Journal article
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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(Preview, Version of record, pdf, 1.4MB, Terms of use)
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- Publisher copy:
- 10.1128/iai.00114-18
Authors
+ Medical Research Council
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- Funding agency for:
- Reyes-Sandoval, A
- Grant:
- MR/N019008/1
+ Oxford Martin Fellow
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- Funding agency for:
- Hill, A
- Reyes-Sandoval, A
- Grant:
- 095540/Z/11/Z
- MR/N019008/1
+ Jenner Investigator
More from this funder
- Funding agency for:
- Hill, A
- Reyes-Sandoval, A
- Grant:
- 095540/Z/11/Z
- MR/N019008/1
+ Wellcome Trust
More from this funder
- Funding agency for:
- Hill, A
- Reyes-Sandoval, A
- Grant:
- 095540/Z/11/Z
- MR/N019008/1
- 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:
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1098-5522
- ISSN:
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0019-9567
- Pmid:
-
29986894
- Language:
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English
- Keywords:
- Pubs id:
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pubs:868948
- UUID:
-
uuid:57a6eccd-35e9-4bd3-9133-0d0952a8320c
- Local pid:
-
pubs:868948
- Source identifiers:
-
868948
- Deposit date:
-
2018-07-22
Terms of use
- Copyright holder:
- © 2018 Atcheson et al
- Copyright date:
- 2018
- Notes:
- This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
- Licence:
- CC Attribution (CC BY)
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