Reduced blood-stage malaria growth and immune correlates in humans following RH5 vaccination.
Med
; 2(6): 701-719.e19, 2021 06 11.
Article
in En
| MEDLINE
| ID: mdl-34223402
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 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 â¼2 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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Malaria, Falciparum
/
Malaria Vaccines
/
Malaria
Type of study:
Clinical_trials
/
Prognostic_studies
Limits:
Adult
/
Humans
Language:
En
Journal:
Med
Year:
2021
Document type:
Article
Affiliation country:
United kingdom