- Introduction
- Materials and Methods
- Results
- Geographical origin of Colombian isolates.
- Nucleotide diversity.
- Synonymous and non-synonymous substitutions.
- Non-synonymous substitutions in conserved blocks of Colombian isolates.
- Variable blocks classification in Colombian isolates.
- Allelic distribution.
- Phylogenetic analysis.
- Epitope conservation analysis.
- Discussion
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Polymorphism of the Pv200L Fragment of Merozoite Surface Protein-1 of Plasmodium vivax in Clinical Isolates from the Pacific Coast of Colombia
Merozoite surface protein 1 (MSP-1) is a polymorphic malaria protein with functional domains involved in parasite erythrocyte interaction. Plasmodium vivax MSP-1 has a fragment (Pv200L) that has been identified as a potential subunit vaccine because it is highly immunogenic and induces partial protection against infectious parasite challenge in vaccinated monkeys. To determine the extent of genetic polymorphism and its effect on the translated protein, we sequenced the Pv200L coding region from isolates of 26 P. vivax-infected patients in a malaria-endemic area of Colombia. The extent of nucleotide diversity (π) in these isolates (0.061 ± 0.004) was significantly lower (P ≤ 0.001) than that observed in Thai and Brazilian isolates; 0.083 ± 0.006 and 0.090 ± 0.006, respectively. We found two new alleles and several previously unidentified dimorphic substitutions and significant size polymorphism. The presence of highly conserved blocks in this fragment has important implications for the development of Pv200L as a subunit vaccine candidate.
Author Notes
Financial support: This study was supported through a P. vivax vaccine research program granted by the National Institute of Allergy and Infectious Diseases (NIAID grant no. A1-49486/ TMRC), National Bureau of Sciences, University of Valle State (contract no. 245-2004), COLCIENCIAS (grant 1106-04-16489), and the Colombian Ministry of Social Protection (grant 2304-04-19524) (contract no.253-2005). Ananías A. Escalante is supported by the grant R01GM080586 from the National Institutes of Health, USA and through an International Center of Excellence for Malaria Research NIAID/ICEMR grant no U 19AI089702.
Authors' addresses: Augusto Valderrama-Aguirre, Evelin Zúñiga-Soto, Luz Ángela Moreno, Myriam Arévalo-Herrera, and Sócrates Herrera, Instituto de Inmunología, Facultad de Salud, Universidad del Valle, Cali, Colombia and Malaria Vaccine and Drug Development Center, Cali, Colombia, E-mails: avalderrama@inmuno.org, ezuniga@inmuno.org, luzangelmo@hotmail.com, marevalo@inmuno.org, and sherrera@inmuno.org. Leonardo Mariño-Ramírez, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Computational Biology Branch, Building 38A, Bethesda, MD, E-mail: marino@ncbi.nlm.nih.gov. Ananías A. Escalante, School of Life Sciences, Arizona State University, Tempe, AZ, E-mail: Ananias.Escalante@asu.edu.
Reprint requests: Sócrates Herrera, Malaria Vaccine and Drug Development Center, Carrera 37 - 2Bis No. 5E - 08, Cali, Colombia, E-mail: sherrera@inmuno.org.