1. 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.
- Author
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Dejon-Agobe JC, Ateba-Ngoa U, Lalremruata A, Homoet A, Engelhorn J, Nouatin OP, Edoa JR, Fernandes JF, Esen M, Mouwenda YD, Betouke Ongwe EM, Massinga-Loembe M, Hoffman SL, Sim BKL, Theisen M, Kremsner PG, Adegnika AA, Lell B, and Mordmüller B
- Subjects
- Adjuvants, Immunologic, Adolescent, Adult, Double-Blind Method, Humans, Malaria, Falciparum parasitology, Parasitemia, Sporozoites, Vaccines, Synthetic immunology, Young Adult, Antigens, Protozoan immunology, Malaria Vaccines immunology, Malaria, Falciparum prevention & control, Plasmodium falciparum immunology, Protozoan Proteins immunology, Vaccination
- 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., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2019
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