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 Karch; Zoltan Beck; Gary R Matyas; Carole A Long; Elke Bergmann-Leitner; Peter Burkhard; Evelina Angov

doi:10.3390/vaccines9020103

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

Vaccines (Basel). 2021 Jan 29;9(2):103. doi: 10.3390/vaccines9020103.

Authors

Cosette G Schneider^{1

2}, Justin A Taylor^{1

2}, Michael Q Sibilo^{1

3}, Kazutoyo Miura⁴, Katherine L Mallory^{1

3}, Christopher Mann^{1

3}, Christopher Karch^{5

6}, Zoltan Beck^{5

6}, Gary R Matyas⁵, Carole A Long⁴, Elke Bergmann-Leitner¹, Peter Burkhard⁷, Evelina Angov¹

Affiliations

¹ Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
² Oak Ridge Institute for Science and Education, Oak Ridge, TN 37831, USA.
³ Parsons Corporation, Centreville, VA 20120, USA.
⁴ Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Rockville, MD 20892, USA.
⁵ Laboratory of Antigen and Adjuvants, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
⁶ Henry Jackson Foundation, Bethesda, MD 20817, USA.
⁷ Alpha-O Peptides AG, 4125 Riehen, Switzerland.

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.

Keywords: PfCelTOS; PfMSP119; display; multi-stage; self-assembling protein nanoparticles; vaccine.