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

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

Author Vicentin, Elaine C. Google Scholar
Francoso, Katia S. Google Scholar
Rocha, Mariana V. Google Scholar
Iourtov, Dmitri Google Scholar
Santos, Fernanda L. dos Google Scholar
Kubrusly, Flavia S. Google Scholar
Sakauchi, Maria A. Google Scholar
Raw, Isaias Google Scholar
Nosten, Francois Google Scholar
Renia, Laurent Google Scholar
Rodrigues, Mauricio M. Autor UNIFESP Google Scholar
Russell, Bruce Google Scholar
Soares, Irene S. Google Scholar
Institution Universidade de São Paulo (USP)
Inst Butantan
Shoklo Malaria Res Unit SMRU
Mahidol Oxford Univ
Univ Oxford
Agcy Sci Technol & Res
Universidade Federal de São Paulo (UNIFESP)
Natl Univ Singapore
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.
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
National Institute for Vaccine Development and Technology
Grant number FAPESP: FAPESP 2008/05613-2
FAPESP: 2009/12132-4
FAPESP: 2010/09893-0
FAPESP: 2012/13032-5
Date 2014-03-01
Published in Infection and Immunity. Washington: Amer Soc Microbiology, v. 82, n. 3, p. 1296-1307, 2014.
ISSN 0019-9567 (Sherpa/Romeo, impact factor)
Publisher Amer Soc Microbiology
Extent 1296-1307
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000333190900040

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