{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:53:27Z","timestamp":1791075207664,"version":"4.1.0"},"reference-count":92,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T00:00:00Z","timestamp":1611878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/vaccines9020103","type":"journal-article","created":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T09:25:22Z","timestamp":1611912322000},"page":"103","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Orientation of Antigen Display on Self-Assembling Protein Nanoparticles Influences Immunogenicity"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5825-7640","authenticated-orcid":false,"given":"Cosette G.","family":"Schneider","sequence":"first","affiliation":[{"name":"Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"},{"name":"Oak Ridge Institute for Science and Education, Oak Ridge, TN 37831, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin A.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"},{"name":"Oak Ridge Institute for Science and Education, Oak Ridge, TN 37831, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Q.","family":"Sibilo","sequence":"additional","affiliation":[{"name":"Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"},{"name":"Parsons Corporation, Centreville, VA 20120, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4455-2432","authenticated-orcid":false,"given":"Kazutoyo","family":"Miura","sequence":"additional","affiliation":[{"name":"Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Rockville, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine L.","family":"Mallory","sequence":"additional","affiliation":[{"name":"Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"},{"name":"Parsons Corporation, Centreville, VA 20120, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Mann","sequence":"additional","affiliation":[{"name":"Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"},{"name":"Parsons Corporation, Centreville, VA 20120, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Karch","sequence":"additional","affiliation":[{"name":"Laboratory of Antigen and Adjuvants, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"},{"name":"Henry Jackson Foundation, Bethesda, MD 20817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoltan","family":"Beck","sequence":"additional","affiliation":[{"name":"Laboratory of Antigen and Adjuvants, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"},{"name":"Henry Jackson Foundation, Bethesda, MD 20817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2074-2373","authenticated-orcid":false,"given":"Gary R.","family":"Matyas","sequence":"additional","affiliation":[{"name":"Laboratory of Antigen and Adjuvants, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole A.","family":"Long","sequence":"additional","affiliation":[{"name":"Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Rockville, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8571-8956","authenticated-orcid":false,"given":"Elke","family":"Bergmann-Leitner","sequence":"additional","affiliation":[{"name":"Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Burkhard","sequence":"additional","affiliation":[{"name":"Alpha-O Peptides AG, 4125 Riehen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelina","family":"Angov","sequence":"additional","affiliation":[{"name":"Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,29]]},"reference":[{"key":"ref_1","unstructured":"WHO (2020). 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