Prime-boost vaccination with recombinant protein and adenovirus-vector expressing Plasmodium vivax circumsporozoite protein (CSP) partially protects mice against Pb/Pv sporozoite challenge.
Tarsila Mendes de CamargoElisângela Oliveira de FreitasAlba Marina GimenezLuciana Chagas LimaKarina de Almeida CaramicoKátia Sanches FrançosoOscar Bruna-RomeroChiara AndolinaFrancois H NostenLaurent RéniaHildegund C J ErtlRuth S NussenzweigVictor NussenzweigMauricio M RodriguesArturo Reyes-SandovalIrene S SoaresPublished in: Scientific reports (2018)
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-AllFL) contained the fused repeat regions flanked by N- and C-terminal regions. The second construct (yPvCSP-AllCT) 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.
Keyphrases
- plasmodium falciparum
- high fat diet induced
- wild type
- heavy metals
- endothelial cells
- risk assessment
- stem cells
- computed tomography
- immune response
- insulin resistance
- early stage
- protein protein
- adipose tissue
- metabolic syndrome
- type diabetes
- dendritic cells
- small molecule
- multidrug resistant
- cell free
- amino acid
- mesenchymal stem cells
- cell therapy
- recombinant human
- bone marrow
- zika virus
- aedes aegypti
- gene therapy