Inclusion of an Optimized Plasmodium falciparum Merozoite Surface Protein 2-Based Antigen in a Trivalent, Multistage Malaria Vaccine.

Autor:	Eacret JS; Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129., Parzych EM; Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129., Gonzales DM; Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129., Burns JM Jr; Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129 jmb53@drexel.edu.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2021 Apr 15; Vol. 206 (8), pp. 1817-1831. Date of Electronic Publication: 2021 Mar 31.
DOI:	10.4049/jimmunol.2000927
Abstrakt:	Plasmodium falciparum merozoite surface protein ( Pf MSP)2 is a target of parasite-neutralizing Abs. Inclusion of recombinant Pf MSP2 (r Pf MSP2) as a component of a multivalent malaria vaccine is of interest, but presents challenges. Previously, we used the highly immunogenic Pf MSP8 as a carrier to enhance production and/or immunogenicity of malaria vaccine targets. In this study, we exploited the benefits of r Pf MSP8 as a carrier to optimize a r Pf MSP2-based subunit vaccine. r Pf MSP2 and chimeric r Pf MSP2/8 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 r Pf MSP2-based vaccines elicited high-titer anti- Pf MSP2 Abs that recognized the major allelic variants of Pf MSP2. Vaccine-induced T cells recognized epitopes present in both Pf MSP2 and the Pf MSP8 carrier. Competition assays revealed differences in Ab specificities induced by the two r Pf MSP2-based vaccines, with evidence of epitope masking by r Pf MSP2-associated fibrils. In contrast to aluminum hydroxide (Alum) as adjuvant, formulation of r Pf 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 Pf MSP2/8 + glucopyranosyl lipid adjuvant-stable 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 Pf MSP2/8, Pf MSP1/8, and the P. falciparum 25 kDa sexual stage antigen fused to Pf MSP8 ( Pf 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 Pf MSP2/8 as a component of an efficacious, multivalent, multistage malaria vaccine. (Copyright © 2021 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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