Prime-boost vaccination with recombinant protein and adenovirus-vector expressing Plasmodium vivax circumsporozoite protein (CSP) partially protects mice against Pb/Pv sporozoite challenge

Author(s):Show less -

de Camargo, Tarsila Mendes ^[1] ; de Freitas, Elisangela Oliveira ^{[1, 2]} ; Gimenez, Alba Marina ^[3] ; Lima, Luciana Chagas ^[1] ; Caramico, Karina de Almeida ^[1] ; Francoso, Katia Sanches ^[1] ; Bruna-Romero, Oscar ^[4] ; Andolina, Chiara ^{[5, 6]} ; Nosten, Francois ^{[5, 6]} ; Renia, Laurent ^[7] ; Ertl, Hildegund C. J. ^[8] ; Nussenzweig, Ruth S. ^[9] ; Nussenzweig, Victor ^[9] ; Rodrigues, Mauricio M. ^[3] ; Reyes-Sandoval, Arturo ^[2] ; Soares, Irene S. ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo, SP - Brazil

^[2] Univ Oxford, Nuffield Dept Med, Jenner Inst, Henry Wellcome Bldg Mol Physiol, Roosevelt Dr, Oxford - England

^[3] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Ctr Cellular & Mol Therapy, Sao Paulo, SP - Brazil

^[4] Univ Fed Santa Catarina, Dept Microbiol & Immunol, Florianopolis, SC - Brazil

^[5] Mahidol Univ, Fac Trop Med, Shoklo Malaria Res Unit, Mahidol Oxford Trop Med Res Unit, Mae Sot - Thailand

^[6] Ctr Trop Med & Global Hlth, Nuffield Dept Med Res Bldg, Oxford - England

^[7] Agcy Sci Technol & Res, Singapore Immunol Network, Biopolis, Singapore - Singapore

^[8] Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 - USA

^[9] NYU, Sch Med, Dept Pathol, Michael Heidelberger Div, New York, NY - USA

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 8, JAN 18 2018.
• Web of Science Citations: 8

Abstract

Vaccine development against Plasmodium vivax malaria lags behind that for Plasmodium falciparum. To narrow this gap, we administered recombinant antigens based on P. vivax circumsporozoite protein (CSP) to mice. We expressed in Pichia pastoris two chimeric proteins by merging the three central repeat regions of different CSP alleles (VK210, VK247, and P. vivax-like). The first construct (yPvCSP-All(FL)) contained the fused repeat regions flanked by N- and C-terminal regions. The second construct (yPvCSP-All(CT)) contained the fused repeat regions and the C-terminal domain, plus RI region. Mice were vaccinated with three doses of yPvCSP in adjuvants Poly (I:C) or Montanide ISA720. We also used replication-defective adenovirus vectors expressing CSP of human serotype 5 (AdHu5) and chimpanzee serotype 68 (AdC68) for priming mice which were subsequently boosted twice with yPvCSP proteins in Poly (I:C) adjuvant. Regardless of the regime used, immunized mice generated high IgG titres specific to all CSP alleles. After challenge with P. berghei ANKA transgenic parasites expressing Pb/PvVK210 or Pb/PvVK247 sporozoites, significant time delays for parasitemia were observed in all vaccinated mice. These vaccine formulations should be clinically tried for their potential as protective universal vaccine against P. vivax malaria. (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: 09/15099-7 - Immunogenic evaluation of recombinant proteins expressed in Pichia pastoris based on Plasmodium vivax antigens from different parasite stages
• Grantee: Luciana Chagas de Lima
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 14/18102-7 - Preclinical tests of recombinant adenovirus-based protein and vaccine formulations expressing the Plasmodium vivax circumsporozoite protein
• Grantee: Alba Marina Gimenez
• Support Opportunities: Scholarships in Brazil - Post-Doctoral