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J Infect Dis. The Malaria Vaccine Candidate GMZ2 Elicits Functional Antibodies in Individuals From Malaria Endemic and Non-Endemic Areas
[Source: The Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]
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The Malaria Vaccine Candidate GMZ2 Elicits Functional Antibodies in Individuals From Malaria Endemic and Non-Endemic Areas
Micha Phill Gr?nholm Jepsen 1,2,3,a, Prajakta S. Jogdand 1,2,3,a, Susheel K. Singh 2,3, Meral Esen 4,5, Michael Christiansen 1, Saadou Issifou 4,5, Aurore B. Hounkpatin 4,5, Ulysse Ateba-Ngoa 5, Peter G. Kremsner 4,5, Morten H. Dziegiel 6, Severin Olesen-Larsen 1, S?ren Jepsen 1, Benjamin Mordm?ller 4,5 and Michael Theisen 1,2,3
Author Affiliations: <SUP>1</SUP>Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut <SUP>2</SUP>Centre for Medical Parasitology at Department of International Health, Immunology, and Microbiology, University of Copenhagen <SUP>3</SUP>Department of Infectious Diseases <SUP>6</SUP>Blood Bank, Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark <SUP>4</SUP>Institut f?r Tropenmedizin, Universit?t T?bingen, Germany <SUP>5</SUP>Centre de Recherches M?dicales de Lambar?n?, Lambaren?, Gabon
Correspondence: Michael Theisen, PhD, DSc, Department of Clinical Biochemistry and Immunology, Statens Serum Institute, ?restads Blvd 5, 2300 Copenhagen S, Denmark (mth@ssi.dk).
<CITE><ABBR>J Infect Dis.</ABBR> (2013) doi: 10.1093/infdis/jit185 </CITE>First published online: April 26, 2013
Abstract
Background.
GMZ2 is a hybrid protein consisting of the N-terminal region of the glutamate-rich protein fused in frame to the C-terminal region of merozoite surface protein 3 (MSP3). GMZ2 formulated in Al(OH)<SUB>3</SUB> has been tested in 3 published phase 1 clinical trials. The GMZ2/alum formulation showed good safety, tolerability, and immunogenicity, but whether antibodies elicited by vaccination are functional is not known.
Methods.
Serum samples prior to vaccination and 4 weeks after the last vaccination from the 3 clinical trials were used to perform a comparative assessment of biological activity against Plasmodium falciparum.
Results.
We showed that the maximum level of immunoglobulin G (IgG) antibodies obtained by GMZ2 vaccination is independent of ethnicity, time under malaria-exposure, and vaccine dose and that GMZ2 elicits high levels of functionally active IgG antibodies. Both, malaria-naive adults and malaria-exposed preschool children elicit vaccine-specific antibodies with broad inhibitory activity against geographically diverse P. falciparum isolates. Peptide-mapping studies of IgG subclass responses identified IgG3 against a peptide derived from MSP3 as the strongest predictor of antibody-dependent cellular inhibition.
Conclusions.
These findings suggest that GMZ2 adjuvanted in Al(OH)<SUB>3</SUB> elicits high levels of specific and functional antibodies with the capacity to control parasite multiplication.
Key words: GMZ2 ? GLURP ? MSP3 ? vaccine ? ADCI ? antibody ? immunity ? avidity - clinical trial - Plasmodium falciparum
Received December 21, 2012. Accepted February 7, 2013.
? The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
-Micha Phill Gr?nholm Jepsen 1,2,3,a, Prajakta S. Jogdand 1,2,3,a, Susheel K. Singh 2,3, Meral Esen 4,5, Michael Christiansen 1, Saadou Issifou 4,5, Aurore B. Hounkpatin 4,5, Ulysse Ateba-Ngoa 5, Peter G. Kremsner 4,5, Morten H. Dziegiel 6, Severin Olesen-Larsen 1, S?ren Jepsen 1, Benjamin Mordm?ller 4,5 and Michael Theisen 1,2,3
Author Affiliations: <SUP>1</SUP>Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut <SUP>2</SUP>Centre for Medical Parasitology at Department of International Health, Immunology, and Microbiology, University of Copenhagen <SUP>3</SUP>Department of Infectious Diseases <SUP>6</SUP>Blood Bank, Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark <SUP>4</SUP>Institut f?r Tropenmedizin, Universit?t T?bingen, Germany <SUP>5</SUP>Centre de Recherches M?dicales de Lambar?n?, Lambaren?, Gabon
Correspondence: Michael Theisen, PhD, DSc, Department of Clinical Biochemistry and Immunology, Statens Serum Institute, ?restads Blvd 5, 2300 Copenhagen S, Denmark (mth@ssi.dk).
<CITE><ABBR>J Infect Dis.</ABBR> (2013) doi: 10.1093/infdis/jit185 </CITE>First published online: April 26, 2013
Abstract
Background.
GMZ2 is a hybrid protein consisting of the N-terminal region of the glutamate-rich protein fused in frame to the C-terminal region of merozoite surface protein 3 (MSP3). GMZ2 formulated in Al(OH)<SUB>3</SUB> has been tested in 3 published phase 1 clinical trials. The GMZ2/alum formulation showed good safety, tolerability, and immunogenicity, but whether antibodies elicited by vaccination are functional is not known.
Methods.
Serum samples prior to vaccination and 4 weeks after the last vaccination from the 3 clinical trials were used to perform a comparative assessment of biological activity against Plasmodium falciparum.
Results.
We showed that the maximum level of immunoglobulin G (IgG) antibodies obtained by GMZ2 vaccination is independent of ethnicity, time under malaria-exposure, and vaccine dose and that GMZ2 elicits high levels of functionally active IgG antibodies. Both, malaria-naive adults and malaria-exposed preschool children elicit vaccine-specific antibodies with broad inhibitory activity against geographically diverse P. falciparum isolates. Peptide-mapping studies of IgG subclass responses identified IgG3 against a peptide derived from MSP3 as the strongest predictor of antibody-dependent cellular inhibition.
Conclusions.
These findings suggest that GMZ2 adjuvanted in Al(OH)<SUB>3</SUB> elicits high levels of specific and functional antibodies with the capacity to control parasite multiplication.
Key words: GMZ2 ? GLURP ? MSP3 ? vaccine ? ADCI ? antibody ? immunity ? avidity - clinical trial - Plasmodium falciparum
Received December 21, 2012. Accepted February 7, 2013.
? The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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