{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T18:17:51Z","timestamp":1774981071152,"version":"3.50.1"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI114292"],"award-info":[{"award-number":["AI114292"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Plasmodium falciparum merozoite surface protein (PfMSP)2 is a target of parasite-neutralizing Abs. Inclusion of recombinant PfMSP2 (rPfMSP2) as a component of a multivalent malaria vaccine is of interest, but presents challenges. Previously, we used the highly immunogenic PfMSP8 as a carrier to enhance production and\/or immunogenicity of malaria vaccine targets. In this study, we exploited the benefits of rPfMSP8 as a carrier to optimize a rPfMSP2-based subunit vaccine. rPfMSP2 and chimeric rPfMSP2\/8 vaccines produced in Escherichia coli were evaluated in comparative immunogenicity studies in inbred (CB6F1\/J) and outbred (CD1) mice, varying the dose and adjuvant. Immunization of mice with both rPfMSP2-based vaccines elicited high-titer anti-PfMSP2 Abs that recognized the major allelic variants of PfMSP2. Vaccine-induced T cells recognized epitopes present in both PfMSP2 and the PfMSP8 carrier. Competition assays revealed differences in Ab specificities induced by the two rPfMSP2-based vaccines, with evidence of epitope masking by rPfMSP2-associated fibrils. In contrast to aluminum hydroxide (Alum) as adjuvant, formulation of rPfMSP2 vaccines with glucopyranosyl lipid adjuvant\u2013stable emulsion, a synthetic TLR4 agonist, elicited Th1-associated cytokines, shifting production of Abs to cytophilic IgG subclasses. The rPfMSP2\/8 + glucopyranosyl lipid adjuvant\u2013stable emulsion formulation induced significantly higher Ab titers with superior durability and capacity to opsonize P. falciparum merozoites for phagocytosis. Immunization with a trivalent vaccine including PfMSP2\/8, PfMSP1\/8, and the P. falciparum 25 kDa sexual stage antigen fused to PfMSP8 (Pfs25\/8) induced high levels of Abs specific for epitopes in each targeted domain, with no evidence of antigenic competition. These results are highly encouraging for the addition of rPfMSP2\/8 as a component of an efficacious, multivalent, multistage malaria vaccine.<\/jats:p>","DOI":"10.4049\/jimmunol.2000927","type":"journal-article","created":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T22:00:43Z","timestamp":1617228043000},"page":"1817-1831","source":"Crossref","is-referenced-by-count":6,"title":["Inclusion of an Optimized <i>Plasmodium falciparum<\/i> Merozoite Surface Protein 2\u2013Based Antigen in a Trivalent, Multistage Malaria Vaccine"],"prefix":"10.1093","volume":"206","author":[{"given":"Jacqueline S","family":"Eacret","sequence":"first","affiliation":[{"name":"Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine , Philadelphia, PA 19129"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth M","family":"Parzych","sequence":"additional","affiliation":[{"name":"Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine , Philadelphia, PA 19129"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donna M","family":"Gonzales","sequence":"additional","affiliation":[{"name":"Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine , Philadelphia, PA 19129"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"James M","family":"Burns","sequence":"additional","affiliation":[{"name":"Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine , Philadelphia, PA 19129"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,4,15]]},"reference":[{"key":"2025030417394581700_r1","volume-title":"World Malaria Report 2019.","author":"Ghehreyesus","year":"2019"},{"key":"2025030417394581700_r2","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0140-6736(15)60721-8","article-title":"Efficacy and safety of RTS,S\/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial. 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