Journal
SCIENTIFIC REPORTS
Volume 8, Issue -, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41598-017-19063-6
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Funding
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2012/13032-5]
- Instituto Nacional de Ciencia e Tecnologia de Vacinas (INCTV)
- FAPESP fellowships [2014/18102-7, 2009/15099-7]
- CNPq
- CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior) fellowship
- Medical Research Council, MRC [MR/N019008/1]
- Wellcome Trust [089179]
- Wellcome Trust Mahidol University Oxford Tropical Medicine Research Programme - Wellcome Trust
- Singapore Immunology Network (SIgN)
- Horizontal Programme on Infectious Diseases under Agency for Science, Technology and Research (A*STAR, Singapore)
- MRC [MR/N019008/1] Funding Source: UKRI
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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.
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