A Randomized Controlled Phase Ib Trial of the Malaria Vaccine Candidate GMZ2 in African Children


Belard, S; Issifou, S; Hounkpatin, AB; Schaumburg, F; Ngoa, UA; Esen, M; Fendel, R; de Salazar, PM; Murbeth, RE; Milligan, P; Imbault, N; Imoukhuede, EB; Theisen, M; Jepsen, S; Noor, RA; Okech, B; Kremsner, PG; Mordmuller, B; (2011) A Randomized Controlled Phase Ib Trial of the Malaria Vaccine Candidate GMZ2 in African Children. PLoS One, 6 (7). ISSN 1932-6203 DOI: 10.1371/journal.pone.0022525

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Abstract

Background: GMZ2 is a fusion protein of Plasmodium falciparum merozoite surface protein 3 (MSP3) and glutamate rich protein (GLURP) that mediates an immune response against the blood stage of the parasite. Two previous phase I clinical trials, one in naive European adults and one in malaria-exposed Gabonese adults showed that GMZ2 was well tolerated and immunogenic. Here, we present data on safety and immunogenicity of GMZ2 in one to five year old Gabonese children, a target population for future malaria vaccine efficacy trials Methodology/Principal Findings: Thirty children one to five years of age were randomized to receive three doses of either 30 mu g or 100 mu g of GMZ2, or rabies vaccine. GMZ2, adjuvanted in aluminum hydroxide, was administered on Days 0, 28 and 56. All participants received a full course of their respective vaccination and were followed up for one year. Both 30 mu g and 100 mu g GMZ2 vaccine doses were well tolerated and induced antibodies and memory B-cells against GMZ2 as well as its antigenic constituents MSP3 and GLURP. After three doses of vaccine, the geometric mean concentration of antibodies to GMZ2 was 19-fold (95% CI: 11,34) higher in the 30 mu g GMZ2 group than in the rabies vaccine controls, and 16-fold (7,36) higher in the 100 mu g GMZ2 group than the rabies group. Geometric mean concentration of antibodies to MSP3 was 2.7-fold (1.6,4.6) higher in the 30 mu g group than in the rabies group and 3.8-fold (1.5,9.6) higher in the 100 mu g group. Memory B-cells against GMZ2 developed in both GMZ2 vaccinated groups. Conclusions/Significance: Both 30 mu g as well as 100 mu g intramuscular GMZ2 are immunogenic, well tolerated, and safe in young, malaria-exposed Gabonese children. This result confirms previous findings in naive and malaria-exposed adults and supports further clinical development of GMZ2.

Item Type: Article
Keywords: glutamate-rich protein, merozoite surface protein-3, plasmodium-falciparum, protection, antibodies, glurp, immunization, association, safety, gabon
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Research Centre: Tropical Epidemiology Group
Vaccine Centre
PubMed ID: 21829466
Web of Science ID: 293284600017
URI: http://researchonline.lshtm.ac.uk/id/eprint/282

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