Waning immunity and IgG4 responses following bivalent mRNA boosting

• DOI: 10.1126/sciadv.adj9945
• Publication Date: 2024-02-23T18:58:45Z
• Authors: 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. Rodri...; Marjorie Rowe; Nehalee Surve; Darren M. Ty; Cindy Wu; Taras M. Chicz; Xin Tong; Bette Korber; Ryan P. McNamara; Dan H. Barouch
• Keywords: Bivalent (engine); Isotype; Boosting

Messenger RNA (mRNA) vaccines were highly effective against the ancestral SARS-CoV-2 strain, but efficacy of bivalent mRNA boosters XBB variants was substantially lower. Here, we show limited durability neutralizing antibody (NAb) responses and isotype switching to immunoglobulin G4 (IgG4) following boosting. Bivalent boosting elicited modest XBB.1-, XBB.1.5-, XBB.1.16-specific NAbs that waned rapidly within 3 months. In contrast, induced more robust sustained WA1/2020 suggesting immune imprinting. Following boosting, serum primarily IgG2 IgG4 with poor Fc functional activity. a third monovalent immunization boosted all isotypes including IgG1 IgG3 These data substantial imprinting for spike important implications future booster designs strategies.