Logo image
Back
Inclusion of an Optimized Plasmodium falciparum Merozoite Surface Protein 2-Based Antigen in a Trivalent, Multistage Malaria Vaccine
Journal article   Open access   Peer reviewed

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

Jacqueline S Eacret, Elizabeth M Parzych, Donna M Gonzales and James M Burns, Jr
The Journal of immunology (1950), v 206(8), pp 1817-1831
15 Apr 2021
DOI: https://doi.org/10.4049/jimmunol.2000927
PMID: 33789984
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.4049/jimmunol.2000927View
Accepted (AM)Open Access (License Unspecified),  Open

Abstract

Animals Antibodies, Neutralizing - metabolism Antibodies, Protozoan - metabolism Antigens, Protozoan - genetics Antigens, Protozoan - immunology Epitope Mapping Female Glucosides Immunodominant Epitopes Immunoglobulin G - metabolism Lipid A Malaria - immunology Malaria Vaccines - genetics Malaria Vaccines - immunology Male Merozoites - immunology Merozoites - metabolism Mice Mice, Inbred BALB C Mice, Inbred C57BL Phagocytosis Plasmodium falciparum - immunology Protozoan Proteins - genetics Protozoan Proteins - immunology Th1 Cells - immunology
merozoite surface protein ( MSP)2 is a target of parasite-neutralizing Abs. Inclusion of recombinant MSP2 (r MSP2) as a component of a multivalent malaria vaccine is of interest, but presents challenges. Previously, we used the highly immunogenic MSP8 as a carrier to enhance production and/or immunogenicity of malaria vaccine targets. In this study, we exploited the benefits of r MSP8 as a carrier to optimize a r MSP2-based subunit vaccine. r MSP2 and chimeric r MSP2/8 vaccines produced in 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 MSP2-based vaccines elicited high-titer anti- MSP2 Abs that recognized the major allelic variants of MSP2. Vaccine-induced T cells recognized epitopes present in both MSP2 and the MSP8 carrier. Competition assays revealed differences in Ab specificities induced by the two r MSP2-based vaccines, with evidence of epitope masking by r MSP2-associated fibrils. In contrast to aluminum hydroxide (Alum) as adjuvant, formulation of r 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 MSP2/8 + glucopyranosyl lipid adjuvant-stable emulsion formulation induced significantly higher Ab titers with superior durability and capacity to opsonize merozoites for phagocytosis. Immunization with a trivalent vaccine including MSP2/8, MSP1/8, and the 25 kDa sexual stage antigen fused to MSP8 ( 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 MSP2/8 as a component of an efficacious, multivalent, multistage malaria vaccine.

Metrics

16 Record Views
4 citations in Web of Science
3 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Web of Science research areas
Immunology
Logo image