{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Eacret JS"],"funding":["NIAID NIH HHS"],"pagination":["1817-1831"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8026686"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["206(8)"],"pubmed_abstract":["<i>Plasmodium falciparum</i> merozoite surface protein (<i>Pf</i>MSP)2 is a target of parasite-neutralizing Abs. Inclusion of recombinant <i>Pf</i>MSP2 (r<i>Pf</i>MSP2) as a component of a multivalent malaria vaccine is of interest, but presents challenges. Previously, we used the highly immunogenic <i>Pf</i>MSP8 as a carrier to enhance production and/or immunogenicity of malaria vaccine targets. In this study, we exploited the benefits of r<i>Pf</i>MSP8 as a carrier to optimize a r<i>Pf</i>MSP2-based subunit vaccine. r<i>Pf</i>MSP2 and chimeric r<i>Pf</i>MSP2/8 vaccines produced in <i>Escherichia coli</i> were evaluated in comparative immunogenicity studies in inbred (CB6F1/J) and outbred (CD1) mice, varying the dose and adjuvant. Immunization of mice with both r<i>Pf</i>MSP2-based vaccines elicited high-titer anti-<i>Pf</i>MSP2 Abs that recognized the major allelic variants of <i>Pf</i>MSP2. Vaccine-induced T cells recognized epitopes present in both <i>Pf</i>MSP2 and the <i>Pf</i>MSP8 carrier. Competition assays revealed differences in Ab specificities induced by the two r<i>Pf</i>MSP2-based vaccines, with evidence of epitope masking by r<i>Pf</i>MSP2-associated fibrils. In contrast to aluminum hydroxide (Alum) as adjuvant, formulation of r<i>Pf</i>MSP2 vaccines with glucopyranosyl lipid adjuvant-stable emulsion, a synthetic TLR4 agonist, elicited Th1-associated cytokines, shifting production of Abs to cytophilic IgG subclasses. The r<i>Pf</i>MSP2/8 + glucopyranosyl lipid adjuvant-stable emulsion formulation induced significantly higher Ab titers with superior durability and capacity to opsonize <i>P. falciparum</i> merozoites for phagocytosis. Immunization with a trivalent vaccine including <i>Pf</i>MSP2/8, <i>Pf</i>MSP1/8, and the <i>P. falciparum</i> 25 kDa sexual stage antigen fused to <i>Pf</i>MSP8 (<i>Pf</i>s25/8) 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 r<i>Pf</i>MSP2/8 as a component of an efficacious, multivalent, multistage malaria vaccine."],"journal":["Journal of immunology (Baltimore, Md. : 1950)"],"pubmed_title":["Inclusion of an Optimized <i>Plasmodium falciparum</i> Merozoite Surface Protein 2-Based Antigen in a Trivalent, Multistage Malaria Vaccine."],"pmcid":["PMC8026686"],"funding_grant_id":["R01 AI114292"],"pubmed_authors":["Gonzales DM","Eacret JS","Burns JM","Parzych EM"],"additional_accession":[]},"is_claimable":false,"name":"Inclusion of an Optimized <i>Plasmodium falciparum</i> Merozoite Surface Protein 2-Based Antigen in a Trivalent, Multistage Malaria Vaccine.","description":"<i>Plasmodium falciparum</i> merozoite surface protein (<i>Pf</i>MSP)2 is a target of parasite-neutralizing Abs. Inclusion of recombinant <i>Pf</i>MSP2 (r<i>Pf</i>MSP2) as a component of a multivalent malaria vaccine is of interest, but presents challenges. Previously, we used the highly immunogenic <i>Pf</i>MSP8 as a carrier to enhance production and/or immunogenicity of malaria vaccine targets. In this study, we exploited the benefits of r<i>Pf</i>MSP8 as a carrier to optimize a r<i>Pf</i>MSP2-based subunit vaccine. r<i>Pf</i>MSP2 and chimeric r<i>Pf</i>MSP2/8 vaccines produced in <i>Escherichia coli</i> were evaluated in comparative immunogenicity studies in inbred (CB6F1/J) and outbred (CD1) mice, varying the dose and adjuvant. Immunization of mice with both r<i>Pf</i>MSP2-based vaccines elicited high-titer anti-<i>Pf</i>MSP2 Abs that recognized the major allelic variants of <i>Pf</i>MSP2. Vaccine-induced T cells recognized epitopes present in both <i>Pf</i>MSP2 and the <i>Pf</i>MSP8 carrier. Competition assays revealed differences in Ab specificities induced by the two r<i>Pf</i>MSP2-based vaccines, with evidence of epitope masking by r<i>Pf</i>MSP2-associated fibrils. In contrast to aluminum hydroxide (Alum) as adjuvant, formulation of r<i>Pf</i>MSP2 vaccines with glucopyranosyl lipid adjuvant-stable emulsion, a synthetic TLR4 agonist, elicited Th1-associated cytokines, shifting production of Abs to cytophilic IgG subclasses. The r<i>Pf</i>MSP2/8 + glucopyranosyl lipid adjuvant-stable emulsion formulation induced significantly higher Ab titers with superior durability and capacity to opsonize <i>P. falciparum</i> merozoites for phagocytosis. Immunization with a trivalent vaccine including <i>Pf</i>MSP2/8, <i>Pf</i>MSP1/8, and the <i>P. falciparum</i> 25 kDa sexual stage antigen fused to <i>Pf</i>MSP8 (<i>Pf</i>s25/8) 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 r<i>Pf</i>MSP2/8 as a component of an efficacious, multivalent, multistage malaria vaccine.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Apr","modification":"2025-04-29T11:34:24.424Z","creation":"2025-04-06T19:54:44.311Z"},"accession":"S-EPMC8026686","cross_references":{"pubmed":["33789984"],"doi":["10.4049/jimmunol.2000927"]}}