title: Investigating the effect of AS03 adjuvant on the plasma cell repertoire following pH1N1 influenza vaccination.
abstract: Influenza pandemics require rapid deployment of effective vaccines for control. Adjuvants such as AS03 improve vaccine immunogenicity, but this mechanism is poorly understood. We used high-throughput B cell receptor sequencing of plasma cells produced following AS03-adjuvanted and non-adjuvanted 2009 pandemic H1N1 vaccination, as well as pre-pandemic seasonal influenza vaccination to elucidate the effect of the adjuvant on the humoral immune response. By analyzing mutation levels, it was possible to distinguish sequences from cells that were recently activated from naïve B cells from those that were activated by memory recall. We show that the adjuvant functions through two mechanisms. First, the adjuvant stimulates increased activation of naïve B cells, thus reducing immune interference with previous vaccine responses. Second, the adjuvant is able to increase the adaptability of the recalled cells to give improved specificity to the new vaccine antigen. We thus show how AS03 enhances pH1N1 immune responses, and reduces immune interference.
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Center, Oxford, United Kingdom.
authors.forename: J D
authors.initials: JD
authors.lastname: Galson
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Center, Oxford, United Kingdom.|Paediatric Immunology, University Children's Hospital Zürich, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Trück
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Center, Oxford, United Kingdom.
authors.forename: D F
authors.initials: DF
authors.lastname: Kelly
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: van der Most
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004311:Double-Blind Method; D004338:Drug Combinations; D006801:Humans; D007115:Immunization Schedule; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D007251:Influenza, Human / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D011136:Polysorbates / Q000008:administration & dosage; D013185:Squalene / Q000008:administration & dosage; D014611:Vaccination / Q000379:methods*; D024502:alpha-Tocopherol / Q000008:administration & dosage
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D004338:Drug Combinations; D007252:Influenza Vaccines; D011136:Polysorbates; D013185:Squalene; C550253:AS03 adjuvant; D024502:alpha-Tocopherol