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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Hodgson, Susanne H. ; Ewer, Katie J. ; Bliss, Carly M. ; Edwards, Nick J. ; Rampling, Thomas ; Anagnostou, Nicholas A. ; de Barra, Eoghan ; Havelock, Tom ; Bowyer, Georgina ; Poulton, Ian D. ; de Cassan, Simone ; Longley, Rhea ; Illingworth, Joseph J. ; Douglas, Alexander D. ; Mange, Pooja B. ; Collins, Katharine A. ; Roberts, Rachel ; Gerry, Stephen ; Berrie, Eleanor ; Moyle, Sarah ; Colloca, Stefano ; Cortese, Riccardo ; Sinden, Robert E. ; Gilbert, Sarah C. ; Bejon, Philip ; Lawrie, Alison M. ; Nicosia, Alfredo ; Faust, Saul N. ; Hill, Adrian V. S. (2014)
  • Publisher: Oxford University Press
  • Journal: The Journal of Infectious Diseases, volume 211, issue 7, pages 1,076-1,086 (issn: 0022-1899, eissn: 1537-6613)
  • Related identifiers: doi: 10.1093/infdis/jiu579, pmc: PMC4354983
  • Subject: CS | vaccine | ChAd63 | ME-TRAP | P. falciparum | Parasites | MVA | malaria | Major Articles and Brief Reports | CHMI
    mesheuropmc: complex mixtures | viruses

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. Clinical Trials Registration. NCT01623557.
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