Systems Serology-Based Comparison of Humoral Immune Responses Induced by Liposome or Aluminum Hydroxide Adjuvanted SARS-CoV-2 Spike Protein

Adjuvants play a crucial role in enhancing vaccine-induced immune responses by shaping the magnitude and quality of humoral and cellular immunity. However, the mechanism through which different adjuvants modulate effector functions is not fully understood. Here, we developed an International Vaccine Institute liposome-based adjuvant (ILA) and comprehensively compared humoral immune profiles in mice following the administration of SARS-CoV-2 spike (S) protein formulated with either ILA or aluminum hydroxide (alum) using a systems serology approach. No significant differences were observed in antigen-specific total IgG and neutralizing antibody titers between the two adjuvanted groups. However, the ILA group demonstrated a broader spectrum of humoral immune responses, exhibiting higher levels of antigen-specific IgG2a, IgG2b, and IgG3 compared to the alum group. In addition, S-specific antibody binding to Fcγ receptor (FcγR) 1 and FcγR4 was significantly higher in the ILA group compared to alum. Moreover, Fc-mediated effector functions, such as antibody-mediated monocyte and neutrophil phagocytosis, were significantly more active in the ILA-adjuvanted group. Overall, these findings demonstrate that ILA induces antibodies with superior FcγR binding and Fc-mediated effector functions compared to alum, highlighting its potential role in improving vaccine-induced immunity.