Waning immunity and IgG4 responses following bivalent mRNA boosting.

Autor: Lasrado N; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Collier AY; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Miller J; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Hachmann NP; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Liu J; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Anand T; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., A Bondzie E; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Fisher JL; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Mazurek CR; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Patio RC; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Rodrigues SL; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Rowe M; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Surve N; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Ty DM; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Wu C; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Chicz TM; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA., Tong X; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA., Korber B; Los Alamos National Laboratory and New Mexico Consortium, Los Alamos, NM, USA., McNamara RP; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA., Barouch DH; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2024 Feb 23; Vol. 10 (8), pp. eadj9945. Date of Electronic Publication: 2024 Feb 23.
DOI: 10.1126/sciadv.adj9945
Abstrakt: Messenger RNA (mRNA) vaccines were highly effective against the ancestral SARS-CoV-2 strain, but the efficacy of bivalent mRNA boosters against XBB variants was substantially lower. Here, we show limited durability of neutralizing antibody (NAb) responses against XBB variants and isotype switching to immunoglobulin G4 (IgG4) responses following bivalent mRNA boosting. Bivalent mRNA boosting elicited modest XBB.1-, XBB.1.5-, and XBB.1.16-specific NAbs that waned rapidly within 3 months. In contrast, bivalent mRNA boosting induced more robust and sustained NAbs against the ancestral WA1/2020 strain, suggesting immune imprinting. Following bivalent mRNA boosting, serum antibody responses were primarily IgG2 and IgG4 responses with poor Fc functional activity. In contrast, a third monovalent mRNA immunization boosted all isotypes including IgG1 and IgG3 with robust Fc functional activity. These data show substantial immune imprinting for the ancestral spike and isotype switching to IgG4 responses following bivalent mRNA boosting, with important implications for future booster designs and boosting strategies.
Databáze: MEDLINE