Journal Article

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

Kaddumukasa, Mark, Asoala, Victor, Bangre, Oscar, Honkpehedji, Yabo Josiane, Hounkpatin, Aurore B., Kironde, Fred, Nébié, Issa, Sirima, Sodiomon B., Débé, Siaka, Diarra, Amidou, Anyorigiya, Thomas, Christiansen, Michael, Ansah, Nana Akosua, Atuguba, Frank, Buwembo, William, Issifou, Saadou, Abubakar, Ismaela, Chilengi, Roma, Bougouma, Edith, Ouédraogo, Alphonse, Theisen, Michael, Ajua, Anthony, Milligan, Paul, Joanny, Fanny, Esen, Meral, Mworozi, Edison, Ngoa, Ulysse Ateba, Kargougou, Désiré, Kremsner, Peter G., Bang, Peter, Jepsen, Søren, Lell, Bertrand, Mordmüller, Benjamin, Tiono, Alfred B., Ejigu, Dawit A., Flach, Clare, Bojang, Kalifa, Noor, Ramadhani, Adegnika, Ayola Akim, Sekikubo, Musa, Okech, Brenda, Agobe, Jean Claude Dejon

2016

Overview

•The GMZ2 fusion protein consist of the non-repeat region of falciparum GLURP genetically fused to a msp3 fragment.•The GMZ2 fusion protein elicited functional antibodies in phase 1 studies.•In the ATP analysis, vaccine efficacy adjusted for age and site was 14% (95% CI: 3.6%, 23%).•Vaccine efficacy was higher in older children.•In GMZ2-vaccinated children, the incidence of malaria decreased with increasing vaccine-induced anti-GMZ2 IgG concentration. 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. 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. 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%). 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.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Adjuvants, Immunologic - administration & dosage / Africans / Age / Allergy and Immunology / Aluminum / aluminum hydroxide / Aluminum Hydroxide - administration & dosage / Antibodies, Protozoan - blood / Antibody / Antigens / Antigens, Protozoan - immunology / Blood / Burkina Faso / Child, Preschool / children / Children & youth / Clinical trials / confidence interval / Efficacy / Female / Fever / Gabon / Ghana / GLURP / GMZ2 / Humans / immunoglobulin G / Immunoglobulin G - blood / Immunoglobulins / Infant / Malaria / malaria vaccines / Malaria Vaccines - immunology / Malaria, Falciparum - prevention & control / Male / merozoites / MSP3 / Parasites / Phase 2 clinical trial / Plasmodium falciparum / Proteins / Protozoan Proteins - immunology / Public health / rabies / Recombinant Fusion Proteins - immunology / recombinant proteins / surface proteins / Tropical diseases / Uganda / Vaccine / Vaccines / Vector-borne diseases