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  • Title: The malaria vaccine candidate GMZ2 elicits functional antibodies in individuals from malaria endemic and non-endemic areas.
    Author: Jepsen MP, Jogdand PS, Singh SK, Esen M, Christiansen M, Issifou S, Hounkpatin AB, Ateba-Ngoa U, Kremsner PG, Dziegiel MH, Olesen-Larsen S, Jepsen S, Mordmüller B, Theisen M.
    Journal: J Infect Dis; 2013 Aug 01; 208(3):479-88. PubMed ID: 23624363.
    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)3 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)3 elicits high levels of specific and functional antibodies with the capacity to control parasite multiplication.
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