Genetic linkage of autologous T cell epitopes in a chimeric recombinant construct improves anti-parasite and anti-disease protective effect of a malaria vaccine candidate.
We have reported the design of polyvalent synthetic and recombinant chimeras that include promiscuous T cell epitopes as a viable delivery system for pre-erythrocytic subunit malaria vaccines. To further assess the ability of several Plasmodium T cell epitopes to enhance vaccine potency, we designed a synthetic gene encoding four Plasmodium yoelii merozoite surface protein 1 (PyMSP1) CD4(+) promiscuous T cell epitopes fused in tandem to the homologous carboxyl terminal PyMSP1(19) fragment. This Recombinant Modular Chimera (PyRMC-MSP1(19)) was tested for immunogenicity and protective efficacy in comparative experiments with a recombinant protein expressing only the PyMSP1(19) fragment. Both proteins induced comparable antibody responses. However PyRMC-MSP1(19) elicited higher anti-parasite antibody titers and more robust protection against both hyper-parasitemia and malarial anemia. Most importantly, passive transfer of anti-PyRMC-MSP1(19), but not anti-PyMSP1(19) antibodies protected against heterologous challenge. These studies show that protective efficacy can be significantly improved by inclusion of an array of autologous promiscuous T cell epitopes in vaccine constructs.
Singh
Balwan
B
Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, United States.
Cabrera-Mora
Monica
M
Jiang
Jianlin
J
Galinski
Mary
M
Moreno
Alberto
A
D000595:Amino Acid Sequence; D000740:Anemia / Q000517:prevention & control; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D001483:Base Sequence; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D008288:Malaria / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology*; D008297:Male; D020066:Merozoite Surface Protein 1 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D018512:Parasitemia / Q000517:prevention & control; D010967:Plasmodium yoelii / Q000235:genetics / Q000276:immunology*; D022223:Vaccines, Subunit / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
D000913:Antibodies, Protozoan; D018984:Epitopes, T-Lymphocyte; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic