Astragalus polysaccharide and aluminum adjuvant synergize to amplify immune responses induced by a recombinant COVID-19 vaccine

Despite extensive surveillance and intervention efforts, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a significant global public health threat. Vaccination is recognized as the most effective strategy for controlling SARS-CoV-2 infection. However, the immunogenicity of current COVID-19 vaccines, particularly protein subunit vaccines, requires further enhancement, highlighting the development of novel adjuvants to improve vaccine efficacy. In this study, we systematically evaluated the immunoenhancing effects of Astragalus polysaccharides (APS), a natural adjuvant, on SARS-CoV-2 recombinant protein vaccines using a BALB/c mouse immunization model. Our results demonstrate that APS significantly augments COVID-19 vaccine immunogenicity by promoting antibody production, activating antigen-specific IgG⁺ germinal center (GC) B cells and T follicular helper (Tfh) cells, and enhancing T cell-mediated immune responses. Transcriptomic sequencing analysis revealed that APS enhances immune responses through B cell-mediated mechanisms by upregulating pathways associated with antibody secretion and cellular immunity, thereby providing broad and long-lasting immune protection against SARS-CoV-2 and its variants. Notably, the combination of APS with aluminum adjuvant synergistically improved the immunogenicity of the SARS-CoV-2 recombinant protein vaccine without inducing systemic toxicity. These findings suggest that APS, as a potent immunomodulatory adjuvant for subunit protein-based vaccines, offers a promising strategy to address the limitations of current vaccine platforms.