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Tailoring a P. vivax vaccine to enhance efficacy through a combination of a CSP Virus-Like Particle Rv21 and TRAP viral vectors

Abstract:
Vivax malaria remains one of the most serious and neglected tropical diseases, with 132 to 391 million clinical cases per year and 2.5 billion people at risk of infection. A vaccine against Plasmodium vivax could have more impact than any other intervention, and the use of a vaccine targeting multiple antigens may result in higher efficacy against sporozoite infection than targeting a single antigen. Here, two leading P. vivax preerythrocytic vaccine candidate antigens, the P. vivax circumsporozoite protein (PvCSP) and the thrombospondin-related adhesion protein (PvTRAP) were delivered as a combined vaccine. This strategy provided a dose-sparing effect, with 100% sterile protection in mice using doses that individually conferred low or no protection, as with the unadjuvanted antigens PvTRAP (0%) and PvCSP (50%), and reached protection similar to that of adjuvanted components. Efficacy against malaria infection was assessed using a new mouse challenge model consisting of a double-transgenic Plasmodium berghei parasite simultaneously expressing PvCSP and PvTRAP used in mice immunized with the virus-like particle (VLP) Rv21 previously reported to induce high efficacy in mice using Matrix-M adjuvant, while PvTRAP was concomitantly administered in chimpanzee adenovirus and modified vaccinia virus Ankara (MVA) vectors (viral-vectored TRAP, or vvTRAP) to support effective induction of T cells. We examined immunity elicited by these vaccines in the context of two adjuvants approved for human use (AddaVax and Matrix-M). Matrix-M supported the highest anti-PvCSP antibody titers when combined with Rv21, and, interestingly, mixing PvCSP Rv21 and PvTRAP viral vectors enhanced immunity to malaria over levels provided by single vaccines.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1128/iai.00114-18

Authors


More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
NDM; NDM Experimental Medicine
Role:
Author
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
NDM; NDM Experimental Medicine
Role:
Author
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
NDM; Jenner Institute
Role:
Author
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
NDM; Jenner Institute
Role:
Author
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
NDM; Jenner Institute
Role:
Author


More from this funder
Funding agency for:
Reyes-Sandoval, A
Grant:
MR/N019008/1
More from this funder
Funding agency for:
Hill, A
Reyes-Sandoval, A
Grant:
095540/Z/11/Z
MR/N019008/1
More from this funder
Funding agency for:
Hill, A
Reyes-Sandoval, A
Grant:
095540/Z/11/Z
MR/N019008/1
More from this funder
Funding agency for:
Hill, A
Reyes-Sandoval, A
Grant:
095540/Z/11/Z
MR/N019008/1
More from this funder
Funding agency for:
Salman, A
Grant:
242095


Publisher:
American Society for Microbiology
Journal:
Infection and Immunity More from this journal
Volume:
86
Issue:
9
Article number:
e00114-18
Publication date:
2018-07-09
Acceptance date:
2018-07-09
DOI:
EISSN:
1098-5522
ISSN:
0019-9567
Pmid:
29986894


Language:
English
Keywords:
Pubs id:
pubs:868948
UUID:
uuid:57a6eccd-35e9-4bd3-9133-0d0952a8320c
Local pid:
pubs:868948
Source identifiers:
868948
Deposit date:
2018-07-22

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