Safety and Efficacy of Novel Malaria Vaccine Regimens of RTS,S/AS01B alone, or with Concomitant ChAd63-MVA Vectored Vaccines Expressing ME-TRAP
We assessed a combination multi-stage malaria vaccine schedule in which RTS,S/AS01B was given concomitantly with viral vectors expressing multiple-epitope thrombospondin-related adhesion protein (ME-TRAP) in a 0-month, 1-month, and 2-month schedule. RTS,S/AS01B was given as either three full doses o...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
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Nature Publishing Group
2018
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| _version_ | 1826304122930855936 |
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| author | Rampling, T Ewer, KJ Bowyer, G Edwards, N Wright, D Sridhar, S Payne, R Powlson, J Bliss, C Venkatraman, N Poulton, I de Graaf, H Gbesemete, D Grobbelaar, A Davis, H Roberts, R Angus, B Ivinson, K Weltzin, R Rajkumar, B-Y Wille-Reece, U Lee, C Ockenhouse, C Sinden, R Gerry, S Lawrie, A Vekemans, J Morelle, D Lievens, M Ballou, RW Lewis, DJM Cooke, GS Faust, SN Gilbert, S Hill, A |
| author_facet | Rampling, T Ewer, KJ Bowyer, G Edwards, N Wright, D Sridhar, S Payne, R Powlson, J Bliss, C Venkatraman, N Poulton, I de Graaf, H Gbesemete, D Grobbelaar, A Davis, H Roberts, R Angus, B Ivinson, K Weltzin, R Rajkumar, B-Y Wille-Reece, U Lee, C Ockenhouse, C Sinden, R Gerry, S Lawrie, A Vekemans, J Morelle, D Lievens, M Ballou, RW Lewis, DJM Cooke, GS Faust, SN Gilbert, S Hill, A |
| author_sort | Rampling, T |
| collection | OXFORD |
| description | We assessed a combination multi-stage malaria vaccine schedule in which RTS,S/AS01B was given concomitantly with viral vectors expressing multiple-epitope thrombospondin-related adhesion protein (ME-TRAP) in a 0-month, 1-month, and 2-month schedule. RTS,S/AS01B was given as either three full doses or with a fractional (1/5th) third dose. Efficacy was assessed by controlled human malaria infection (CHMI). Safety and immunogenicity of the vaccine regimen was also assessed. Forty-one malaria-naive adults received RTS,S/AS01B at 0, 4 and 8 weeks, either alone (Groups 1 and 2) or with ChAd63 ME-TRAP at week 0, and modified vaccinia Ankara (MVA) ME-TRAP at weeks 4 and 8 (Groups 3 and 4). Groups 2 and 4 received a fractional (1/5th) dose of RTS,S/AS01B at week 8. CHMI was delivered by mosquito bite 11 weeks after first vaccination. Vaccine efficacy was 6/8 (75%), 8/9 (88.9%), 6/10 (60%), and 5/9 (55.6%) of subjects in Groups 1, 2, 3, and 4, respectively. Immunological analysis indicated significant reductions in anti-circumsporozoite protein antibodies and TRAP-specific T cells at CHMI in the combination vaccine groups. This reduced immunogenicity was only observed after concomitant administration of the third dose of RTS,S/AS01B with the second dose of MVA ME-TRAP. The second dose of the MVA vector with a four-week interval caused significantly higher anti-vector immunity than the first and may have been the cause of immunological interference. Co-administration of ChAd63/MVA ME-TRAP with RTS,S/AS01B led to reduced immunogenicity and efficacy, indicating the need for evaluation of alternative schedules or immunization sites in attempts to generate optimal efficacy. |
| first_indexed | 2024-03-07T06:13:02Z |
| format | Journal article |
| id | oxford-uuid:f02c463e-ce14-422b-9d9f-b27315be215d |
| institution | University of Oxford |
| last_indexed | 2024-03-07T06:13:02Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:f02c463e-ce14-422b-9d9f-b27315be215d2022-03-27T11:45:57ZSafety and Efficacy of Novel Malaria Vaccine Regimens of RTS,S/AS01B alone, or with Concomitant ChAd63-MVA Vectored Vaccines Expressing ME-TRAPJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f02c463e-ce14-422b-9d9f-b27315be215dSymplectic Elements at OxfordNature Publishing Group2018Rampling, TEwer, KJBowyer, GEdwards, NWright, DSridhar, SPayne, RPowlson, JBliss, CVenkatraman, NPoulton, Ide Graaf, HGbesemete, DGrobbelaar, ADavis, HRoberts, RAngus, BIvinson, KWeltzin, RRajkumar, B-YWille-Reece, ULee, COckenhouse, CSinden, RGerry, SLawrie, AVekemans, JMorelle, DLievens, MBallou, RWLewis, DJMCooke, GSFaust, SNGilbert, SHill, AWe assessed a combination multi-stage malaria vaccine schedule in which RTS,S/AS01B was given concomitantly with viral vectors expressing multiple-epitope thrombospondin-related adhesion protein (ME-TRAP) in a 0-month, 1-month, and 2-month schedule. RTS,S/AS01B was given as either three full doses or with a fractional (1/5th) third dose. Efficacy was assessed by controlled human malaria infection (CHMI). Safety and immunogenicity of the vaccine regimen was also assessed. Forty-one malaria-naive adults received RTS,S/AS01B at 0, 4 and 8 weeks, either alone (Groups 1 and 2) or with ChAd63 ME-TRAP at week 0, and modified vaccinia Ankara (MVA) ME-TRAP at weeks 4 and 8 (Groups 3 and 4). Groups 2 and 4 received a fractional (1/5th) dose of RTS,S/AS01B at week 8. CHMI was delivered by mosquito bite 11 weeks after first vaccination. Vaccine efficacy was 6/8 (75%), 8/9 (88.9%), 6/10 (60%), and 5/9 (55.6%) of subjects in Groups 1, 2, 3, and 4, respectively. Immunological analysis indicated significant reductions in anti-circumsporozoite protein antibodies and TRAP-specific T cells at CHMI in the combination vaccine groups. This reduced immunogenicity was only observed after concomitant administration of the third dose of RTS,S/AS01B with the second dose of MVA ME-TRAP. The second dose of the MVA vector with a four-week interval caused significantly higher anti-vector immunity than the first and may have been the cause of immunological interference. Co-administration of ChAd63/MVA ME-TRAP with RTS,S/AS01B led to reduced immunogenicity and efficacy, indicating the need for evaluation of alternative schedules or immunization sites in attempts to generate optimal efficacy. |
| spellingShingle | Rampling, T Ewer, KJ Bowyer, G Edwards, N Wright, D Sridhar, S Payne, R Powlson, J Bliss, C Venkatraman, N Poulton, I de Graaf, H Gbesemete, D Grobbelaar, A Davis, H Roberts, R Angus, B Ivinson, K Weltzin, R Rajkumar, B-Y Wille-Reece, U Lee, C Ockenhouse, C Sinden, R Gerry, S Lawrie, A Vekemans, J Morelle, D Lievens, M Ballou, RW Lewis, DJM Cooke, GS Faust, SN Gilbert, S Hill, A Safety and Efficacy of Novel Malaria Vaccine Regimens of RTS,S/AS01B alone, or with Concomitant ChAd63-MVA Vectored Vaccines Expressing ME-TRAP |
| title | Safety and Efficacy of Novel Malaria Vaccine Regimens of RTS,S/AS01B alone, or with Concomitant ChAd63-MVA Vectored Vaccines Expressing ME-TRAP |
| title_full | Safety and Efficacy of Novel Malaria Vaccine Regimens of RTS,S/AS01B alone, or with Concomitant ChAd63-MVA Vectored Vaccines Expressing ME-TRAP |
| title_fullStr | Safety and Efficacy of Novel Malaria Vaccine Regimens of RTS,S/AS01B alone, or with Concomitant ChAd63-MVA Vectored Vaccines Expressing ME-TRAP |
| title_full_unstemmed | Safety and Efficacy of Novel Malaria Vaccine Regimens of RTS,S/AS01B alone, or with Concomitant ChAd63-MVA Vectored Vaccines Expressing ME-TRAP |
| title_short | Safety and Efficacy of Novel Malaria Vaccine Regimens of RTS,S/AS01B alone, or with Concomitant ChAd63-MVA Vectored Vaccines Expressing ME-TRAP |
| title_sort | safety and efficacy of novel malaria vaccine regimens of rts s as01b alone or with concomitant chad63 mva vectored vaccines expressing me trap |
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