title: Immunological Cross-Reactivity between Malaria Vaccine Target Antigen P48/45 in Plasmodium vivax and P. falciparum and Cross-Boosting of Immune Responses.
abstract: In general, malaria immunity has been suggested to be species specific with very little, if any, known cross-reactivity between Plasmodium vivax and P. falciparum, both of which are responsible for >90% of human malaria, and co-endemic in many countries. It is therefore believed that species-specific immunity may be needed to target different species of Plasmodium. Pfs48/45 and Pvs48/45 are well established targets in the sexual stages of the malaria parasites, and are being pursued for the development of transmission blocking vaccines. Comparison of their sequences reveals 61% and 55% identity at the DNA and protein level, respectively raising the possibility that these two target antigens might share cross-reacting epitopes. Having succeeded in expressing recombinant Pfs48/45 and Pvs48/45 proteins, we hypothesized that these proteins will not only exhibit immunological cross-reactivity but also cross-boost immune responses. Mice were immunized with purified recombinant proteins using CFA, Montanide ISA-51 and alum as adjuvants, and the sera were analyzed by ELISA, Western blotting and indirect fixed and live IFA to address the hypothesis. Our studies revealed that Pvs48/45-immune sera showed strong cross-reactivity to full length Pfs48/45 protein, and the majority of this cross reactivity was in the amino-terminal and carboxyl-terminal sub-fragments of Pfs48/45. In cross-boosting experiments Pfs48/45 and Pvs48/45 antigens were able to cross-boost each other in mouse immunization studies. Additionally we also noticed an effect of adjuvants in the overall magnitude of observed cross-reactivity. These studies may have significant implications for immunity targeting transmission of both the species of malaria parasites.
authors.affiliation: Department of Tropical Medicine, School of Public Health and Tropical Medicine, and Vector-Borne Infectious Disease Research Center, Tulane University, New Orleans, Louisiana, 70112, United States of America.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Tropical Medicine, School of Public Health and Tropical Medicine, and Vector-Borne Infectious Disease Research Center, Tulane University, New Orleans, Louisiana, 70112, United States of America.
authors.forename: Geetha P
authors.initials: GP
authors.lastname: Bansal
authors.affiliation: Department of Tropical Medicine, School of Public Health and Tropical Medicine, and Vector-Borne Infectious Disease Research Center, Tulane University, New Orleans, Louisiana, 70112, United States of America.
authors.forename: Kristen
authors.initials: K
authors.lastname: Merino
authors.affiliation: Department of Tropical Medicine, School of Public Health and Tropical Medicine, and Vector-Borne Infectious Disease Research Center, Tulane University, New Orleans, Louisiana, 70112, United States of America.
authors.forename: Nirbhay
authors.initials: N
authors.lastname: Kumar
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007110:Immunity, Active / Q000187:drug effects; D017780:Malaria Vaccines / Q000276:immunology* / Q000627:therapeutic use; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000276:immunology; D016780:Malaria, Vivax / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D010963:Plasmodium falciparum / Q000276:immunology / Q000472:pathogenicity; D010966:Plasmodium vivax / Q000276:immunology / Q000472:pathogenicity
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000939:Epitopes; D017780:Malaria Vaccines