A phase 2b randomized,controlled trial of the efficacy of the GMZ2 malaria vaccine in African children |
| |
| Affiliation: | 10. Centre National de Recherche et de Formation sur le Paludisme, Burkina Faso;11. Institute of Tropical Medicine, University of Tübingen, Germany;12. Centre de Recherches Médicales de Lambaréné (CERMEL), Gabon;13. Makerere University College of Health Sciences, Uganda;14. Navrongo Health Research Centre, Ghana;15. Medical Research Council, Fajara, Gambia;p. Statens Serum Institut, Denmark;q. Harvard School of Public Health Research Collaboration, Boston, USA;1. Centre National de Recherche et de Formation sur le Paludisme, Burkina Faso;2. Institute of Tropical Medicine, University of Tübingen, Germany;3. London School of Hygiene & Tropical Medicine, UK;4. Centre de Recherches Médicales de Lambaréné (CERMEL), Gabon;5. Makerere University College of Health Sciences, Uganda;6. Navrongo Health Research Centre, Ghana;7. Statens Serum Institut, Denmark;8. Centre for Infectious Disease Research in Zambia, Zambia;9. 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;1. Barcelona Centre for International Health Research CRESIB, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain;2. Centro de Investigaçao em Saúde de Manhiça (CISM), Manhiça, Mozambique;3. Faculdade de Medicina, Universidade Eduardo Mondlane, Maputo, Mozambique;4. Instituto Nacional de Saúde, Ministério de Saúde, Maputo, Mozambique;1. Infectious Disease Research Institute, 1616 Eastlake Ave. E., Suite 400, Seattle, WA 98102, USA;2. Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands;3. Department for Congenital Disorders, Statens Serum Institute, Copenhagen, Denmark;4. Centre for Medical Parasitology at Department of International Health, Immunology and Microbiology, University of Copenhagen, Denmark;1. Medical Research Council Unit, Fajara, The Gambia;2. Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso;3. The Jenner Institute Laboratories, University of Oxford, Oxford, UK;4. Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, Churchill Hospital, Oxford, UK;5. Keires AG, Bäumleingasse, Basel, Switzerland;6. ReiThera, Rome, Italy;7. CEINGE, Naples, Italy;8. Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy;9. European Vaccine Initiative, UniversitätsKlinikum Heidelberg, Heidelberg, Germany;10. Current address: Department of Immunology, Monash University, Prahran, Melbourne, Australia;11. Kenya Medical Research Institute, Centre for Geographical Medical Research (Coast), Kilifi, Kenya;1. Sanaria Inc., Rockville, MD 20850, USA;2. GSK Vaccines, Rixensart, Belgium;3. Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA;1. Malaria Research and Training Center, Mali National Institute of Allergy and Infectious Diseases International Centers for Excellence in Research, University of Science, Techniques and Technologies of Bamako, Bamako, Mali;2. Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA;3. Biostatistical Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA;4. Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA;5. Sanaria, Rockville, MD, USA;1. Jenner Institute, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford OX3 7DQ, UK;2. Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Old Road, Headington, Oxford OX3 7LJ, United Kingdom;3. Novavax AB, Kungsgatan 109, SE-753 18 Uppsala, Sweden |
| |
| Abstract: | BackgroundGMZ2 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.MethodsChildren 12–60 months old were randomized to receive three injections of either 100 μg 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.ResultsA 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%).ConclusionsGMZ2 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. |
| |
| Keywords: | Phase 2 clinical trial GMZ2 GLURP MSP3 Vaccine Antibody Efficacy |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
