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Medientyp:
E-Artikel
Titel:
Homologous but not heterologous COVID-19 vaccine booster elicits IgG4+ B-cells and enhanced Omicron subvariant binding
Beteiligte:
Hartley, Gemma E.;
Fryer, Holly A.;
Gill, Paul A.;
Boo, Irene;
Bornheimer, Scott J.;
Hogarth, P. Mark;
Drummer, Heidi E.;
O’Hehir, Robyn E.;
Edwards, Emily S. J.;
van Zelm, Menno C.
Erschienen:
Springer Science and Business Media LLC, 2024
Erschienen in:
npj Vaccines, 9 (2024) 1
Sprache:
Englisch
DOI:
10.1038/s41541-024-00919-8
ISSN:
2059-0105
Entstehung:
Anmerkungen:
Beschreibung:
AbstractBooster vaccinations are recommended to improve protection against severe disease from SARS-CoV-2 infection. With primary vaccinations involving various adenoviral vector and mRNA-based formulations, it remains unclear if these differentially affect the immune response to booster doses. We examined the effects of homologous (mRNA/mRNA) and heterologous (adenoviral vector/mRNA) vaccination on antibody and memory B cell (Bmem) responses against ancestral and Omicron subvariants. Healthy adults who received primary BNT162b2 (mRNA) or ChAdOx1 (vector) vaccination were sampled 1-month and 6-months after their 2nd and 3rd dose (homologous or heterologous) vaccination. Recombinant spike receptor-binding domain (RBD) proteins from ancestral, Omicron BA.2 and BA.5 variants were produced for ELISA-based serology, and tetramerized for immunophenotyping of RBD-specific Bmem. Dose 3 boosters significantly increased ancestral RBD-specific plasma IgG and Bmem in both cohorts. Up to 80% of ancestral RBD-specific Bmem expressed IgG1+. IgG4+ Bmem were detectable after primary mRNA vaccination, and expanded significantly to 5–20% after dose 3, whereas heterologous boosting did not elicit IgG4+ Bmem. Recognition of Omicron BA.2 and BA.5 by ancestral RBD-specific plasma IgG increased from 20% to 60% after the 3rd dose in both cohorts. Reactivity of ancestral RBD-specific Bmem to Omicron BA.2 and BA.5 increased following a homologous booster from 40% to 60%, but not after a heterologous booster. A 3rd mRNA dose generates similarly robust serological and Bmem responses in homologous and heterologous vaccination groups. The expansion of IgG4+ Bmem after mRNA priming might result from the unique vaccine formulation or dosing schedule affecting the Bmem response duration and antibody maturation.