Evaluation of Chimpanzee Adenovirus and MVA Expressing TRAP and CSP from <i>Plasmodium cynomolgi</i> to Prevent Malaria Relapse in Nonhuman Primates

<i>Plasmodium vivax </i>is the world’s most widely distributed human malaria parasite, with over 2.8 billion people at risk in Asia, the Americas, and Africa. The 80–90% new <i>P. vivax</i> malaria infections are due to relapses which suggest that a vaccine with high efficacy...

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Main Authors: Young Chan Kim, Barbara Dema, Roberto Rodriguez-Garcia, César López-Camacho, Fabiana M. S. Leoratti, Amar Lall, Edmond J. Remarque, Clemens H. M. Kocken, Arturo Reyes-Sandoval
Format: Article
Language:English
Published: MDPI AG 2020-07-01
Series:Vaccines
Subjects:
CSP
MVA
Online Access:https://www.mdpi.com/2076-393X/8/3/363
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spelling doaj-21a955844d644f07839aa23d15fb3aac2020-11-25T02:57:45ZengMDPI AGVaccines2076-393X2020-07-01836336310.3390/vaccines8030363Evaluation of Chimpanzee Adenovirus and MVA Expressing TRAP and CSP from <i>Plasmodium cynomolgi</i> to Prevent Malaria Relapse in Nonhuman PrimatesYoung Chan Kim0Barbara Dema1Roberto Rodriguez-Garcia2César López-Camacho3Fabiana M. S. Leoratti4Amar Lall5Edmond J. Remarque6Clemens H. M. Kocken7Arturo Reyes-Sandoval8The Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UKThe Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UKDepartment of Parasitology, Biomedical Primate Research Centre (BPRC), 2288 GJ Rijswijk, The NetherlandsThe Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UKThe Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UKThe Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UKDepartment of Parasitology, Biomedical Primate Research Centre (BPRC), 2288 GJ Rijswijk, The NetherlandsDepartment of Parasitology, Biomedical Primate Research Centre (BPRC), 2288 GJ Rijswijk, The NetherlandsThe Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK<i>Plasmodium vivax </i>is the world’s most widely distributed human malaria parasite, with over 2.8 billion people at risk in Asia, the Americas, and Africa. The 80–90% new <i>P. vivax</i> malaria infections are due to relapses which suggest that a vaccine with high efficacy against relapses by prevention of hypnozoite formation could lead to a significant reduction in the prevalence of <i>P. vivax </i>infections. Here, we describe the development of new recombinant ChAdOx1 and MVA vectors expressing <i>P. cynomolgi</i> Thrombospondin Related Adhesive Protein (PcTRAP) and the circumsporozoite protein (PcCSP). Both were shown to be immunogenic in mice prior to their assessment in rhesus macaques. We confirmed good vaccine-induced humoral and cellular responses after prime-boost vaccination in rhesus macaques prior to sporozoite challenge. Results indicate that there were no significant differences between mock-control and vaccinated animals after challenge, in terms of protective efficacy measured as the time taken to 1st patency, or as number of relapses. This suggests that under the conditions tested, the vaccination with PcTRAP and PcCSP using ChAdOx1 or MVA vaccine platforms do not protect against pre-erythrocytic malaria or relapses despite good immunogenicity induced by the viral-vectored vaccines.https://www.mdpi.com/2076-393X/8/3/363P. vivaxCircumsporozoite proteinCSPthrombospondin related adhesive protein: TRAPadenovirusesMVA
collection DOAJ
language English
format Article
sources DOAJ
author Young Chan Kim
Barbara Dema
Roberto Rodriguez-Garcia
César López-Camacho
Fabiana M. S. Leoratti
Amar Lall
Edmond J. Remarque
Clemens H. M. Kocken
Arturo Reyes-Sandoval
spellingShingle Young Chan Kim
Barbara Dema
Roberto Rodriguez-Garcia
César López-Camacho
Fabiana M. S. Leoratti
Amar Lall
Edmond J. Remarque
Clemens H. M. Kocken
Arturo Reyes-Sandoval
Evaluation of Chimpanzee Adenovirus and MVA Expressing TRAP and CSP from <i>Plasmodium cynomolgi</i> to Prevent Malaria Relapse in Nonhuman Primates
Vaccines
P. vivax
Circumsporozoite protein
CSP
thrombospondin related adhesive protein: TRAP
adenoviruses
MVA
author_facet Young Chan Kim
Barbara Dema
Roberto Rodriguez-Garcia
César López-Camacho
Fabiana M. S. Leoratti
Amar Lall
Edmond J. Remarque
Clemens H. M. Kocken
Arturo Reyes-Sandoval
author_sort Young Chan Kim
title Evaluation of Chimpanzee Adenovirus and MVA Expressing TRAP and CSP from <i>Plasmodium cynomolgi</i> to Prevent Malaria Relapse in Nonhuman Primates
title_short Evaluation of Chimpanzee Adenovirus and MVA Expressing TRAP and CSP from <i>Plasmodium cynomolgi</i> to Prevent Malaria Relapse in Nonhuman Primates
title_full Evaluation of Chimpanzee Adenovirus and MVA Expressing TRAP and CSP from <i>Plasmodium cynomolgi</i> to Prevent Malaria Relapse in Nonhuman Primates
title_fullStr Evaluation of Chimpanzee Adenovirus and MVA Expressing TRAP and CSP from <i>Plasmodium cynomolgi</i> to Prevent Malaria Relapse in Nonhuman Primates
title_full_unstemmed Evaluation of Chimpanzee Adenovirus and MVA Expressing TRAP and CSP from <i>Plasmodium cynomolgi</i> to Prevent Malaria Relapse in Nonhuman Primates
title_sort evaluation of chimpanzee adenovirus and mva expressing trap and csp from <i>plasmodium cynomolgi</i> to prevent malaria relapse in nonhuman primates
publisher MDPI AG
series Vaccines
issn 2076-393X
publishDate 2020-07-01
description <i>Plasmodium vivax </i>is the world’s most widely distributed human malaria parasite, with over 2.8 billion people at risk in Asia, the Americas, and Africa. The 80–90% new <i>P. vivax</i> malaria infections are due to relapses which suggest that a vaccine with high efficacy against relapses by prevention of hypnozoite formation could lead to a significant reduction in the prevalence of <i>P. vivax </i>infections. Here, we describe the development of new recombinant ChAdOx1 and MVA vectors expressing <i>P. cynomolgi</i> Thrombospondin Related Adhesive Protein (PcTRAP) and the circumsporozoite protein (PcCSP). Both were shown to be immunogenic in mice prior to their assessment in rhesus macaques. We confirmed good vaccine-induced humoral and cellular responses after prime-boost vaccination in rhesus macaques prior to sporozoite challenge. Results indicate that there were no significant differences between mock-control and vaccinated animals after challenge, in terms of protective efficacy measured as the time taken to 1st patency, or as number of relapses. This suggests that under the conditions tested, the vaccination with PcTRAP and PcCSP using ChAdOx1 or MVA vaccine platforms do not protect against pre-erythrocytic malaria or relapses despite good immunogenicity induced by the viral-vectored vaccines.
topic P. vivax
Circumsporozoite protein
CSP
thrombospondin related adhesive protein: TRAP
adenoviruses
MVA
url https://www.mdpi.com/2076-393X/8/3/363
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