Orientation of Antigen Display on Self-Assembling Protein Nanoparticles Influences Immunogenicity

oleh: Cosette G. Schneider, Justin A. Taylor, Michael Q. Sibilo, Kazutoyo Miura, Katherine L. Mallory, Christopher Mann, Christopher Karch, Zoltan Beck, Gary R. Matyas, Carole A. Long, Elke Bergmann-Leitner, Peter Burkhard, Evelina Angov

Format: Article
Diterbitkan: MDPI AG 2021-01-01

Deskripsi

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 <i>P. falciparum</i> (<i>Pf</i>) merozoite surface protein 1 subunit, PfMSP1<sub>19</sub>, and <i>Pf</i> 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.