Adjuvant requirement for successful immunization with recombinant derivatives of Plasmodium vivax merozoite surface protein-1 delivered via the intranasal route.
Recently, we generated two bacterial recombinant proteins expressing 89 amino acids of the C-terminal domain of the Plasmodium vivax merozoite surface protein-1 and the hexa-histidine tag (His6MSP1(19)). One of these recombinant proteins contained also the amino acid sequence of the universal pan allelic T-cell epitope (His6MSP1(19)-PADRE). In the present study, we evaluated the immunogenic properties of these antigens when administered via the intra-nasal route in the presence of distinct adjuvant formulations. We found that C57BL/6 mice immunized with either recombinant proteins in the presence of the adjuvants cholera toxin (CT) or the Escherichia coli heat labile toxin (LT) developed high and long lasting titers of specific serum antibodies. The induced immune responses reached maximum levels after three immunizing doses with a prevailing IgG1 subclass response. In contrast, mice immunized by intranasal route with His6MSP1(19)-PADRE in the presence of the synthetic oligonucleotides adjuvant CpG ODN 1826 developed lower antibody titers but when combined to CT, CpG addition resulted in enhanced IgG responses characterized by lower IgG1 levels. Considering the limitations of antigens formulations that can be used in humans, mucosal adjuvants can be a reliable alternative for the development of new strategies of immunization using recombinant proteins of P. vivax.
Bargieri
Daniel Y
DY
Centro Interdisiciplinar de Terapia Gênica, Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Mirassol 207, 04044-010 São Paulo, Brasil. .
Rosa
Daniela S
DS
Lasaro
Melissa Ang Simões
MA
Ferreira
Luis Carlos S
LC
Soares
Irene S
IS
Rodrigues
Mauricio M
MM
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D018928:Immunity, Mucosal / Q000187:drug effects; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016780:Malaria, Vivax / Q000276:immunology* / Q000517:prevention & control; D020066:Merozoite Surface Protein 1 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010966:Plasmodium vivax / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
D000276:Adjuvants, Immunologic; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; C401223:PADRE 45; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic