinting to the ancestral strain and significant isotype switching to IgG4 responses following bivalent mRNA boosting. The implications for future booster designs and strategies are discussed.The study investigates the durability and functional properties of neutralizing antibody (NAb) responses following bivalent mRNA boosting against SARS-CoV-2 variants, particularly the XBB subvariants. The results show that bivalent mRNA boosting elicits modest and transient NAb responses against XBB subvariants, with rapid waning within 3 months. In contrast, the ancestral WA1/2020 strain induces more robust and sustained NAb responses. Following bivalent mRNA boosting, serum antibody responses are primarily IgG2 and IgG4 with poor Fc functional activity. In contrast, a third monovalent mRNA immunization boosts all isotypes, including IgG1 and IgG3, with enhanced Fc functional activity. These findings suggest immune imprinting to the ancestral strain and significant isotype switching to IgG4 responses following bivalent mRNA boosting. The implications for future booster designs and strategies are discussed.