Abstract
BackgroundGMZ2 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 naïve 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 FindingsThirty children one to five years of age were randomized to receive three doses of either 30 µg or 100 µg 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 µg and 100 µg 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 µg GMZ2 group than in the rabies vaccine controls, and 16-fold (7,36) higher in the 100 µg 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 µg group than in the rabies group and 3.8-fold (1.5,9.6) higher in the 100 µg group. Memory B-cells against GMZ2 developed in both GMZ2 vaccinated groups.Conclusions/SignificanceBoth 30 µg as well as 100 µg intramuscular GMZ2 are immunogenic, well tolerated, and safe in young, malaria-exposed Gabonese children. This result confirms previous findings in naïve and malaria-exposed adults and supports further clinical development of GMZ2.Trial RegistrationClinicalTrials.gov NCT00703066
Highlights
Malaria control relies primarily on case management and the use of impregnated bednets
High antiGLURP titers have been associated with protection from malaria in several studies [8,9] and it was shown that anti-glutamate rich protein (GLURP) antibodies induce antibody-dependent cellular inhibition (ADCI) in a way similar to merozoite surface protein 3 (MSP3) [10]
Since the presumed mechanism of protection of MSP3 and GLURP is similar, and partial protection in pre-clinical trials was documented [11], it was decided to develop a MSP3-GLURP fusion protein for studies in humans naturally exposed to malaria
Summary
Malaria control relies primarily on case management and the use of impregnated bednets. Analysis of sera from immune adults from endemic regions, including those from passive transfer experiments, led to the identification of merozoite surface protein 3 (MSP3) as a potentially important antigen for the induction of anti-malarial immunity [7]. Another antigen that elicits antibodies in frequently exposed individuals is glutamate rich protein (GLURP). Since the presumed mechanism of protection of MSP3 and GLURP is similar, and partial protection in pre-clinical trials was documented [11], it was decided to develop a MSP3-GLURP fusion protein for studies in humans naturally exposed to malaria. 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
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