A phase 2b randomized, controlled trial of the efficacy of the GMZ2 malaria vaccine in African children.

Abstract

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.

• Authors: Sodiomon B Sirima, Benjamin Mordmüller, Paul Milligan, Ulysse Ateba Ngoa, Fred Kironde, Frank Atuguba, Alfred B Tiono, Saadou Issifou, Mark Kaddumukasa, Oscar Bangre, Clare Flach, Michael Christiansen, Peter Bang, Roma Chilengi, Søren Jepsen, Peter G Kremsner, Michael Theisen, GMZ2 Trial Study Group
• Journal: Vaccine (Vaccine) Vol. 34 Issue 38 Pg. 4536-4542 (08 31 2016) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 27477844 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical References

• Adjuvants, Immunologic
• Antibodies, Protozoan
• Antigens, Protozoan
• GMZ2 vaccine
• Immunoglobulin G
• Malaria Vaccines
• Protozoan Proteins
• Recombinant Fusion Proteins
• merozoite surface protein 3, Plasmodium
• glutamate-rich protein, Plasmodium
• Aluminum Hydroxide

Topics

• Adjuvants, Immunologic (administration & dosage)
• Aluminum Hydroxide (administration & dosage)
• Antibodies, Protozoan (blood)
• Antigens, Protozoan (immunology)
• Burkina Faso
• Child, Preschool
• Female
• Gabon
• Ghana
• Humans
• Immunoglobulin G (blood)
• Infant
• Malaria Vaccines (immunology)
• Malaria, Falciparum (prevention & control)
• Male
• Plasmodium falciparum
• Protozoan Proteins (immunology)
• Recombinant Fusion Proteins (immunology)
• Uganda