Solution structure of a Plasmodium falciparum AMA-1/MSP 1 chimeric protein vaccine candidate (PfCP-2.9) for malaria

• Published in: Malaria Journal
• Main Authors: Jin Changwen, Zhou Aiguo, Hu Yunfei, Peng Heng, Pan Weiqing
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2010
• Subjects: Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/1475-2875-9-76; https://doaj.org/article/0d2ef6a580af4c9c91fcbb17546fe21d

Abstract Background The Plasmodium falciparum chimeric protein PfCP-2.9 is a promising asexual-stage malaria vaccine evaluated in clinical trials. This chimeric protein consists of two cysteine-rich domains: domain III of the apical membrane antigen 1 (AMA-1 [III]) and the C-terminal region of the merozoite surface protein 1 (MSP1-19). It has been reported that the fusion of these two antigens enhanced their immunogenicity and antibody-mediated inhibition of parasite growth in vitro . Methods The 15 N-labeled and 13 C/ 15 N-labeled PfCP-2.9 was produced in Pichia pastoris for nuclear magnetic resonance (NMR) structure analysis. The chemical shift assignments of PfCP-2.9 were compared with those previously reported for the individual domains (i.e., PfAMA-1(III) or PfMSP 1-19). The two-dimensional spectra and transverse relaxation rates ( R 2 ) of the PfMSP1-19 alone were compared with that of the PfCP-2.9. Results Confident backbone assignments were obtained for 122 out of 241 residues of PfCP-2.9. The assigned residues in PfCP-2.9 were very similar to those previously reported for the individual domains. The conformation of the PfMSP1-19 in different constructs is essentially the same. Comparison of transverse relaxation rates ( R 2 ) strongly suggests no weak interaction between the domains. Conclusions These data indicate that the fusion of AMA-1(III) and MSP1-19 as chimeric protein did not change their structures, supporting the use of the chimeric protein as a potential malaria vaccine.