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

Author(s):Show less -

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]

Affiliation

^[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

• Document type: Journal article
• Source: Infection and Immunity; v. 82, n. 3, p. 1296-1307, MAR 2014.
• Web of Science Citations: 32

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. (AU)

• FAPESP's process: 12/13032-5 - Generation and analysis of the immunogenicity of recombinant proteins based on the different allelic forms of the circumsporozoite antigen of Plasmodium vivax aiming at the development of a universal vaccine against malaria
• Grantee: Irene da Silva Soares
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 10/09893-0 - Analysis of the immune response induced by experimental immunization with recombinant antigens of Plasmodium vivax
• Grantee: Irene da Silva Soares
• Support Opportunities: Regular Research Grants
• FAPESP's process: 08/05613-2 - Evaluation of the immunogenicity of the Plasmodium vivax Apical Membrane Antigen 1 (PvAMA-1): heterologous prime-boost strategy using DNA and/or recombinant protein
• Grantee: Irene da Silva Soares
• Support Opportunities: Regular Research Grants