BibTex format
@article{Rampling:2018:10.1038/s41541-018-0084-2,
author = {Rampling, T and Ewer, KJ and Bowyer, G and Edwards, NJ and Wright, D and Sridhar, S and Payne, R and Powlson, J and Bliss, C and Venkatraman, N and Poulton, ID and de, Graaf H and Gbesemete, D and Grobbelaar, A and Davies, H and Roberts, R and Angus, B and Ivinson, K and Weltzin, R and Rajkumar, B-Y and Wille-Reece, U and Lee, C and Ockenhouse, C and Sinden, R and Gerry, SC and Lawrie, A and Vekemans, J and Morelle, D and Lievens, M and Ballou, RW and Lewis, DJM and Cooke, GS and Faust, SN and Hill, AV},
doi = {10.1038/s41541-018-0084-2},
journal = {npj Vaccines},
title = {Safety and efficacy of novel malaria vaccine regimens of RTS, S/AS01B alone, or with concomitant ChAd63-MVA-vectored vaccines expressing ME-TRAP},
url = {http://dx.doi.org/10.1038/s41541-018-0084-2},
volume = {3},
year = {2018}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - 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.
AU - Rampling,T
AU - Ewer,KJ
AU - Bowyer,G
AU - Edwards,NJ
AU - Wright,D
AU - Sridhar,S
AU - Payne,R
AU - Powlson,J
AU - Bliss,C
AU - Venkatraman,N
AU - Poulton,ID
AU - de,Graaf H
AU - Gbesemete,D
AU - Grobbelaar,A
AU - Davies,H
AU - Roberts,R
AU - Angus,B
AU - Ivinson,K
AU - Weltzin,R
AU - Rajkumar,B-Y
AU - Wille-Reece,U
AU - Lee,C
AU - Ockenhouse,C
AU - Sinden,R
AU - Gerry,SC
AU - Lawrie,A
AU - Vekemans,J
AU - Morelle,D
AU - Lievens,M
AU - Ballou,RW
AU - Lewis,DJM
AU - Cooke,GS
AU - Faust,SN
AU - Hill,AV
DO - 10.1038/s41541-018-0084-2
PY - 2018///
SN - 2059-0105
TI - Safety and efficacy of novel malaria vaccine regimens of RTS, S/AS01B alone, or with concomitant ChAd63-MVA-vectored vaccines expressing ME-TRAP
T2 - npj Vaccines
UR - http://dx.doi.org/10.1038/s41541-018-0084-2
VL - 3
ER -