Safety and High Level Efficacy of the Combination Malaria Vaccine Regimen of RTS,S/AS01B With Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara Vectored Vaccines Expressing ME-TRAP
The need for a highly efficacious vaccine against Plasmodium falciparum remains pressing. In this controlled human malaria infection (CHMI) study, we assessed the safety, efficacy and immunogenicity of a schedule combining 2 distinct vaccine types in a staggered immunization regimen: one inducing hi...
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| Format: | Journal article |
| Sprache: | English |
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Oxford University Press
2016
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| _version_ | 1826263982605860864 |
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| author | Rampling, T Ewer, KJ Bowyer, G Bliss, CM Edwards, NJ Wright, D Payne, RO Venkatraman, N de Barra, E Snudden, CM Poulton, ID de Graaf, H Sukhtankar, P Roberts, R Ivinson, K Weltzin, R Rajkumar, BY Wille-Reece, U Lee, CK Ockenhouse, CF Sinden, RE Gerry, S Lawrie, AM Vekemans, J Morelle, D Lievens, M Ballou, RW Cooke, GS Faust, SN Gilbert, S Hill, AV |
| author_facet | Rampling, T Ewer, KJ Bowyer, G Bliss, CM Edwards, NJ Wright, D Payne, RO Venkatraman, N de Barra, E Snudden, CM Poulton, ID de Graaf, H Sukhtankar, P Roberts, R Ivinson, K Weltzin, R Rajkumar, BY Wille-Reece, U Lee, CK Ockenhouse, CF Sinden, RE Gerry, S Lawrie, AM Vekemans, J Morelle, D Lievens, M Ballou, RW Cooke, GS Faust, SN Gilbert, S Hill, AV |
| author_sort | Rampling, T |
| collection | OXFORD |
| description | The need for a highly efficacious vaccine against Plasmodium falciparum remains pressing. In this controlled human malaria infection (CHMI) study, we assessed the safety, efficacy and immunogenicity of a schedule combining 2 distinct vaccine types in a staggered immunization regimen: one inducing high-titer antibodies to circumsporozoite protein (RTS,S/AS01B) and the other inducing potent T-cell responses to thrombospondin-related adhesion protein (TRAP) by using a viral vector.Thirty-seven healthy malaria-naive adults were vaccinated with either a chimpanzee adenovirus 63 and modified vaccinia virus Ankara-vectored vaccine expressing a multiepitope string fused to TRAP and 3 doses of RTS,S/AS01B (group 1; n = 20) or 3 doses of RTS,S/AS01B alone (group 2; n = 17). CHMI was delivered by mosquito bites to 33 vaccinated subjects at week 12 after the first vaccination and to 6 unvaccinated controls.No suspected unexpected serious adverse reactions or severe adverse events related to vaccination were reported. Protective vaccine efficacy was observed in 14 of 17 subjects (82.4%) in group 1 and 12 of 16 subjects (75%) in group 2. All control subjects received a diagnosis of blood-stage malaria parasite infection. Both vaccination regimens were immunogenic. Fourteen protected subjects underwent repeat CHMI 6 months after initial CHMI; 7 of 8 (87.5%) in group 1 and 5 of 6 (83.3%) in group 2 remained protected.The high level of sterile efficacy observed in this trial is encouraging for further evaluation of combination approaches using these vaccine types.NCT01883609. |
| first_indexed | 2024-03-06T20:00:32Z |
| format | Journal article |
| id | oxford-uuid:2724b66e-098c-4a4f-8d98-c51f66a80da4 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:00:32Z |
| publishDate | 2016 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:2724b66e-098c-4a4f-8d98-c51f66a80da42022-03-26T12:05:07ZSafety and High Level Efficacy of the Combination Malaria Vaccine Regimen of RTS,S/AS01B With Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara Vectored Vaccines Expressing ME-TRAPJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2724b66e-098c-4a4f-8d98-c51f66a80da4EnglishSymplectic Elements at OxfordOxford University Press2016Rampling, TEwer, KJBowyer, GBliss, CMEdwards, NJWright, DPayne, ROVenkatraman, Nde Barra, ESnudden, CMPoulton, IDde Graaf, HSukhtankar, PRoberts, RIvinson, KWeltzin, RRajkumar, BYWille-Reece, ULee, CKOckenhouse, CFSinden, REGerry, SLawrie, AMVekemans, JMorelle, DLievens, MBallou, RWCooke, GSFaust, SNGilbert, SHill, AVThe need for a highly efficacious vaccine against Plasmodium falciparum remains pressing. In this controlled human malaria infection (CHMI) study, we assessed the safety, efficacy and immunogenicity of a schedule combining 2 distinct vaccine types in a staggered immunization regimen: one inducing high-titer antibodies to circumsporozoite protein (RTS,S/AS01B) and the other inducing potent T-cell responses to thrombospondin-related adhesion protein (TRAP) by using a viral vector.Thirty-seven healthy malaria-naive adults were vaccinated with either a chimpanzee adenovirus 63 and modified vaccinia virus Ankara-vectored vaccine expressing a multiepitope string fused to TRAP and 3 doses of RTS,S/AS01B (group 1; n = 20) or 3 doses of RTS,S/AS01B alone (group 2; n = 17). CHMI was delivered by mosquito bites to 33 vaccinated subjects at week 12 after the first vaccination and to 6 unvaccinated controls.No suspected unexpected serious adverse reactions or severe adverse events related to vaccination were reported. Protective vaccine efficacy was observed in 14 of 17 subjects (82.4%) in group 1 and 12 of 16 subjects (75%) in group 2. All control subjects received a diagnosis of blood-stage malaria parasite infection. Both vaccination regimens were immunogenic. Fourteen protected subjects underwent repeat CHMI 6 months after initial CHMI; 7 of 8 (87.5%) in group 1 and 5 of 6 (83.3%) in group 2 remained protected.The high level of sterile efficacy observed in this trial is encouraging for further evaluation of combination approaches using these vaccine types.NCT01883609. |
| spellingShingle | Rampling, T Ewer, KJ Bowyer, G Bliss, CM Edwards, NJ Wright, D Payne, RO Venkatraman, N de Barra, E Snudden, CM Poulton, ID de Graaf, H Sukhtankar, P Roberts, R Ivinson, K Weltzin, R Rajkumar, BY Wille-Reece, U Lee, CK Ockenhouse, CF Sinden, RE Gerry, S Lawrie, AM Vekemans, J Morelle, D Lievens, M Ballou, RW Cooke, GS Faust, SN Gilbert, S Hill, AV Safety and High Level Efficacy of the Combination Malaria Vaccine Regimen of RTS,S/AS01B With Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara Vectored Vaccines Expressing ME-TRAP |
| title | Safety and High Level Efficacy of the Combination Malaria Vaccine Regimen of RTS,S/AS01B With Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara Vectored Vaccines Expressing ME-TRAP |
| title_full | Safety and High Level Efficacy of the Combination Malaria Vaccine Regimen of RTS,S/AS01B With Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara Vectored Vaccines Expressing ME-TRAP |
| title_fullStr | Safety and High Level Efficacy of the Combination Malaria Vaccine Regimen of RTS,S/AS01B With Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara Vectored Vaccines Expressing ME-TRAP |
| title_full_unstemmed | Safety and High Level Efficacy of the Combination Malaria Vaccine Regimen of RTS,S/AS01B With Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara Vectored Vaccines Expressing ME-TRAP |
| title_short | Safety and High Level Efficacy of the Combination Malaria Vaccine Regimen of RTS,S/AS01B With Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara Vectored Vaccines Expressing ME-TRAP |
| title_sort | safety and high level efficacy of the combination malaria vaccine regimen of rts s as01b with chimpanzee adenovirus 63 and modified vaccinia ankara vectored vaccines expressing me trap |
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