Shift in epitope dominance of IgM and IgG responses to Plasmodium falciparum MSP1 block 4

<p>Abstract</p> <p>Background</p> <p><it>Plasmodium falciparum </it>merozoite surface protein-1 (MSP1) has been extensively studied as a blood-stage malaria vaccine candidate, with most work focused on the conserved 19 kDa and semi-conserved 42 kDa C-terminal regions (blocks 16-17) and the hypervariable N-terminal repeat region (block 2). However, recent genotyping studies suggest that additional regions of MSP1 may be under selective pressure, including a locus of intragenic recombination designated as block 4 within the 3' region of the gene.</p> <p>Methods</p> <p>The current study examined the antibody response to the two parental and two recombinant forms of block 4 and to blocks 16-17 (3D7) in study populations from Colombia, Papua New Guinea and Cameroon that differ in malaria transmission intensity and ethnic composition.</p> <p>Results</p> <p>IgM and IgG antibodies were detected against parental and recombinant MSP1 block 4 peptides in all three populations. Overall, 32-44% of the individuals produced IgM to one or more of the peptides, with most individuals having IgM antibodies reactive with both parental and recombinant forms. In contrast, IgG seropositivity to block 4 varied among populations (range 15-65%), with the majority of antibodies showing specificity for one or a pair of block 4 peptides. The IgG response to block 4 was significantly lower than that to blocks 16-17, indicating block 4 is subdominant. Antibodies to block 4 and blocks 16-17 displayed distinct IgG subclass biases, with block 4 responses biased toward IgG3 and blocks 16-17 toward IgG1. These patterns of responsiveness were consistently observed in the three study populations.</p> <p>Conclusions</p> <p>Production of antibodies specific for each parental and recombinant MSP1 block 4 allele in different populations exposed to <it>P. falciparum </it>is consistent with balancing selection of the MSP1 block 4 region by the immune response of individuals in areas of both low and high malaria transmission. MSP1 block 4 determinants may be important in isolate-specific immunity to <it>P. falciparum</it>.</p

Study of the antigenicity of P. yoelii parasitized erythrocyte ghost antigens and their role in protection

Thesis (Ph. D.)--University of Hawaii at Manoa, 1990.Includes bibliographical references (leaves 134-152)Microfiche.xvi, 152 leaves, bound ill. 29 cmThe overall objective of this dissertation was the study of membrane antigens of parasitized erythrocytes in Plasmodium yoelii, a rodent malaria model. Unstimulated peritoneal cells from C57/Bl 10 mice phagocytosed P. yoelii parasitized erythrocytes in vitro more effectively in the presence of immune and hyperimmune sera than normal sera, suggesting these antibodies react with novel antigens expressed in the membrane of parasitized erythrocytes. A surface immunofluorescence assay used to detect the binding of hyperimmune serum antibodies to surface antigens was suggestive of, but did not conclusively demonstrate, the presence of novel surface antigens on parasitized erythrocytes. It was not possible to measure specific anti-plasmodial antibody using an enzyme linked immonosorbent assay (ELISA) although different variations of the technique were pursued. There was no significant difference between the binding of normal or hyperimmune sera to normal erythrocyte ghosts or R. yoelii parasitized erythrocyte ghosts in the ELISA. More conclusive evidence for the presence of parasite-derived membrane antigens in infected erythrocytes were obtained by 50S-polyacrylamide gel electrophoresis, immunoblotting and immunoprecipitation of biosynthetically labeled membrane antigens. Plasma membranes of P. yoelii trophozoites contained ten neoproteins with apparent molecular masses of 92.5, 79, 76, 69, 60, 43, 31, 30, 19 and 14.3 kDa. These proteins were metabolically labeled with 3H Isoleucine and immunoprecipitated by hyperimmune serum, however not all of these proteins were detected by immunoblotting. Some of these proteins appeared to have co-migrating normal host membrane antigens (92.5, 80 and 69 kDa). A vaccination experiment was performed to determine whether parasitized membrane preparations could induce an immune response capable of protecting mice against P. yoelii infection. BALB/c mice immunized intravenously with a single dose of P. yoelii parasitized erythrocyte ghosts without adjuvant developed a significant level of protective immunity against challenge with the homologous parasite as compared to controls, immunized with normal erythrocyte ghosts. In contrast, mice vaccinated with either two doses of normal erythrocyte ghosts or P. yoelii parasitized erythrocyte ghosts with Complete Freund's Adjuvant injected subcutaneously into the tail were not protected against challenge with P. yoelii parasites. The results of this study support a possible role of parasitized erythrocyte membrane antigens in immunity to malaria in the P. yoelii mouse malaria model