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

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dc.contributor.author Vicentin, Elaine C.
dc.contributor.author Francoso, Katia S.
dc.contributor.author Rocha, Mariana V.
dc.contributor.author Iourtov, Dmitri
dc.contributor.author Santos, Fernanda L. dos
dc.contributor.author Kubrusly, Flavia S.
dc.contributor.author Sakauchi, Maria A.
dc.contributor.author Raw, Isaias
dc.contributor.author Nosten, Francois
dc.contributor.author Renia, Laurent
dc.contributor.author Rodrigues, Mauricio M. [UNIFESP]
dc.contributor.author Russell, Bruce
dc.contributor.author Soares, Irene S.
dc.date.accessioned 2016-01-24T14:35:21Z
dc.date.available 2016-01-24T14:35:21Z
dc.date.issued 2014-03-01
dc.identifier http://dx.doi.org/10.1128/IAI.01169-13
dc.identifier.citation Infection and Immunity. Washington: Amer Soc Microbiology, v. 82, n. 3, p. 1296-1307, 2014.
dc.identifier.issn 0019-9567
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/37464
dc.description.abstract 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. en
dc.description.sponsorship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorship National Institute for Vaccine Development and Technology
dc.format.extent 1296-1307
dc.language.iso eng
dc.publisher Amer Soc Microbiology
dc.relation.ispartof Infection and Immunity
dc.rights Acesso aberto
dc.title Invasion-Inhibitory Antibodies Elicited by Immunization with Plasmodium vivax Apical Membrane Antigen-1 Expressed in Pichia pastoris Yeast en
dc.type Artigo
dc.contributor.institution Universidade de São Paulo (USP)
dc.contributor.institution Inst Butantan
dc.contributor.institution Shoklo Malaria Res Unit SMRU
dc.contributor.institution Mahidol Oxford Univ
dc.contributor.institution Univ Oxford
dc.contributor.institution Agcy Sci Technol & Res
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Natl Univ Singapore
dc.description.affiliation Univ São Paulo, Fac Ciencias Farmaceut, Dept Anal Clin & Toxicol, São Paulo, Brazil
dc.description.affiliation Inst Butantan, São Paulo, Brazil
dc.description.affiliation Shoklo Malaria Res Unit SMRU, Mae Sot, Tak Province, Thailand
dc.description.affiliation Mahidol Oxford Univ, Res Unit, Bangkok, Thailand
dc.description.affiliation Univ Oxford, Churchill Hosp, Ctr Trop Med, Oxford, England
dc.description.affiliation Agcy Sci Technol & Res, Singapore Immunol Network, Singapore, Singapore
dc.description.affiliation Universidade Federal de São Paulo, Escola Paulista Med, CTCMOL, Dept Microbiol Imunol & Parasitol, São Paulo, Brazil
dc.description.affiliation Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Microbiol, Singapore 117595, Singapore
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Escola Paulista Med, CTCMOL, Dept Microbiol Imunol & Parasitol, São Paulo, Brazil
dc.description.sponsorshipID FAPESP: FAPESP 2008/05613-2
dc.description.sponsorshipID FAPESP: 2009/12132-4
dc.description.sponsorshipID FAPESP: 2010/09893-0
dc.description.sponsorshipID FAPESP: 2012/13032-5
dc.identifier.file WOS000333190900040.pdf
dc.identifier.doi 10.1128/IAI.01169-13
dc.description.source Web of Science
dc.identifier.wos WOS:000333190900040



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