AS03 adjuvant enhances the magnitude, persistence, and clonal breadth of memory B cell responses to a plant-based COVID-19 vaccine in humans.

Autor: Grigoryan L; Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA., Feng Y; Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA., Bellusci L; Food and Drug Administration, Silver Spring, MD 20993, USA., Lai L; Department of Pediatrics and Department of Microbiology and Immunology, Emory Vaccine Center, Emory National Primate Research Center, Emory School of Medicine, Atlanta, GA 30329, USA., Wali B; Department of Pediatrics and Department of Microbiology and Immunology, Emory Vaccine Center, Emory National Primate Research Center, Emory School of Medicine, Atlanta, GA 30329, USA., Ellis M; Department of Pediatrics and Department of Microbiology and Immunology, Emory Vaccine Center, Emory National Primate Research Center, Emory School of Medicine, Atlanta, GA 30329, USA., Yuan M; Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA 92037, USA., Arunachalam PS; Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA., Hu M; Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA., Kowli S; Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA., Gupta S; Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA., Maysel-Auslender S; Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA., Maecker HT; Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA., Samaha H; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA., Rouphael N; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.; Hope Clinic of Emory Vaccine Center, Emory University, Decatur, GA 30030, USA., Wilson IA; Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA 92037, USA., Moreno AC; Department of Medicine, Emory Vaccine Center, Emory National Primate Research Center, Emory University School of Medicine, Atlanta, GA 30329, USA., Suthar MS; Department of Pediatrics and Department of Microbiology and Immunology, Emory Vaccine Center, Emory National Primate Research Center, Emory School of Medicine, Atlanta, GA 30329, USA., Khurana S; Food and Drug Administration, Silver Spring, MD 20993, USA., Pillet S; Medicago Inc., Québec, QC G1V 3V9, Canada.; Research Institute of the McGill University Health Center, 1001 Decarie St., Montréal, QC H4A 3J1, Canada., Charland N; Medicago Inc., Québec, QC G1V 3V9, Canada., Ward BJ; Medicago Inc., Québec, QC G1V 3V9, Canada.; Research Institute of the McGill University Health Center, 1001 Decarie St., Montréal, QC H4A 3J1, Canada., Pulendran B; Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.
Jazyk: angličtina
Zdroj: Science immunology [Sci Immunol] 2024 Apr 05; Vol. 9 (94), pp. eadi8039. Date of Electronic Publication: 2024 Apr 05.
DOI: 10.1126/sciimmunol.adi8039
Abstrakt: Vaccine adjuvants increase the breadth of serum antibody responses, but whether this is due to the generation of antigen-specific B cell clones with distinct specificities or the maturation of memory B cell clones that produce broadly cross-reactive antibodies is unknown. Here, we longitudinally analyzed immune responses in healthy adults after two-dose vaccination with either a virus-like particle COVID-19 vaccine (CoVLP), CoVLP adjuvanted with AS03 (CoVLP+AS03), or a messenger RNA vaccination (mRNA-1273). CoVLP+AS03 enhanced the magnitude and durability of circulating antibodies and antigen-specific CD4 + T cell and memory B cell responses. Antigen-specific CD4 + T cells in the CoVLP+AS03 group at day 42 correlated with antigen-specific memory B cells at 6 months. CoVLP+AS03 induced memory B cell responses, which accumulated somatic hypermutations over 6 months, resulting in enhanced neutralization breadth of monoclonal antibodies. Furthermore, the fraction of broadly neutralizing antibodies encoded by memory B cells increased between day 42 and 6 months. These results indicate that AS03 enhances the antigenic breadth of B cell memory at the clonal level and induces progressive maturation of the B cell response.
Databáze: MEDLINE