期刊
JOURNAL OF INFECTIOUS DISEASES
卷 208, 期 3, 页码 479-488出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jit185
关键词
GMZ2; GLURP; MSP3; vaccine; ADCI; antibody; immunity; avidity; clinical trial; Plasmodium falciparum
资金
- European and Developing Countries Clinical Trials Partnership (EDCTP) [IP.2007.3110.001]
- German Federal Ministry of Education and Research (BMBF) [01KA0804]
- European Malaria Vaccine Initiative (EMVI)
- European Malaria Vaccine Development Association (EMVDA) of the European Union [LSHP-CT-2007-037506]
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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