Orientation of Antigen Display on Self-Assembling Protein Nanoparticles Influences Immunogenicity
Open Access
- 29 January 2021
- Vol. 9 (2), 103
- https://doi.org/10.3390/vaccines9020103
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.This publication has 92 references indexed in Scilit:
- Conformation‐specific Display of 4E10 and 2F5 Epitopes on Self‐assembling Protein Nanoparticles as a Potential HIV VaccineChemical Biology & Drug Design, 2012
- A Novel Vaccine Using Nanoparticle Platform to Present Immunogenic M2e against Avian Influenza InfectionInfluenza Research and Treatment, 2011
- Multiple Antigen Peptide Vaccines againstPlasmodium falciparumMalariaInfection and Immunity, 2010
- Structure of the Plasmodium falciparum Circumsporozoite Protein, a Leading Malaria Vaccine CandidateOnline Journal of Public Health Informatics, 2009
- MSP-1p42-specific antibodies affect growth and development of intra-erythrocytic parasites of Plasmodium falciparumMalaria Journal, 2009
- Randomized, Double‐Blind, Phase 2a Trial of Falciparum Malaria Vaccines RTS,S/AS01B and RTS,S/AS02A in Malaria‐Naive Adults: Safety, Efficacy, and Immunologic Associates of ProtectionThe Journal of Infectious Diseases, 2009
- Peptide Nanoparticles as Novel Immunogens: Design and Analysis of a Prototypic Severe Acute Respiratory Syndrome VaccineChemical Biology & Drug Design, 2008
- Long-Lasting Protective Immune Response to the 19-Kilodalton Carboxy-Terminal Fragment ofPlasmodium yoeliiMerozoite Surface Protein 1 in MiceClinical and Vaccine Immunology, 2007
- Immunity to RecombinantPlasmodium falciparumMerozoite Surface Protein 1 (MSP1): Protection inAotus nancymaiMonkeys Strongly Correlates with Anti-MSP1 Antibody Titer and In Vitro Parasite-Inhibitory ActivityInfection and Immunity, 2006
- The layered fold of the TSR domain of P. falciparum TRAP contains a heparin binding siteProtein Science, 2006