Controlled Human Malaria Infection of Healthy Adults With Lifelong Malaria Exposure to Assess Safety, Immunogenicity, and Efficacy of the Asexual Blood Stage Malaria Vaccine Candidate GMZ2

GMZ2 is a recombinant malaria vaccine inducing immune responses against Plasmodium falciparum (Pf) merozoite surface protein-3 and glutamate-rich protein. We used standardized controlled human malaria infection (CHMI) to assess the efficacy of this asexual blood-stage vaccine. We vaccinated 50 healt...

Full description

Saved in:

Bibliographic Details
Published in:	Clinical infectious diseases Vol. 69; no. 8; pp. 1377 - 1384
Main Authors:	Dejon-Agobe, Jean Claude, Ateba-Ngoa, Ulysse, Lalremruata, Albert, Homoet, Andreas, Engelhorn, Julie, Nouatin, Odilon Paterne, Edoa, Jean Ronald, Fernandes, José F, Esen, Meral, Mouwenda, Yoanne Darelle, Betouke Ongwe, Eunice M, Massinga-Loembe, Marguerite, Hoffman, Stephen L, Sim, B Kim Lee, Theisen, Michael, Kremsner, Peter G, Adegnika, Ayôla A, Lell, Bertrand, Mordmüller, Benjamin
Format:	Journal Article
Language:	English
Published:	United States Oxford University Press 27-09-2019
Subjects:	Adjuvants, Immunologic Adolescent Adult and Commentaries Antigens, Protozoan - immunology Double-Blind Method Humans Malaria Vaccines - immunology Malaria, Falciparum - parasitology Malaria, Falciparum - prevention & control Parasitemia Plasmodium falciparum - immunology Protozoan Proteins - immunology Sporozoites Vaccination Vaccines, Synthetic - immunology Young Adult clinical trial Plasmodium falciparum malaria vaccine controlled human malaria infection
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	GMZ2 is a recombinant malaria vaccine inducing immune responses against Plasmodium falciparum (Pf) merozoite surface protein-3 and glutamate-rich protein. We used standardized controlled human malaria infection (CHMI) to assess the efficacy of this asexual blood-stage vaccine. We vaccinated 50 healthy, adult volunteers with lifelong exposure to Pf 3 times, at 4-week intervals, with 30 or 100 µg GMZ2 formulated in CAF01, a liposome-based adjuvant; 100 µg GMZ2, formulated in Alhydrogel; or a control vaccine (Verorab). Approximately 13 weeks after the last vaccination, 35/50 volunteers underwent CHMI by direct venous inoculation of 3200 Pf sporozoites (Sanaria® PfSPZ Challenge). Adverse events were similarly distributed between GMZ2 and control vaccinees. Baseline-corrected anti-GMZ2 antibody concentrations 4 weeks after the last vaccination were higher in all 3 GMZ2-vaccinated arms, compared to the control group. All GMZ2 formulations induced similar antibody levels. CHMI resulted in 29/34 (85%) volunteers with Pf parasitemia and 15/34 (44%) with malaria (parasitemia and symptoms). The proportion of participants with malaria (2/5 control, 6/10 GMZ2-Alhydrogel, 2/8 30 µg GMZ2-CAF01, and 5/11 100 µg GMZ2-CAF01) and the time it took them to develop malaria were similar in all groups. Baseline, vaccine-specific antibody concentrations were associated with protection against malaria. GMZ2 is well tolerated and immunogenic in lifelong-Pf-exposed adults from Gabon, with similar antibody responses regardless of formulation. CHMI showed no protective effect of prior vaccination with GMZ2, although baseline, vaccine-specific antibody concentrations were associated with protection. CHMI with the PfSPZ Challenge is a potent new tool to validate asexual, blood-stage malaria vaccines in Africa. Pan-African Clinical Trials: PACTR201503001038304.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3 J. C. D.-A. and U. A.-N. contributed equally to this manuscript.
ISSN:	1058-4838 1537-6591 1537-6591
DOI:	10.1093/cid/ciy1087