期刊
JOURNAL OF INFECTIOUS DISEASES
卷 211, 期 7, 页码 1076-1086出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiu579
关键词
malaria; P. falciparum; vaccine; ChAd63; MVA; ME-TRAP; CS; CHMI
资金
- PATH Malaria Vaccine Initiative
- United Kingdom National Institute of Health Research, through the Oxford Biomedical Research Centre [A91301]
- Wellcome Trust [084113/Z/07/Z, 45488/Z/05, 097940/Z/11/Z]
- National Institute for Health Research [NF-SI-0509-10233, NF-SI-0514-10158] Funding Source: researchfish
- Wellcome Trust [104750/Z/14/Z] Funding Source: researchfish
Background. 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. Methods. 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. Results. 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. Conclusions. 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.
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