Rational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge models
Development of a protective and broadly-acting vaccine against the most widely distributed human malaria parasite, Plasmodium vivax, will be a major step towards malaria elimination. However, a P. vivax vaccine has remained elusive by the scarcity of pre-clinical models to test protective efficacy a...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Nature Publishing Group
2017
|
| _version_ | 1797058754214100992 |
|---|---|
| author | Salman, A Montoya-Díaz, E West, H Lall, A Atcheson, E Lopez-Camacho, C Ramesar, J Bauza, K Collins, K Brod, F Reis, F Pappas, L González-Cerón, L Janse, C Hill, A Khan, S Reyes-Sandoval, A |
| author_facet | Salman, A Montoya-Díaz, E West, H Lall, A Atcheson, E Lopez-Camacho, C Ramesar, J Bauza, K Collins, K Brod, F Reis, F Pappas, L González-Cerón, L Janse, C Hill, A Khan, S Reyes-Sandoval, A |
| author_sort | Salman, A |
| collection | OXFORD |
| description | Development of a protective and broadly-acting vaccine against the most widely distributed human malaria parasite, Plasmodium vivax, will be a major step towards malaria elimination. However, a P. vivax vaccine has remained elusive by the scarcity of pre-clinical models to test protective efficacy and support further clinical trials. In this study, we report the development of a highly protective CSP-based P. vivax vaccine, a virus-like particle (VLP) known as Rv21, able to provide 100% sterile protection against a stringent sporozoite challenge in rodent models to malaria, where IgG2a antibodies were associated with protection in absence of detectable PvCSP-specific T cell responses. Additionally, we generated two novel transgenic rodent P. berghei parasite lines, where the P. berghei csp gene coding sequence has been replaced with either full-length P. vivax VK210 or the allelic VK247 csp that additionally express GFP-Luciferase. Efficacy of Rv21 surpassed viral-vectored vaccination using ChAd63 and MVA. We show for the first time that a chimeric VK210/247 antigen can elicit high level cross-protection against parasites expressing either CSP allele, which provide accessible and affordable models suitable to support the development of P. vivax vaccines candidates. Rv21 is progressing to GMP production and has entered a path towards clinical evaluation. |
| first_indexed | 2024-03-06T19:54:47Z |
| format | Journal article |
| id | oxford-uuid:253088ab-439a-43fe-82a6-56f80cdb1876 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:54:47Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:253088ab-439a-43fe-82a6-56f80cdb18762022-03-26T11:54:22ZRational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge modelsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:253088ab-439a-43fe-82a6-56f80cdb1876EnglishSymplectic Elements at OxfordNature Publishing Group2017Salman, AMontoya-Díaz, EWest, HLall, AAtcheson, ELopez-Camacho, CRamesar, JBauza, KCollins, KBrod, FReis, FPappas, LGonzález-Cerón, LJanse, CHill, AKhan, SReyes-Sandoval, ADevelopment of a protective and broadly-acting vaccine against the most widely distributed human malaria parasite, Plasmodium vivax, will be a major step towards malaria elimination. However, a P. vivax vaccine has remained elusive by the scarcity of pre-clinical models to test protective efficacy and support further clinical trials. In this study, we report the development of a highly protective CSP-based P. vivax vaccine, a virus-like particle (VLP) known as Rv21, able to provide 100% sterile protection against a stringent sporozoite challenge in rodent models to malaria, where IgG2a antibodies were associated with protection in absence of detectable PvCSP-specific T cell responses. Additionally, we generated two novel transgenic rodent P. berghei parasite lines, where the P. berghei csp gene coding sequence has been replaced with either full-length P. vivax VK210 or the allelic VK247 csp that additionally express GFP-Luciferase. Efficacy of Rv21 surpassed viral-vectored vaccination using ChAd63 and MVA. We show for the first time that a chimeric VK210/247 antigen can elicit high level cross-protection against parasites expressing either CSP allele, which provide accessible and affordable models suitable to support the development of P. vivax vaccines candidates. Rv21 is progressing to GMP production and has entered a path towards clinical evaluation. |
| spellingShingle | Salman, A Montoya-Díaz, E West, H Lall, A Atcheson, E Lopez-Camacho, C Ramesar, J Bauza, K Collins, K Brod, F Reis, F Pappas, L González-Cerón, L Janse, C Hill, A Khan, S Reyes-Sandoval, A Rational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge models |
| title | Rational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge models |
| title_full | Rational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge models |
| title_fullStr | Rational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge models |
| title_full_unstemmed | Rational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge models |
| title_short | Rational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge models |
| title_sort | rational development of a protective p vivax vaccine evaluated with transgenic rodent parasite challenge models |
| work_keys_str_mv | AT salmana rationaldevelopmentofaprotectivepvivaxvaccineevaluatedwithtransgenicrodentparasitechallengemodels AT montoyadiaze rationaldevelopmentofaprotectivepvivaxvaccineevaluatedwithtransgenicrodentparasitechallengemodels AT westh rationaldevelopmentofaprotectivepvivaxvaccineevaluatedwithtransgenicrodentparasitechallengemodels AT lalla rationaldevelopmentofaprotectivepvivaxvaccineevaluatedwithtransgenicrodentparasitechallengemodels AT atchesone rationaldevelopmentofaprotectivepvivaxvaccineevaluatedwithtransgenicrodentparasitechallengemodels AT lopezcamachoc rationaldevelopmentofaprotectivepvivaxvaccineevaluatedwithtransgenicrodentparasitechallengemodels AT ramesarj rationaldevelopmentofaprotectivepvivaxvaccineevaluatedwithtransgenicrodentparasitechallengemodels AT bauzak rationaldevelopmentofaprotectivepvivaxvaccineevaluatedwithtransgenicrodentparasitechallengemodels AT collinsk rationaldevelopmentofaprotectivepvivaxvaccineevaluatedwithtransgenicrodentparasitechallengemodels AT brodf rationaldevelopmentofaprotectivepvivaxvaccineevaluatedwithtransgenicrodentparasitechallengemodels AT reisf rationaldevelopmentofaprotectivepvivaxvaccineevaluatedwithtransgenicrodentparasitechallengemodels AT pappasl rationaldevelopmentofaprotectivepvivaxvaccineevaluatedwithtransgenicrodentparasitechallengemodels AT gonzalezceronl rationaldevelopmentofaprotectivepvivaxvaccineevaluatedwithtransgenicrodentparasitechallengemodels AT jansec rationaldevelopmentofaprotectivepvivaxvaccineevaluatedwithtransgenicrodentparasitechallengemodels AT hilla rationaldevelopmentofaprotectivepvivaxvaccineevaluatedwithtransgenicrodentparasitechallengemodels AT khans rationaldevelopmentofaprotectivepvivaxvaccineevaluatedwithtransgenicrodentparasitechallengemodels AT reyessandovala rationaldevelopmentofaprotectivepvivaxvaccineevaluatedwithtransgenicrodentparasitechallengemodels |