Cargando…
A Randomized Controlled Phase Ib Trial of the Malaria Vaccine Candidate GMZ2 in African Children
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...
Autores principales: | , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145647/ https://www.ncbi.nlm.nih.gov/pubmed/21829466 http://dx.doi.org/10.1371/journal.pone.0022525 |
_version_ | 1782209113961267200 |
---|---|
author | Bélard, Sabine Issifou, Saadou Hounkpatin, Aurore B. Schaumburg, Frieder Ngoa, Ulysse Ateba Esen, Meral Fendel, Rolf de Salazar, Pablo Martinez Mürbeth, Raymund E. Milligan, Paul Imbault, Nathalie Imoukhuede, Egeruan Babatunde Theisen, Michael Jepsen, Søren Noor, Ramadhani A. Okech, Brenda Kremsner, Peter G. Mordmüller, Benjamin |
author_facet | Bélard, Sabine Issifou, Saadou Hounkpatin, Aurore B. Schaumburg, Frieder Ngoa, Ulysse Ateba Esen, Meral Fendel, Rolf de Salazar, Pablo Martinez Mürbeth, Raymund E. Milligan, Paul Imbault, Nathalie Imoukhuede, Egeruan Babatunde Theisen, Michael Jepsen, Søren Noor, Ramadhani A. Okech, Brenda Kremsner, Peter G. Mordmüller, Benjamin |
author_sort | Bélard, Sabine |
collection | PubMed |
description | 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT00703066 |
format | Online Article Text |
id | pubmed-3145647 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31456472011-08-09 A Randomized Controlled Phase Ib Trial of the Malaria Vaccine Candidate GMZ2 in African Children Bélard, Sabine Issifou, Saadou Hounkpatin, Aurore B. Schaumburg, Frieder Ngoa, Ulysse Ateba Esen, Meral Fendel, Rolf de Salazar, Pablo Martinez Mürbeth, Raymund E. Milligan, Paul Imbault, Nathalie Imoukhuede, Egeruan Babatunde Theisen, Michael Jepsen, Søren Noor, Ramadhani A. Okech, Brenda Kremsner, Peter G. Mordmüller, Benjamin PLoS One Research Article 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT00703066 Public Library of Science 2011-07-28 /pmc/articles/PMC3145647/ /pubmed/21829466 http://dx.doi.org/10.1371/journal.pone.0022525 Text en Bélard et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Bélard, Sabine Issifou, Saadou Hounkpatin, Aurore B. Schaumburg, Frieder Ngoa, Ulysse Ateba Esen, Meral Fendel, Rolf de Salazar, Pablo Martinez Mürbeth, Raymund E. Milligan, Paul Imbault, Nathalie Imoukhuede, Egeruan Babatunde Theisen, Michael Jepsen, Søren Noor, Ramadhani A. Okech, Brenda Kremsner, Peter G. Mordmüller, Benjamin A Randomized Controlled Phase Ib Trial of the Malaria Vaccine Candidate GMZ2 in African Children |
title | A Randomized Controlled Phase Ib Trial of the Malaria Vaccine Candidate GMZ2 in African Children |
title_full | A Randomized Controlled Phase Ib Trial of the Malaria Vaccine Candidate GMZ2 in African Children |
title_fullStr | A Randomized Controlled Phase Ib Trial of the Malaria Vaccine Candidate GMZ2 in African Children |
title_full_unstemmed | A Randomized Controlled Phase Ib Trial of the Malaria Vaccine Candidate GMZ2 in African Children |
title_short | A Randomized Controlled Phase Ib Trial of the Malaria Vaccine Candidate GMZ2 in African Children |
title_sort | randomized controlled phase ib trial of the malaria vaccine candidate gmz2 in african children |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145647/ https://www.ncbi.nlm.nih.gov/pubmed/21829466 http://dx.doi.org/10.1371/journal.pone.0022525 |
work_keys_str_mv | AT belardsabine arandomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT issifousaadou arandomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT hounkpatinauroreb arandomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT schaumburgfrieder arandomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT ngoaulysseateba arandomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT esenmeral arandomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT fendelrolf arandomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT desalazarpablomartinez arandomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT murbethraymunde arandomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT milliganpaul arandomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT imbaultnathalie arandomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT imoukhuedeegeruanbabatunde arandomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT theisenmichael arandomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT jepsensøren arandomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT noorramadhania arandomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT okechbrenda arandomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT kremsnerpeterg arandomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT mordmullerbenjamin arandomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT belardsabine randomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT issifousaadou randomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT hounkpatinauroreb randomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT schaumburgfrieder randomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT ngoaulysseateba randomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT esenmeral randomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT fendelrolf randomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT desalazarpablomartinez randomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT murbethraymunde randomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT milliganpaul randomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT imbaultnathalie randomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT imoukhuedeegeruanbabatunde randomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT theisenmichael randomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT jepsensøren randomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT noorramadhania randomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT okechbrenda randomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT kremsnerpeterg randomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren AT mordmullerbenjamin randomizedcontrolledphaseibtrialofthemalariavaccinecandidategmz2inafricanchildren |