Por favor, use este identificador para citar o enlazar este ítem: http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/8257
Third dose COVID-19 mRNA vaccine enhances IgG4 isotype switching and recognition of Omicron subvariants by memory B cells after mRNA but not adenovirus priming
Gemma Hartley
Holly Fryer
Paul Gill
Irene Boo
Mark Hogarth
Heidi Drummer
Robyn O'Hehir
Emily Edwards
Menno van Zelm
Acceso Abierto
Atribución-NoComercial-SinDerivadas
https://doi.org/10.1101/2023.09.15.557929
https://www.biorxiv.org/content/10.1101/2023.09.15.557929v2
Background Booster 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 here 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. Methods Healthy adults who received primary BNT162b2 (mRNA) (n=18) or ChAdOx1 (vector) (n=25) 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. Results 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. Conclusion 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.
bioRxiv
19-09-2023
Preimpreso
Inglés
Público en general
VIRUS RESPIRATORIOS
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