title: A chimeric Plasmodium falciparum merozoite surface protein vaccine induces high titers of parasite growth inhibitory antibodies.
abstract: The C-terminal 19-kDa domain of Plasmodium falciparum merozoite surface protein 1 (PfMSP119) is an established target of protective antibodies. However, clinical trials of PfMSP142, a leading blood-stage vaccine candidate which contains the protective epitopes of PfMSP119, revealed suboptimal immunogenicity and efficacy. Based on proof-of-concept studies in the Plasmodium yoelii murine model, we produced a chimeric vaccine antigen containing recombinant PfMSP119 (rPfMSP119) fused to the N terminus of P. falciparum merozoite surface protein 8 that lacked its low-complexity Asn/Asp-rich domain, rPfMSP8 (ΔAsn/Asp). Immunization of mice with the chimeric rPfMSP1/8 vaccine elicited strong T cell responses to conserved epitopes associated with the rPfMSP8 (ΔAsn/Asp) fusion partner. While specific for PfMSP8, this T cell response was adequate to provide help for the production of high titers of antibodies to both PfMSP119 and rPfMSP8 (ΔAsn/Asp) components. This occurred with formulations adjuvanted with either Quil A or with Montanide ISA 720 plus CpG oligodeoxynucleotide (ODN) and was observed in both inbred and outbred strains of mice. PfMSP1/8-induced antibodies were highly reactive with two major alleles of PfMSP119 (FVO and 3D7). Of particular interest, immunization with PfMSP1/8 elicited higher titers of PfMSP119-specific antibodies than a combined formulation of rPfMSP142 and rPfMSP8 (ΔAsn/Asp). As a measure of functionality, PfMSP1/8-specific rabbit IgG was shown to potently inhibit the in vitro growth of blood-stage parasites of the FVO and 3D7 strains of P. falciparum. These data support the further testing and evaluation of this chimeric PfMSP1/8 antigen as a component of a multivalent vaccine for P. falciparum malaria.
authors.affiliation: Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Alaro
authors.forename: Andrea
authors.initials: A
authors.lastname: Partridge
authors.forename: Kazutoyo
authors.initials: K
authors.lastname: Miura
authors.forename: Ababacar
authors.initials: A
authors.lastname: Diouf
authors.forename: Ana M
authors.initials: AM
authors.lastname: Lopez
authors.forename: Evelina
authors.initials: E
authors.lastname: Angov
authors.forename: Carole A
authors.initials: CA
authors.lastname: Long
authors.forename: James M
authors.initials: JM
authors.lastname: Burns
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D000939:Epitopes; D017780:Malaria Vaccines / Q000276:immunology*; D008297:Male; D020066:Merozoite Surface Protein 1 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D010963:Plasmodium falciparum / Q000276:immunology / Q000378:metabolism*; D010967:Plasmodium yoelii / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D000939:Epitopes; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D011994:Recombinant Proteins
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