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

Sci Immunol. 2024 Apr 5;9(94):eadi8039. doi: 10.1126/sciimmunol.adi8039. Epub 2024 Apr 5.


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.

MeSH terms

  • Adult
  • Antibodies, Viral
  • COVID-19 Vaccines
  • COVID-19* / prevention & control
  • Drug Combinations
  • Humans
  • Influenza Vaccines*
  • Influenza, Human*
  • Memory B Cells
  • Polysorbates*
  • Squalene*
  • alpha-Tocopherol*


  • AS03 adjuvant
  • Influenza Vaccines
  • COVID-19 Vaccines
  • Antibodies, Viral
  • Drug Combinations
  • Polysorbates
  • Squalene
  • alpha-Tocopherol