Evaluation of the potential of Mycobacterium smegmatis as vaccine Candidate against tuberculosis by in silico and in vivo studies

  • Thi Thuy Le-Nguyen Biotechnology Centre of Ho Chi Minh City
  • Reinier Borrero-Maura Instituto Finlay
  • Sonsire Férnandez Instituto Finlay
  • Giselle Reyes Instituto Finlay
  • José Luis Perez Instituto Finlay
  • Fátima Reyes Instituto Finlay
  • María de los Angeles García Instituto Finlay
  • Midrey Fariñas Instituto Finlay
  • Juan Francisco Infante Instituto Finlay
  • Yanely Tirado Instituto Finlay
  • Alina Puig Instituto Finlay
  • Gustavo Sierra Instituto Finlay
  • Nadine Álvarez Instituto Finlay
  • Juan Carlos Ramírez Instituto Finlay
  • María Elena Sarmiento Instituto Finlay
  • Mohd Nor Norazmi School of Health Sciences, Universiti Sains Malaysia
  • Armando Acosta Instituto Finlay

Resumen

In this study, we scanned multiple published databases of gene expression in vivo of M. tuberculosis at different phases of infection in animals and humans, to select 38 proteins that are highly expressed in the active, latent and reactivation phases. The selected proteins were predicted for T and B epitopes. For each proteins, the regions containing T and B epitopes were selected at the same time to look for identical epitopes on M. smegmatis based on sequence alignments. Preliminary studies of humoral immunogenicity and cross-reactivity with M. tuberculosis in mice using two M. smegmatis-derived experimental vaccines were carried out, demonstrating the immunogenicity of M. smegmatis proteoliposomes and the recognition of M. tuberculosis proteins by the sera of animals immunized with this vaccine candidate. The conjunction of in silico and in vivo studies suggested the potential for future evaluation of M. smegmatis as vaccine candidate against tuberculosis using different strategies.

Citas

World Health Organization. Global tuberculosis control: surveillance, planning, financing: WHO report 2008. WHO Library Cataloguing-in-Publication Data:1-37.

Dietrich J, Lundberg CV, Andersen P. TB vaccine strategies - What in needed to solve a complex problem? Tuberculosis 2006;86:163-8.

Davies MN, Flower DR. Harnessing bioinformatics to discover new vaccines. Drug Discovery Today 2007; 12:389-96.

Cayabyab MJ, Hovav AH, Hsu T, Krivulka GR, Lifton MA, Gorgone DA, et al. Generation of CD8+ T-Cell responses by a recombinant nonpathogenic Mycobacterium smegmatis vaccine vector expressing human immunodeficiency virus type 1 Env. J Virology 2006; 56:1645-52.

Mawuenyega KG, Forst CV, Dobos KM, Belisle JT, Chen J, Bradbury EM, et al. Mycobacterium tuberculosis functional network analysis by global subcellular protein profiling. Molecular Biology of the Cell 2004; 16:396-404.

Wallis RS, Perkins M, Phillips M. Induction of the antigen 85 complex of Mycobacterium tuberculosis in sputum: A determinant of outcome in pulmonary tuberculosis treatment. J Infectious Diseases 1998;178:1115-21.

Fenhall G, Stevens L, Moses L, Bezuidenhout J, Betts JC. In Situ detection of Mycobacterium tuberculosis transcripts in human lung granulomas reveals differential gene expression necrotic lesions. IAI 2002; 70:6330-8.

Timm J, Post FA, Gail L. Differential expression of iron-, carbon, and oxygenresponsive mycobacterial genes in the lungs of chronically infected mice and tuberculosis patients. PNAS 2003; 100:14321-6.

Shi L, Jung YJ, Tyagi S. Expression of Th1-mediated immunity in mouse lungs induces a Mycobacterium tuberculosis transcription pattern characteristic of nonreplicating persistence. PNAS 2003; 100:241-6.

Shi L, North R, Gennaro ML. Effect of growth state on transcription levels of genes encoding major secreted antigens of Mycobacterium tuberculosis in the mouse lung. IAI 2004; 72:2420-4.

Talaat AM, Lyons R, Howard ST, Johnston SA. The temporal expression profile of Mycobacterium tuberculosis infection in mice. PNAS 2004; 101:4602-7.

Karakousis PC, Yoshimatsu T, Lamichhane G, Woolwine SC, Nuermbeger EL. Dormancy phenotype displayed by extracellular Mycobacterium tuberculosis within artifical granulomas in mice. J Exp Med 2004; 200: 647-57.

Tufariello JM, Jacobs WR, Chan J. Individual Mycobacterium tuberculosis resuscitation-promoting factor homologues are dispensable for growth in-vitro and in-vivo. Infect Immun 2004; 72:515-26.

Dubnau E, Chan J, Mohan VP, Smith I. Responses of Mycobacterium tuberculosis to growth in the mouse lung. IAI 2005; 73:3754-7.

Delogu G, Sanguinetti M, Posteraro B. The hbhA gene of Mycobacterium tuberculosis is specifically upregulated in the lungs but not in the spleens of aerogenically infected mice. IAI 2006; 74:3006-11.

Rachman H, Strong M, Ulrichs T, Grode L, Schuchhardt J. Unique transcriptome signature of Mycobacterium tuberculosis in pulmonary tuberculosis. IAI 2006;74:1233-42.

Talaat AM, Ward SK, Wu CW, Rondon E. Mycobacterial bacilli are metabolically active during chronic tuberculosis in murine lungs: Insights from genome-wide transcriptional profiling. J Bacteriology 2007; 189:4265-74.

Garton NJ, Waddell SJ, Sherratt AL, Lee SM, Smith RJ. Cytological and transcript analyses reveal fat and lazy persisterlike bacilli in tuberculous sputum. PLoS Med 2008; 5:1371-82.

Rustad TR, Harrell MI, Liao R, Sherman DR. The enduring hypoxic response of Mycobacterium tuberculosis. PloS ONE 2008;7:1502-9.

Srivastava V, Jain A, Srivastava BS. Selection of genes of Mycobacterium tuberculosis upregulated during residence in lungs of infected mice. Tuberculosis 2008; 88:171-7.

Kesavan AK, Brooks M, Tufariello JA, Chan J, Manabe YC. Tuberculosis genes expressed during persistence and reactivation in the resistant rabbit model. Tuberculosis 2009; 89:17-21.

Davies AP, Dhillon AP, Young M. Resuscitation-promoting factors are expressed in Mycobacterium tuberculosis-infected human tissue. Tuberculosis 2008;88:462-8.

Ãlvarez N, Borrero R, García MA, Martínez I, Acosta M, Padrón MA, et al. Obtención y caracterización parcial de un extracto lipídico de la membrana externa de Mycobacterium smegmatis. VacciMonitor 2009;18:15-9.

Zhang M, Kim KJ, Iyer D, Lin YG, Belisle J, McEnery K, et al. Effects of Mycobacterium tuberculosis on the bioelectric properties of the alveolar epithelium. Infect Immun 2007; 65:692-8.

Olivares N, León A, López Y, Puig A, Cádiz A, Falero G, et al. The effect of the administration of human gamma globulins in a model of BCG infection in mice. Tuberculosis 2006; 86:268-72.

Kuehnel MP, Goethe R, Habermann A, Mueller E, Rodeh M, Grifiths S, Valentin-Weigand M. Characterization of the intracellular survival of Mycobacterium avium ssp. paratuberculosis: phagosomal pH and fusogenicity in J774 macrophages compared with other mycobacteria. Cell Microbiol 2001; 3:551-66.

Publicado
2016-03-15
Cómo citar
Le-Nguyen, T., Borrero-Maura, R., Férnandez, S., Reyes, G., Perez, J., Reyes, F., García, M., Fariñas, M., Infante, J., Tirado, Y., Puig, A., Sierra, G., ÁlvarezN., Ramírez, J., Sarmiento, M., Norazmi, M., & Acosta, A. (2016). Evaluation of the potential of Mycobacterium smegmatis as vaccine Candidate against tuberculosis by in silico and in vivo studies. VacciMonitor, 19(1), 20-26. Recuperado a partir de https://vaccimonitor.finlay.edu.cu/index.php/vaccimonitor/article/view/100
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Artículos Originales