Browsing by Author "Milligan P"

Filter results by typing the first few letters
Now showing 1 - 1 of 1
  • Thumbnail Image
    Item
    A phase 2b randomized, controlled trial of the efficacy of the GMZ2 malaria vaccine in African children.
    (2016-Aug-31) Sirima SB; Mordmüller B; Milligan P; Ngoa UA; Kironde F; Atuguba F; Tiono AB; Issifou S; Kaddumukasa M; Bangre O; Flach C; Christiansen M; Bang P; Chilengi R; Jepsen S; Kremsner PG; Theisen M; Centre for Infectious Disease Research in Zambia, Zambia.; Statens Serum Institut, Denmark; Centre for Medical Parasitology at Department of International Health, Immunology, and Microbiology, University of Copenhagen, and Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Denmark. Electronic address: mth@ssi.dk.; Makerere University College of Health Sciences, Uganda.; London School of Hygiene & Tropical Medicine, UK.; Navrongo Health Research Centre, Ghana.; Statens Serum Institut, Denmark.; Institute of Tropical Medicine, University of Tübingen, Germany; Centre de Recherches Médicales de Lambaréné (CERMEL), Gabon.; Institute of Tropical Medicine, University of Tübingen, Germany.; Centre National de Recherche et de Formation sur le Paludisme, Burkina Faso.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    BACKGROUND: GMZ2 is a recombinant protein malaria vaccine, comprising two blood-stage antigens of Plasmodium falciparum, glutamate-rich protein and merozoite surface protein 3. We assessed efficacy of GMZ2 in children in Burkina Faso, Gabon, Ghana and Uganda. METHODS: Children 12-60months old were randomized to receive three injections of either 100μg GMZ2 adjuvanted with aluminum hydroxide or a control vaccine (rabies) four weeks apart and were followed up for six months to measure the incidence of malaria defined as fever or history of fever and a parasite density ⩾5000/μL. RESULTS: A cohort of 1849 children were randomized, 1735 received three doses of vaccine (868 GMZ2, 867 control-vaccine). There were 641 malaria episodes in the GMZ2/Alum group and 720 in the control group. In the ATP analysis, vaccine efficacy (VE), adjusted for age and site was 14% (95% confidence interval [CI]: 3.6%, 23%, p-value=0.009). In the ITT analysis, age-adjusted VE was 11.3% (95% CI 2.5%, 19%, p-value=0.013). VE was higher in older children. In GMZ2-vaccinated children, the incidence of malaria decreased with increasing vaccine-induced anti-GMZ2 IgG concentration. There were 32 cases of severe malaria (18 in the rabies vaccine group and 14 in the GMZ2 group), VE 27% (95% CI -44%, 63%). CONCLUSIONS: GMZ2 is the first blood-stage malaria vaccine to be evaluated in a large multicenter trial. GMZ2 was well tolerated and immunogenic, and reduced the incidence of malaria, but efficacy would need to be substantially improved, using a more immunogenic formulation, for the vaccine to have a public health role.