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

• Published in: Vaccines (Basel) Vol. 9; no. 2; p. 103
• Main Authors: Schneider, Cosette G, Taylor, Justin A, Sibilo, Michael Q, Miura, Kazutoyo, Mallory, Katherine L, Mann, Christopher, Karch, Christopher, Beck, Zoltan, Matyas, Gary R, Long, Carole A, Bergmann-Leitner, Elke, Burkhard, Peter, Angov, Evelina
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29-01-2021; MDPI
• Subjects: Amino acids; Antibodies; Antigen presentation; Antigens; Autoantigens; Cloning; display; E coli; Epitopes; Folding; Immune response; Immune system; Immunogenicity; Malaria; Merozoite surface protein 1; multi-stage; Nanoparticles; Parasites; PfCelTOS; PfMSP119; Proteins; Rabbits; self-assembling protein nanoparticles; Self-assembly; Sporozoites; vaccine; Vaccines; Zygotes; United States > US; Chicago Illinois; PfMSP119; multi-stage; self-assembling protein nanoparticles; vaccine; PfCelTOS; display
• ISSN: 2076-393X; 2076-393X
• DOI: 10.3390/vaccines9020103

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
(
) merozoite surface protein 1 subunit, PfMSP1
, and
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.