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- Title
AS03 adjuvant enhances the magnitude, persistence, and clonal breadth of memory B cell responses to a plant-based COVID-19 vaccine in humans.
- Authors
Grigoryan, Lilit; Feng, Yupeng; Bellusci, Lorenza; Lai, Lilin; Wali, Bushra; Ellis, Madison; Yuan, Meng; Arunachalam, Prabhu S.; Hu, Mengyun; Kowli, Sangeeta; Gupta, Sheena; Maysel-Auslender, Sofia; Maecker, Holden T.; Samaha, Hady; Rouphael, Nadine; Wilson, Ian A.; Moreno, Alberto C.; Suthar, Mehul S.; Khurana, Surender; Pillet, Stéphane
- Abstract
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. Editor's summary: Adjuvants are known to improve the magnitude, durability, and breadth of the immune response to vaccination, but how they modulate memory B cells is unclear. Grigoryan et al. analyzed immune responses in healthy individuals at multiple time points after two-dose vaccination with a plant-based SARS-CoV-2 vaccine (CoVLP) with or without adjuvant (AS03). AS03 adjuvant induced robust and more persistent RBD-specific memory B cells with increased neutralization breadth. This was due to AS03 promoting the selection of broadly neutralizing memory B cells, which accumulated SHMs over time. These findings highlight the role of adjuvants in enhancing memory B cell responses to vaccination. —Hannah Isles
- Subjects
IMMUNOLOGIC memory; COVID-19 pandemic; COVID-19 vaccines; VIRUS-like particles; MESSENGER RNA
- Publication
Science Immunology, 2024, Vol 9, Issue 94, p1
- ISSN
2470-9468
- Publication type
Article
- DOI
10.1126/sciimmunol.adi8039