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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Invasion-Inhibitory Antibodies Elicited by Immunization with Plasmodium vivax Apical Membrane Antigen-1 Expressed in Pichia pastoris Yeast

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Autor(es):
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Vicentin, Elaine C. [1] ; Francoso, Katia S. [1] ; Rocha, Mariana V. [1] ; Iourtov, Dmitri [2] ; dos Santos, Fernanda L. [2] ; Kubrusly, Flavia S. [2] ; Sakauchi, Maria A. [2] ; Raw, Isaias [2] ; Nosten, Francois [3, 4, 5] ; Renia, Laurent [6] ; Rodrigues, Mauricio M. [7] ; Russell, Bruce [6, 8] ; Soares, Irene S. [1]
Número total de Autores: 13
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Anal Clin & Toxicol, Sao Paulo - Brazil
[2] Inst Butantan, Sao Paulo - Brazil
[3] Shoklo Malaria Res Unit SMRU, Mae Sot, Tak Province - Thailand
[4] Mahidol Oxford Univ, Res Unit, Bangkok - Thailand
[5] Univ Oxford, Churchill Hosp, Ctr Trop Med, Oxford - England
[6] Agcy Sci Technol & Res, Singapore Immunol Network, Singapore - Singapore
[7] Univ Fed Sao Paulo, Escola Paulista Med, CTCMOL, Dept Microbiol Imunol & Parasitol, Sao Paulo - Brazil
[8] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Microbiol, Singapore 117595 - Singapore
Número total de Afiliações: 8
Tipo de documento: Artigo Científico
Fonte: Infection and Immunity; v. 82, n. 3, p. 1296-1307, MAR 2014.
Citações Web of Science: 32
Resumo

In a recent vaccine trial performed with African children, immunization with a recombinant protein based on Plasmodium falciparum apical membrane antigen 1 (AMA-1) conferred a significant degree of strain-specific resistance against malaria. To contribute to the efforts of generating a vaccine against Plasmodium vivax malaria, we expressed the ectodomain of P. vivax AMA-1 (PvAMA-1) as a secreted soluble protein in the methylotrophic yeast Pichia pastoris. Recognized by a high percentage of sera from individuals infected by P. vivax, this recombinant protein was found to have maintained its antigenicity. The immunogenicity of this protein was evaluated in mice using immunization protocols that included homologous and heterologous primeboost strategies with plasmid DNA and recombinant protein. We used the following formulations containing different adjuvants: aluminum salts (Alum), Bordetella pertussis monophosphoryl lipid A (MPLA), flagellin FliC from Salmonella enterica serovar Typhimurium, saponin Quil A, or incomplete Freund's adjuvant (IFA). The formulations containing the adjuvants Quil A or IFA elicited the highest IgG antibody titers. Significant antibody titers were also obtained using a formulation developed for human use containing MPLA or Alum plus MPLA. Recombinant PvAMA-1 produced under ``conditions of good laboratory practice{''} provided a good yield, high purity, low endotoxin levels, and no microbial contaminants and reproduced the experimental immunizations. Most relevant for vaccine development was the fact that immunization with PvAMA-1 elicited invasioninhibitory antibodies against different Asian isolates of P. vivax. Our results show that AMA-1 expressed in P. pastoris is a promising antigen for use in future preclinical and clinical studies. (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
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 12/13032-5 - Geração e análise da imunogenicidade de proteínas recombinantes baseadas nas diferentes formas alélicas do antígeno circumsporozoíta de Plasmodium vivax visando o desenvolvimento de uma vacina universal contra malária
Beneficiário:Irene da Silva Soares
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 08/05613-2 - Avaliação da imunogenicidade do antígeno 1 de membrana apical de Plasmodium vivax(PvAMA-1): testes de protocolos heterólogos de indução e reforço utilizando DNA plasmidial e/ou proteína recombinante
Beneficiário:Irene da Silva Soares
Linha de fomento: Auxílio à Pesquisa - Regular