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Protective immune responses elicited by immunization with a chimeric blood-stage malaria vaccine persist but are not boosted by Plasmodium yoelii challenge infection
Journal article   Open access   Peer reviewed

Protective immune responses elicited by immunization with a chimeric blood-stage malaria vaccine persist but are not boosted by Plasmodium yoelii challenge infection

James R Alaro, Michele M Lynch and James M Burns, Jr
Vaccine, v 28(42), pp 6876-6884
04 Oct 2010
PMID: 20709001
url
https://doi.org/10.1016/j.vaccine.2010.08.018View
Published, Version of Record (VoR) Open

Abstract

Recombinant Fusion Proteins - immunology Antigens, Protozoan - immunology Cell Proliferation Malaria - immunology Male Epitopes, B-Lymphocyte - immunology Plasmodium yoelii - immunology Malaria - prevention & control Antibodies, Protozoan - blood Animals B-Lymphocytes - immunology Merozoite Surface Protein 1 - immunology Malaria Vaccines - immunology Antibody Formation T-Lymphocytes - immunology Mice Mice, Inbred BALB C Protozoan Proteins - immunology
An efficacious malaria vaccine remains elusive despite concerted efforts. Using the Plasmodium yoelii murine model, we previously reported that immunization with the C-terminal 19 kDa domain of merozoite surface protein 1 (MSP1(19)) fused to full-length MSP8 protected against lethal P. yoelii 17XL, well beyond that achieved by single or combined immunizations with the component antigens. Here, we continue the evaluation of the chimeric PyMSP1/8 vaccine. We show that immunization with rPyMSP1/8 vaccine elicited an MSP8-restricted T cell response that was sufficient to provide help for both PyMSP1(19) and PyMSP8-specific B cells to produce high and sustained levels of protective antibodies. The enhanced efficacy of immunization with rPyMSP1/8, in comparison to a combined formulation of rPyMSP1(42) and rPyMSP8, was not due to improved conformation of protective B cell epitopes in the chimeric molecule. Unexpectedly, rPyMSP1/8 vaccine-induced antibody responses were not boosted by exposure to P. yoelii 17XL infected RBCs. However, rPyMSP1/8 immunized and infected mice mounted robust responses to a diverse set of blood-stage antigens. The data support the further development of an MSP1/8 chimeric vaccine but also suggest that vaccines that prime for responses to a diverse set of parasite proteins will be required to maximize vaccine efficacy.

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Web of Science research areas
Immunology
Medicine, Research & Experimental
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