Immunogenicity of Recombinant Proteins Consisting of Plasmodium vivax Circumsporozoite Protein Allelic Variant-Derived Epitopes Fused with Salmonella enterica Serovar Typhimurium Flagellin

Autor(es)

Andrade Leal, Monica Teixeira ^{[1, 2]} ; Ariza Camacho, Ariane Guglielmi ^{[1, 2]} ; Teixeira, Lais Helena ^{[2, 3]} ; Bargieri, Daniel Youssef ^{[1, 2]} ; Soares, Irene Silva ^[4] ; Tararam, Cibele Aparecida ^{[1, 2]} ; Rodrigues, Mauricio M. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Escola Paulista Med, Ctr Terapia Celular & Mol CTCMol, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Ciencia Biomed, Dept Imunol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Anal Clin & Toxicol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Clinical and Vaccine Immunology; v. 20, n. 9, p. 1418-1425, SEP 2013.
• Citações Web of Science: 13

Resumo

A Plasmodium falciparum circumsporozoite protein (CSP)-based recombinant fusion vaccine is the first malaria vaccine to reach phase III clinical trials. Resistance to infection correlated with the production of antibodies to the immunodominant central repeat region of the CSP. In contrast to P. falciparum, vaccine development against the CSP of Plasmodium vivax malaria is far behind. Based on this gap in our knowledge, we generated a recombinant chimeric protein containing the immunodominant central repeat regions of the P. vivax CSP fused to Salmonella enterica serovar Typhimurium-derived flagellin (FliC) to activate the innate immune system. The recombinant proteins that were generated contained repeat regions derived from each of the 3 different allelic variants of the P. vivax CSP or a fusion of regions derived from each of the 3 allelic forms. Mice were subcutaneously immunized with the fusion proteins alone or in combination with the Toll-like receptor 3 (TLR-3) agonist poly(I.C), and the anti-CSP serum IgG response was measured. Immunization with a mixture of the 3 recombinant proteins, each containing immunodominant epitopes derived from a single allelic variant, rather than a single recombinant protein carrying a fusion of regions derived from each of 3 allelic forms elicited a stronger immune response. This response was independent of TLR-4 but required TLR-5/MyD88 activation. Antibody titers significantly increased when poly(I.C) was used as an adjuvant with a mixture of the 3 recombinant proteins. These recombinant fusion proteins are novel candidates for the development of an effective malaria vaccine against P. vivax. (AU)

• Processo FAPESP: 09/15132-4 - Geração e análise da imunogenicidade de proteínas recombinantes baseadas nas diferentes formas do antígeno circumsporozoíta de Plasmodium vivax visando o desenvolvimento de uma vacina universal contra malária
• Beneficiário: Maurício Martins Rodrigues
• Modalidade de apoio: Auxílio à Pesquisa - Temático