Maternal Antibodies Inhibit Neonatal and Infant Responses to Vaccination by Shaping the Early-Life B Cell Repertoire within Germinal Centers
Maria Vono,
Christiane Sigrid Eberhardt,
Floriane Auderset,
Beatris Mastelic-Gavillet,
Sylvain Lemeille,
Dennis Christensen,
Peter Andersen,
Paul-Henri Lambert,
Claire-Anne Siegrist
Affiliations
Maria Vono
WHO Collaborative Center for Vaccine Immunology, Department of Pathology and Immunology, University of Geneva, Geneva 1211, Switzerland; Corresponding author
Christiane Sigrid Eberhardt
WHO Collaborative Center for Vaccine Immunology, Department of Pathology and Immunology, University of Geneva, Geneva 1211, Switzerland
Floriane Auderset
WHO Collaborative Center for Vaccine Immunology, Department of Pathology and Immunology, University of Geneva, Geneva 1211, Switzerland
Beatris Mastelic-Gavillet
WHO Collaborative Center for Vaccine Immunology, Department of Pathology and Immunology, University of Geneva, Geneva 1211, Switzerland
Sylvain Lemeille
Department of Pathology and Immunology, University of Geneva, Geneva 1211, Switzerland
Dennis Christensen
Vaccine Adjuvant Research, Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen 2300, Denmark
Peter Andersen
Vaccine Adjuvant Research, Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen 2300, Denmark; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, 2300, Denmark
Paul-Henri Lambert
WHO Collaborative Center for Vaccine Immunology, Department of Pathology and Immunology, University of Geneva, Geneva 1211, Switzerland
Claire-Anne Siegrist
WHO Collaborative Center for Vaccine Immunology, Department of Pathology and Immunology, University of Geneva, Geneva 1211, Switzerland
Summary: Maternal antibodies (MatAbs) protect offspring from infections but limit their responses to vaccination. The mechanisms of this inhibition are still debated. Using murine early-life immunization models mimicking the condition prevailing in humans, we observed the induction of CD4-T, T follicular helper, and germinal center (GC) B cell responses even when early-life antibody responses were abrogated by MatAbs. GC B cells induced in the presence of MatAbs form GC structures and exhibit canonical GC changes in gene expression but fail to differentiate into plasma cells and/or memory B cells in a MatAb titer-dependent manner. Furthermore, GC B cells elicited in the presence or absence of MatAbs use different VH and Vk genes and show differences in genes associated with B cell differentiation and isotype switching. Thus, MatAbs do not prevent B cell activation but control the output of the GC reaction both quantitatively and qualitatively, shaping the antigen-specific B cell repertoire. : Maternal antibodies (MatAbs) protect offspring from infections but limit their vaccine responses through still poorly known mechanisms. Vono et al. report that MatAbs do not prevent B cell activation or germinal center formation but control plasma cell and memory B cell differentiation, shaping the long-term antigen-specific B cell repertoire. Keywords: immunization, maternal antibodies, neonates, repertoire, germinal centers, epitope masking
