Evaluation of the efficacy of chad63-mva vectored vaccines expressing circumsporozoite protein and me-trap against controlled human malaria infection in malaria-naive individuals
<p style="text-align:justify;"> <b>Background:</b> Circumsporozoite protein (CS) is the antigenic target for RTS,S, the most advanced malaria vaccine to date. Heterologous prime-boost with the viral vectors simian adenovirus 63 (ChAd63)-modified vaccinia virus Ankara (MV...
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| Formatua: | Journal article |
| Hizkuntza: | English |
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Oxford University Press
2014
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| _version_ | 1826303548475834368 |
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| author | Hodgson, SH Ewer, KJ Bliss, CM Edwards, NJ Rampling, T Anagnostou, NA De Barra, E Havelock, T Bowyer, G Poulton, ID De Cassan, S Longley, R Illingworth, JJ Douglas, AD Mange, PB Collins, KA Roberts, R Gerry, S Berrie, E Moyle, S Colloca, S Cortese, R Sinden, RE Gilbert, SC Bejon, P Lawrie, AM Nicosia, A Faust, SN Hill, AV |
| author_facet | Hodgson, SH Ewer, KJ Bliss, CM Edwards, NJ Rampling, T Anagnostou, NA De Barra, E Havelock, T Bowyer, G Poulton, ID De Cassan, S Longley, R Illingworth, JJ Douglas, AD Mange, PB Collins, KA Roberts, R Gerry, S Berrie, E Moyle, S Colloca, S Cortese, R Sinden, RE Gilbert, SC Bejon, P Lawrie, AM Nicosia, A Faust, SN Hill, AV |
| author_sort | Hodgson, SH |
| collection | OXFORD |
| description | <p style="text-align:justify;"> <b>Background:</b> Circumsporozoite protein (CS) is the antigenic target for RTS,S, the most advanced malaria vaccine to date. Heterologous prime-boost with the viral vectors simian adenovirus 63 (ChAd63)-modified vaccinia virus Ankara (MVA) is the most potent inducer of T-cells in humans, demonstrating significant efficacy when expressing the preerythrocytic antigen insert multiple epitope–thrombospondin-related adhesion protein (ME-TRAP). We hypothesized that ChAd63-MVA containing CS may result in a significant clinical protective efficacy.<br/> <b>Methods:</b> We conducted an open-label, 2-site, partially randomized Plasmodium falciparum sporozoite controlled human malaria infection (CHMI) study to compare the clinical efficacy of ChAd63-MVA CS with ChAd63-MVA ME-TRAP.<br/> <b>Results:</b> One of 15 vaccinees (7%) receiving ChAd63-MVA CS and 2 of 15 (13%) receiving ChAd63-MVA ME-TRAP achieved sterile protection after CHMI. Three of 15 vaccinees (20%) receiving ChAd63-MVA CS and 5 of 15 (33%) receiving ChAd63-MVA ME-TRAP demonstrated a delay in time to treatment, compared with unvaccinated controls. In quantitative polymerase chain reaction analyses, ChAd63-MVA CS was estimated to reduce the liver parasite burden by 69%–79%, compared with 79%–84% for ChAd63-MVA ME-TRAP.<br/> <b>Conclusions:</b> ChAd63-MVA CS does reduce the liver parasite burden, but ChAd63-MVA ME-TRAP remains the most promising antigenic insert for a vectored liver-stage vaccine. Detailed analyses of parasite kinetics may allow detection of smaller but biologically important differences in vaccine efficacy that can influence future vaccine development.<br/> <b>Clinical Trials Registration:</b> NCT01623557. </p> |
| first_indexed | 2024-03-07T06:04:22Z |
| format | Journal article |
| id | oxford-uuid:ed531bf5-3a33-4ef7-a1a1-651b82685d9b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:04:22Z |
| publishDate | 2014 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:ed531bf5-3a33-4ef7-a1a1-651b82685d9b2022-03-27T11:24:12ZEvaluation of the efficacy of chad63-mva vectored vaccines expressing circumsporozoite protein and me-trap against controlled human malaria infection in malaria-naive individualsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ed531bf5-3a33-4ef7-a1a1-651b82685d9bEnglishSymplectic Elements at OxfordOxford University Press2014Hodgson, SHEwer, KJBliss, CMEdwards, NJRampling, TAnagnostou, NADe Barra, EHavelock, TBowyer, GPoulton, IDDe Cassan, SLongley, RIllingworth, JJDouglas, ADMange, PBCollins, KARoberts, RGerry, SBerrie, EMoyle, SColloca, SCortese, RSinden, REGilbert, SCBejon, PLawrie, AMNicosia, AFaust, SNHill, AV <p style="text-align:justify;"> <b>Background:</b> Circumsporozoite protein (CS) is the antigenic target for RTS,S, the most advanced malaria vaccine to date. Heterologous prime-boost with the viral vectors simian adenovirus 63 (ChAd63)-modified vaccinia virus Ankara (MVA) is the most potent inducer of T-cells in humans, demonstrating significant efficacy when expressing the preerythrocytic antigen insert multiple epitope–thrombospondin-related adhesion protein (ME-TRAP). We hypothesized that ChAd63-MVA containing CS may result in a significant clinical protective efficacy.<br/> <b>Methods:</b> We conducted an open-label, 2-site, partially randomized Plasmodium falciparum sporozoite controlled human malaria infection (CHMI) study to compare the clinical efficacy of ChAd63-MVA CS with ChAd63-MVA ME-TRAP.<br/> <b>Results:</b> One of 15 vaccinees (7%) receiving ChAd63-MVA CS and 2 of 15 (13%) receiving ChAd63-MVA ME-TRAP achieved sterile protection after CHMI. Three of 15 vaccinees (20%) receiving ChAd63-MVA CS and 5 of 15 (33%) receiving ChAd63-MVA ME-TRAP demonstrated a delay in time to treatment, compared with unvaccinated controls. In quantitative polymerase chain reaction analyses, ChAd63-MVA CS was estimated to reduce the liver parasite burden by 69%–79%, compared with 79%–84% for ChAd63-MVA ME-TRAP.<br/> <b>Conclusions:</b> ChAd63-MVA CS does reduce the liver parasite burden, but ChAd63-MVA ME-TRAP remains the most promising antigenic insert for a vectored liver-stage vaccine. Detailed analyses of parasite kinetics may allow detection of smaller but biologically important differences in vaccine efficacy that can influence future vaccine development.<br/> <b>Clinical Trials Registration:</b> NCT01623557. </p> |
| spellingShingle | Hodgson, SH Ewer, KJ Bliss, CM Edwards, NJ Rampling, T Anagnostou, NA De Barra, E Havelock, T Bowyer, G Poulton, ID De Cassan, S Longley, R Illingworth, JJ Douglas, AD Mange, PB Collins, KA Roberts, R Gerry, S Berrie, E Moyle, S Colloca, S Cortese, R Sinden, RE Gilbert, SC Bejon, P Lawrie, AM Nicosia, A Faust, SN Hill, AV Evaluation of the efficacy of chad63-mva vectored vaccines expressing circumsporozoite protein and me-trap against controlled human malaria infection in malaria-naive individuals |
| title | Evaluation of the efficacy of chad63-mva vectored vaccines expressing circumsporozoite protein and me-trap against controlled human malaria infection in malaria-naive individuals |
| title_full | Evaluation of the efficacy of chad63-mva vectored vaccines expressing circumsporozoite protein and me-trap against controlled human malaria infection in malaria-naive individuals |
| title_fullStr | Evaluation of the efficacy of chad63-mva vectored vaccines expressing circumsporozoite protein and me-trap against controlled human malaria infection in malaria-naive individuals |
| title_full_unstemmed | Evaluation of the efficacy of chad63-mva vectored vaccines expressing circumsporozoite protein and me-trap against controlled human malaria infection in malaria-naive individuals |
| title_short | Evaluation of the efficacy of chad63-mva vectored vaccines expressing circumsporozoite protein and me-trap against controlled human malaria infection in malaria-naive individuals |
| title_sort | evaluation of the efficacy of chad63 mva vectored vaccines expressing circumsporozoite protein and me trap against controlled human malaria infection in malaria naive individuals |
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