Solution structure of a <it>Plasmodium falciparum </it>AMA-1/MSP 1 chimeric protein vaccine candidate (PfCP-2.9) for malaria
<p>Abstract</p> <p>Background</p> <p>The <it>Plasmodium falciparum </it>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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-03-01
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| Series: | Malaria Journal |
| Online Access: | http://www.malariajournal.com/content/9/1/76 |
| Summary: | <p>Abstract</p> <p>Background</p> <p>The <it>Plasmodium falciparum </it>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 <it>in vitro</it>.</p> <p>Methods</p> <p>The <sup>15</sup>N-labeled and <sup>13</sup>C/<sup>15</sup>N-labeled PfCP-2.9 was produced in <it>Pichia pastoris </it>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 (<it>R</it><sub>2</sub>) of the PfMSP1-19 alone were compared with that of the PfCP-2.9.</p> <p>Results</p> <p>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 (<it>R</it><sub>2</sub>) strongly suggests no weak interaction between the domains.</p> <p>Conclusions</p> <p>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.</p> |
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| ISSN: | 1475-2875 |