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.

Abstract

BACKGROUND:

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.

METHODS:

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).

RESULTS:

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.

CONCLUSIONS:

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.

CLINICAL TRIALS REGISTRATION:

Pan-African Clinical Trials: PACTR201503001038304.

• Authors: Jean Claude Dejon-Agobe, Ulysse Ateba-Ngoa, Albert Lalremruata, Andreas Homoet, Julie Engelhorn, Odilon Paterne Nouatin, Jean Ronald Edoa, José F Fernandes, Meral Esen, Yoanne Darelle Mouwenda, Eunice M Betouke Ongwe, Marguerite Massinga-Loembe, Stephen L Hoffman, B Kim Lee Sim, Michael Theisen, Peter G Kremsner, Ayôla A Adegnika, Bertrand Lell, Benjamin Mordmüller
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 69 Issue 8 Pg. 1377-1384 (09 27 2019) ISSN: 1537-6591 [Electronic] United States
• PMID: 30561539 (Publication Type: Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

Chemical References

• Adjuvants, Immunologic
• Antigens, Protozoan
• GMZ2 vaccine
• Malaria Vaccines
• Protozoan Proteins
• Vaccines, Synthetic
• merozoite surface protein 3, Plasmodium

Topics

• Adjuvants, Immunologic
• Adolescent
• Adult
• Antigens, Protozoan (immunology)
• Double-Blind Method
• Humans
• Malaria Vaccines (immunology)
• Malaria, Falciparum (parasitology, prevention & control)
• Parasitemia
• Plasmodium falciparum (immunology)
• Protozoan Proteins (immunology)
• Sporozoites
• Vaccination
• Vaccines, Synthetic (immunology)
• Young Adult