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; Edwards, NJ; Poulton, ID; Mitton, CH; Payne, RO; Marks, M; 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

Journal article

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

Abstract:: 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 AS01_B adjuvant. We assessed safety, immunogenicity, and efficacy against blood-stage CHMI. Trial registered at ClinicalTrials.gov, NCT02927145.

Findings: The RH5.1/AS01_B 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.

Publication status:: Published

Peer review status:: Peer reviewed

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Cite

Cite this record

APA Style

Minassian, A. M., Silk, S. E., Barrett, J. R., Nielsen, C. M., Miura, K., Diouf, A., Loos, C., Fallon, J. K., Michell, A. R., White, M. T., Edwards, N. J., Poulton, I. D., Mitton, C. H., Payne, R. O., Marks, M., Maxwell-Scott, H., Querol-Rubiera, A., Bisnauthsing, K., Batra, R., … Draper, S. J. (2021). Reduced blood-stage malaria growth and immune correlates in humans following RH5 vaccination. Med, 2(6), 701–719.

MLA Style

Minassian, A. M., et al. “Reduced Blood-Stage Malaria Growth and Immune Correlates in Humans Following RH5 Vaccination.” Med, vol. 2, no. 6, Cell Press, 2021, pp. 701–19.

Chicago Style

Minassian, AM, SE Silk, JR Barrett, CM Nielsen, K Miura, A Diouf, C Loos, et al. 2021. “Reduced Blood-Stage Malaria Growth and Immune Correlates in Humans Following RH5 Vaccination.” Med 2 (6): 701–19.
Share
Print