Comparison of the immunogenic properties of recombinant proteins representing the Plasmodium vivax vaccine candidate MSP1(19) expressed in distinct bacterial vectors.
The 19kDa C-terminal region of the merozoite surface protein 1 (MSP1(19)) is one of the most promising vaccine candidates against the erythrocytic forms of malaria. In the present study, we used three different Escherichia coli expression vectors to generate five recombinant proteins representing the MSP1(19) of Plasmodium vivax. These proteins were compared for reactivity with a panel of sera from individuals naturally exposed to P. vivax and for their immunogenicity in mice. Among the proteins studied, MSP1(19) expressed by the vector pET (His(6)-MSP1(19)) was better recognized by the antibodies of several individuals exposed to P. vivax. The addition of the T-cell Pan-allelic DR epitope (PADRE) did not alter the recognition of this recombinant protein by human antibodies. Although recombinant proteins were immunogenic to mice, immunization with MSP1(19) expressed by the pET or pGEX vectors induced significantly higher antibody titers than a protein produced by the pMAL vector. The antibody immune response elicited by His(6)-MSP1(19) containing the PADRE epitope was compared using different adjuvant formulations. After only two immunizing doses, antibody titers induced in the presence of the adjuvants TiterMax, MPL/TDM/CWS or alum plus CpG ODN 1826 were as high as titers generated by complete Freund's adjuvant. We concluded that, among the bacterial recombinant proteins, MSP1(19) expressed by the vector pET should be selected for further evaluation in pre-clinical immunizations against P. vivax.
Cunha
M G
MG
Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina, Rua Botucatu 862, 6th Floor, São Paulo 04023-062, SP, Brazil.
Rodrigues
M M
MM
Soares
I S
IS
D000818:Animals; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D006801:Humans; D007114:Immunization; D017780:Malaria Vaccines / Q000276:immunology*; D020066:Merozoite Surface Protein 1 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010966:Plasmodium vivax / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*
D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic