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

Autor: 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
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Vaccines, Vol 9, Iss 2, p 103 (2021)
Druh dokumentu: article
ISSN: 2076-393X
DOI: 10.3390/vaccines9020103
Popis: 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.
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