Journal
CLINICAL INFECTIOUS DISEASES
Volume 69, Issue 8, Pages 1377-1384Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cid/ciy1087
Keywords
clinical trial; Plasmodium falciparum; malaria vaccine; controlled human malaria infection
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Funding
- German Center for Infection Research [TTU 03.801, TTU 03.702, TTU 03.703]
- National Institute of Allergy and Infectious Diseases of the National Institutes of Health [5R44AI058375, 5R44AI055229]
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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 mu g GMZ2 formulated in CAF01, a liposome-based adjuvant; 100 mu g 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 (R) 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 mu g GMZ2-CAF01, and 5/11 100 mu g 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.
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