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Immunization with merozoite surface protein 2 fused to a Plasmodium-specific carrier protein elicits strain-specific and strain-transcending, opsonizing antibody
Journal article   Open access   Peer reviewed

Immunization with merozoite surface protein 2 fused to a Plasmodium-specific carrier protein elicits strain-specific and strain-transcending, opsonizing antibody

Jacqueline S Eacret, Donna M Gonzales, Raymond G Franks and James M Burns, Jr
Scientific reports, v 9(1), pp 9022-17
21 Jun 2019
DOI: https://doi.org/10.1038/s41598-019-45440-4
PMID: 31227760
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1038/s41598-019-45440-4View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

Animals Antibodies, Protozoan - immunology Antibody Specificity - immunology Antigens, Protozoan - chemistry Antigens, Protozoan - immunology Humans Malaria Vaccines - administration & dosage Malaria Vaccines - chemistry Malaria Vaccines - immunology Malaria, Falciparum - immunology Malaria, Falciparum - prevention & control Merozoites - immunology Opsonin Proteins - immunology Phagocytosis - immunology Protozoan Proteins - chemistry Protozoan Proteins - immunology Rabbits Species Specificity THP-1 Cells Vaccination - methods
Vaccine trials and cohort studies in Plasmodium falciparum endemic areas indicate that naturally-acquired and vaccine-induced antibodies to merozoite surface protein 2 (MSP2) are associated with resistance to malaria. These data indicate that PfMSP2 has significant potential as a component of a multi-antigen malaria vaccine. To overcome challenges encountered with subunit malaria vaccines, we established that the use of highly immunogenic rPfMSP8 as a carrier protein for leading vaccine candidates rPfMSP1 and rPfs25 facilitated antigen production, minimized antigenic competition and enhanced induction of functional antibodies. We applied this strategy to optimize a rPfMSP2 (3D7)-based subunit vaccine by producing unfused rPfMSP2 or chimeric rPfMSP2/8 in Escherichia coli. rPfMSP2 formed fibrils, which induced splenocyte proliferation in an antigen receptor-independent, TLR2-dependent manner. However, fusion to rPfMSP8 prevented rPfMSP2 amyloid-like fibril formation. Immunization of rabbits elicited high-titer anti-PfMSP2 antibodies that recognized rPfMSP2 of the 3D7 and FC27 alleles, as well as native PfMSP2. Competition assays revealed a difference in the specificity of antibodies induced by the two rPfMSP2-based vaccines, with evidence of epitope masking by rPfMSP2-associated fibrils. Rabbit anti-PfMSP2/8 was superior to rPfMSP2-elicited antibody at opsonizing P. falciparum merozoites for phagocytosis. These data establish rPfMSP8 as an effective carrier for a PfMSP2-based subunit malaria vaccine.

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Web of Science research areas
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