Orientation of Antigen Display on Self-Assembling Protein Nanoparticles Influences Immunogenicity
Cosette G. Schneider, Justin A. Taylor, Michael Q. Sibilo, Kazutoyo Miura, Katherine L. Mallory, Christopher Mann, Christopher P. Karch, Zoltán Beck, Gary R. Matyas, Carole A. Long, Elke S. Bergmann‐Leitner, Peter Burkhard, Evelina Angov
Abstract
Self-assembling protein nanoparticles (SAPN) serve as a repetitive antigen delivery platform with high-density epitope display; however, antigen characteristics such as size and epitope presentation can influence the immunogenicity of the assembled particle and are aspects to consider for a rationally designed effective vaccine. Here, we characterize the folding and immunogenicity of heterogeneous antigen display by integrating (a) dual-stage antigen SAPN presenting the P. falciparum (Pf) merozoite surface protein 1 subunit, PfMSP119, and Pf cell-traversal protein for ookinetes and sporozoites, PfCelTOS, in addition to (b) a homogenous antigen SAPN displaying two copies of PfCelTOS. Mice and rabbits were utilized to evaluate antigen-specific humoral and cellular induction as well as functional antibodies via growth inhibition of the blood-stage parasite. We demonstrate that antigen orientation and folding influence the elicited immune response, and when appropriately designed, SAPN can serve as an adaptable platform for an effective multi-antigen display.