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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.

SUBMITTER: Dejon-Agobe JC 

PROVIDER: S-EPMC6763635 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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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.

Dejon-Agobe Jean Claude JC   Ateba-Ngoa Ulysse U   Lalremruata Albert A   Homoet Andreas A   Engelhorn Julie J   Nouatin Odilon Paterne OP   Edoa Jean Ronald JR   Fernandes José F JF   Esen Meral M   Mouwenda Yoanne Darelle YD   Betouke Ongwe Eunice M EM   Massinga-Loembe Marguerite M   Hoffman Stephen L SL   Sim B Kim Lee BKL   Theisen Michael M   Kremsner Peter G PG   Adegnika Ayôla A AA   Lell Bertrand B   Mordmüller Benjamin B  

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20190901 8


<h4>Background</h4>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.<h4>Methods</h4>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, fo  ...[more]

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