Antigen avidity drives the durability of the vaccine immune response 4389

Abstract Description A key challenge in vaccine development is designing immunogens that provide durable protection. While antigen avidity is believed to play a critical role in eliciting robust B cell responses, its effects are not well understood partly due to confounding factors such as differences in antigen size and T cell help. We hypothesized that antigen avidity is essential for regulating the magnitude and longevity of germinal center (GC) B cells, memory B cells (MBCs), and long-lived plasma cells (LLPCs) post-vaccination. To test this, we utilized multiple preclinical HIV vaccine B cell transfer models paired with a mosaic nanoparticle-based immunogen platform that allows precise variation of antigen avidity (0–60 copies) on particles of uniform size with conserved T cell helper epitopes. GC seeding and outgrowth of VRC01gHL B cells correlated with decreasing antigen avidity. High-avidity immunogens promoted durability of VRC01gHL GC responses that lasted up to six months post-prime. Moreover, VRC01gHL MBC and LLPC formation and durability tracked with antigen avidity. In a model of reduced interclonal competition, VRC01gHL GC responses and memory responses to low-avidity particles were rescued. Finally, in two additional models using authentic human germline (HuGL) VRC01-class B cells, antigen avidity was critical in both GC B cell competition and MBC formation. Together, these results underscore the critical role of antigen avidity in shaping durable vaccine immune responses. Funding Sources Supported by NIH 5DP2AI154410-03; NIH 5R00AI145762-04; UTMB Startup Fund, James W. McLaughlin Fellowship Fund. Topic Categories Vaccines and Immunotherapy (VAC)