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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

Research output: Contribution to journalJournal articleResearchpeer-review


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  • 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
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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 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.

Original languageEnglish
JournalClinical infectious diseases : an official publication of the Infectious Diseases Society of America
Issue number8
Pages (from-to)1377-1384
Number of pages8
Publication statusPublished - 27 Sep 2019

ID: 59239456