A randomized controlled Phase Ib trial of the malaria vaccine candidate GMZ2 in African children

Sabine Bélard; Saadou Issifou; Aurore B Hounkpatin; Frieder Schaumburg; Ulysse Ateba Ngoa; Meral Esen; Rolf Fendel; Pablo Martinez de Salazar; Raymund E Mürbeth; Paul Milligan; Nathalie Imbault; Egeruan Babatunde Imoukhuede; Michael Theisen; Søren Jepsen; Ramadhani A Noor; Brenda Okech; Peter G Kremsner; Benjamin Mordmüller

doi:10.1371/journal.pone.0022525

A randomized controlled Phase Ib trial of the malaria vaccine candidate GMZ2 in African children

Sabine Bélard, Saadou Issifou, Aurore B Hounkpatin, Frieder Schaumburg, Ulysse Ateba Ngoa, Meral Esen, Rolf Fendel, Pablo Martinez de Salazar, Raymund E Mürbeth, Paul Milligan, Nathalie Imbault, Egeruan Babatunde Imoukhuede, Michael Theisen, Søren Jepsen, Ramadhani A Noor, Brenda Okech, Peter G Kremsner, Benjamin Mordmüller

48 Citations (Scopus)

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 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 Findings: Thirty 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/Significance: Both 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.

Original language	English
Journal	P L o S One
Volume	6
Issue number	7
Pages (from-to)	e22525
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0022525
Publication status	Published - 2011

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Bélard, S., Issifou, S., Hounkpatin, A. B., Schaumburg, F., Ngoa, U. A., Esen, M., Fendel, R., de Salazar, P. M., Mürbeth, R. E., Milligan, P., Imbault, N., Imoukhuede, E. B., Theisen, M., Jepsen, S., Noor, R. A., Okech, B., Kremsner, P. G., & Mordmüller, B. (2011). A randomized controlled Phase Ib trial of the malaria vaccine candidate GMZ2 in African children. P L o S One, 6(7), e22525. https://doi.org/10.1371/journal.pone.0022525

Bélard, S, Issifou, S, Hounkpatin, AB, Schaumburg, F, Ngoa, UA, Esen, M, Fendel, R, de Salazar, PM, Mürbeth, RE, Milligan, P, Imbault, N, Imoukhuede, EB, Theisen, M, Jepsen, S, Noor, RA, Okech, B, Kremsner, PG & Mordmüller, B 2011, 'A randomized controlled Phase Ib trial of the malaria vaccine candidate GMZ2 in African children', P L o S One, vol. 6, no. 7, pp. e22525. https://doi.org/10.1371/journal.pone.0022525

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title = "A randomized controlled Phase Ib trial of the malaria vaccine candidate GMZ2 in African children",

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 na{\"i}ve 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 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/Significance: Both 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 na{\"i}ve and malaria-exposed adults and supports further clinical development of GMZ2.",

author = "Sabine B{\'e}lard and Saadou Issifou and Hounkpatin, {Aurore B} and Frieder Schaumburg and Ngoa, {Ulysse Ateba} and Meral Esen and Rolf Fendel and {de Salazar}, {Pablo Martinez} and M{\"u}rbeth, {Raymund E} and Paul Milligan and Nathalie Imbault and Imoukhuede, {Egeruan Babatunde} and Michael Theisen and S{\o}ren Jepsen and Noor, {Ramadhani A} and Brenda Okech and Kremsner, {Peter G} and Benjamin Mordm{\"u}ller",

year = "2011",

doi = "10.1371/journal.pone.0022525",

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T1 - A randomized controlled Phase Ib trial of the malaria vaccine candidate GMZ2 in African children

AU - Bélard, Sabine

AU - Issifou, Saadou

AU - Hounkpatin, Aurore B

AU - Schaumburg, Frieder

AU - Ngoa, Ulysse Ateba

AU - Esen, Meral

AU - Fendel, Rolf

AU - de Salazar, Pablo Martinez

AU - Mürbeth, Raymund E

AU - Milligan, Paul

AU - Imbault, Nathalie

AU - Imoukhuede, Egeruan Babatunde

AU - Theisen, Michael

AU - Jepsen, Søren

AU - Noor, Ramadhani A

AU - Okech, Brenda

AU - Kremsner, Peter G

AU - Mordmüller, Benjamin

PY - 2011

Y1 - 2011

N2 - 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 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 Findings: Thirty 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/Significance: Both 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.

AB - 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 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 Findings: Thirty 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/Significance: Both 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.

U2 - 10.1371/journal.pone.0022525

DO - 10.1371/journal.pone.0022525

M3 - Journal article

C2 - 21829466

SN - 1932-6203

VL - 6

SP - e22525

JO - P L o S One

JF - P L o S One

IS - 7

ER -

A randomized controlled Phase Ib trial of the malaria vaccine candidate GMZ2 in African children

Abstract

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