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

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

Author Andrade Leal, Monica Teixeira Autor UNIFESP Google Scholar
Ariza Camacho, Ariane Guglielmi Autor UNIFESP Google Scholar
Teixeira, Lais Helena Autor UNIFESP Google Scholar
Bargieri, Daniel Youssef Autor UNIFESP Google Scholar
Soares, Irene Silva Google Scholar
Tararam, Cibele Aparecida Autor UNIFESP Google Scholar
Rodrigues, Mauricio M. Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Abstract 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.
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 2009/15132-4
Date 2013-09-01
Published in Clinical and Vaccine Immunology. Washington: Amer Soc Microbiology, v. 20, n. 9, p. 1418-1425, 2013.
ISSN 1556-6811 (Sherpa/Romeo, impact factor)
Publisher Amer Soc Microbiology
Extent 1418-1425
Origin http://dx.doi.org/10.1128/CVI.00312-13
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000323699600011
URI http://repositorio.unifesp.br/handle/11600/36678

Show full item record




File

Name: WOS000323699600011.pdf
Size: 1.013Mb
Format: PDF
Description:
Open file

This item appears in the following Collection(s)

Search


Browse

Statistics

My Account