Antigenicity and Immunogenicity of Plasmodium vivax Merozoite Surface Protein-3

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Bitencourt, Amanda R. ^[1] ; Vicentin, Elaine C. ^[1] ; Jimenez, Maria C. ^[1] ; Ricci, Ricardo ^[1] ; Leite, Juliana A. ^[2] ; Costa, Fabio T. ^[2] ; Ferreira, Luis C. ^[3] ; Russell, Bruce ^{[4, 5]} ; Nosten, Francois ^{[6, 7]} ; Renia, Laurent ^[5] ; Galinski, Mary R. ^{[8, 9, 10]} ; Barnwell, John W. ^[11] ; Rodrigues, Mauricio M. ^[12] ; Soares, Irene S. ^[1]

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^[1] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Anal Clin & Toxicol, Sao Paulo - Brazil

^[2] Univ Estadual Campinas, Dept Genet Evolucao & Bioagentes, Inst Biol, Campinas, SP - Brazil

^[3] Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, BR-05508 Sao Paulo - Brazil

^[4] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Microbiol, Singapore 117595 - Singapore

^[5] Agcy Sci Technol & Res, Singapore Immunol Network, Biopolis, Singapore - Singapore

^[6] Churchill Hosp, Ctr Vaccinol & Trop Med, Oxford OX3 7LJ - England

^[7] Mahidol Oxford Univ Trop Med Res Programme, Shoklo Malaria Res Unit, Mae Sot - Thailand

^[8] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 - USA

^[9] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 - USA

^[10] Emory Univ, Dept Med, Div Infect Dis, Atlanta, GA 30322 - USA

^[11] Ctr Dis Control & Prevent, Malaria Branch, Div Parasit Dis, Chamblee, GA - USA

^[12] Univ Fed Sao Paulo, CTCMOL, Dept Microbiol Imunol & Parasitol, Escola Paulista Med, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 8, n. 2 FEB 14 2013.
• Citações Web of Science: 13

Resumo

A recent clinical trial in African children demonstrated the potential utility of merozoite surface protein (MSP)-3 as a vaccine against Plasmodium falciparum malaria. The present study evaluated the use of Plasmodium vivax MSP-3 (PvMSP-3) as a target antigen in vaccine formulations against malaria caused by P. vivax. Recombinant proteins representing MSP-3 alpha and MSP-3 beta of P. vivax were expressed as soluble histidine-tagged bacterial fusions. Antigenicity during natural infection was evaluated by detecting specific antibodies using sera from individuals living in endemic areas of Brazil. A large proportion of infected individuals presented IgG antibodies to PvMSP-3 alpha (68.2%) and at least 1 recombinant protein representing PvMSP-3 beta (79.1%). In spite of the large responder frequency, reactivity to both antigens was significantly lower than was observed for the immunodominant epitope present on the 19-kDa C-terminal region of PvMSP-1. Immunogenicity of the recombinant proteins was studied in mice in the absence or presence of different adjuvant formulations. PvMSP-3 beta, but not PvMSP-3 alpha, induced a TLR4-independent humoral immune response in the absence of any adjuvant formulation. The immunogenicity of the recombinant antigens were also tested in formulations containing different adjuvants (Alum, Salmonella enterica flagellin, CpG, Quil A, TiterMax (R) and incomplete Freunds adjuvant) and combinations of two adjuvants (Alum plus flagellin, and CpG plus flagellin). Recombinant PvMSP-3 alpha and PvMSP-3 beta elicited higher antibody titers capable of recognizing P. vivax-infected erythrocytes harvested from malaria patients. Our results confirm that P. vivax MSP-3 antigens are immunogenic during natural infection, and the corresponding recombinant proteins may be useful in elucidating their vaccine potential. (AU)

• Processo FAPESP: 10/09893-0 - Análise da resposta imune induzida pela imunização experimental com antígenos recombinantes de Plasmodium vivax
• Beneficiário: Irene da Silva Soares
• Modalidade de apoio: Auxílio à Pesquisa - Regular