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

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-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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41598-017-19063-6

Authors



More from this funder
Funding agency for:
Reyes-Sandoval, A
Grant:
MR/N019008/1
More from this funder
Funding agency for:
Reyes-Sandoval, A
Grant:
MR/N019008/1
More from this funder
Funding agency for:
Reyes-Sandoval, A
Grant:
MR/N019008/1
More from this funder
Funding agency for:
Andolina, C
Nosten, F
Grant:
089179
089179
More from this funder
Funding agency for:
Gimenez, A
Lima, L
Grant:
2014/18102-7
2009/15099-7


Publisher:
Nature Publishing Group
Journal:
Scientific Reports More from this journal
Volume:
8
Pages:
1-14
Publication date:
2018-01-18
Acceptance date:
2017-12-21
DOI:
EISSN:
2045-2322
ISSN:
2045-2322
Pmid:
29348479


Language:
English
Keywords:
Pubs id:
pubs:821284
UUID:
uuid:973e7216-7707-4c34-ab47-27d38edd9ccb
Local pid:
pubs:821284
Source identifiers:
821284
Deposit date:
2018-01-30

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