Reduced blood-stage malaria growth and immune correlates in humans following RH5 vaccination.

Minassian, AM; Silk, SE; Barrett, JR; Nielsen, CM; Miura, K; Diouf, A; Loos, C; Fallon, JK; Michell, AR; White, MT; +40 more...Edwards, NJ; Poulton, ID; Mitton, CH; Payne, RO; Marks, MORCID logo; Maxwell-Scott, H; Querol-Rubiera, A; Bisnauthsing, K; Batra, R; Ogrina, T; Brendish, NJ; Themistocleous, Y; Rawlinson, TA; Ellis, KJ; Quinkert, D; Baker, M; Lopez Ramon, R; Ramos Lopez, F; Barfod, L; Folegatti, PM; Silman, D; Datoo, M; Taylor, IJ; Jin, J; Pulido, D; Douglas, AD; de Jongh, WA; Smith, R; Berrie, E; Noe, AR; Diggs, CL; Soisson, LA; Ashfield, R; Faust, SN; Goodman, AL; Lawrie, AM; Nugent, FL; Alter, G; Long, CA; Draper, SJ and (2021) Reduced blood-stage malaria growth and immune correlates in humans following RH5 vaccination. Med (New York, N.Y.), 2 (6). 701-719.e19. ISSN 2666-6359 DOI: 10.1016/j.medj.2021.03.014
Copy

BACKGROUND: Development of an effective vaccine against the pathogenic blood-stage infection of human malaria has proved challenging, and no candidate vaccine has affected blood-stage parasitemia following controlled human malaria infection (CHMI) with blood-stage Plasmodium falciparum. METHODS: We undertook a phase I/IIa clinical trial in healthy adults in the United Kingdom of the RH5.1 recombinant protein vaccine, targeting the P. falciparum reticulocyte-binding protein homolog 5 (RH5), formulated in AS01B adjuvant. We assessed safety, immunogenicity, and efficacy against blood-stage CHMI. Trial registered at ClinicalTrials.gov, NCT02927145. FINDINGS: The RH5.1/AS01B formulation was administered using a range of RH5.1 protein vaccine doses (2, 10, and 50 μg) and was found to be safe and well tolerated. A regimen using a delayed and fractional third dose, in contrast to three doses given at monthly intervals, led to significantly improved antibody response longevity over ∼2 years of follow-up. Following primary and secondary CHMI of vaccinees with blood-stage P. falciparum, a significant reduction in parasite growth rate was observed, defining a milestone for the blood-stage malaria vaccine field. We show that growth inhibition activity measured in vitro using purified immunoglobulin G (IgG) antibody strongly correlates with in vivo reduction of the parasite growth rate and also identify other antibody feature sets by systems serology, including the plasma anti-RH5 IgA1 response, that are associated with challenge outcome. CONCLUSIONS: Our data provide a new framework to guide rational design and delivery of next-generation vaccines to protect against malaria disease. FUNDING: This study was supported by USAID, UK MRC, Wellcome Trust, NIAID, and the NIHR Oxford-BRC.


picture_as_pdf
1-s2.0-S2666634021001161-main.pdf
subject
Published Version
Available under Creative Commons: Attribution-NonCommercial-No Derivative Works 3.0

View Download

Atom BibTeX OpenURL ContextObject in Span Multiline CSV OpenURL ContextObject Dublin Core Dublin Core MPEG-21 DIDL Data Cite XML EndNote HTML Citation JSON MARC (ASCII) MARC (ISO 2709) METS MODS RDF+N3 RDF+N-Triples RDF+XML RIOXX2 XML Reference Manager Refer Simple Metadata ASCII Citation EP3 XML
Export

Downloads