Development of recombinant Mycobacterium smegmatis (MS) expressing B- and T-cell epitopes of latency associated antigens of Mycobacterium tuberculosis (MTB) as a TB vaccine candidate

Tuberculosis (TB) remains a major public health problem worldwide. Nearly one-third of the world population is latently infected with Mycobacterium tuberculosis (MTB) and 5 - 10 % of infected individuals will develop active disease during their life time. Bacille Calmette–Guérin (BCG) efficiently pr...

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Bibliographic Details
Main Author: Ismail, Mohd Zakuan
Format: Thesis
Language:English
Published: 2017
Subjects:
Online Access:http://eprints.usm.my/43103/1/Dr._Mohd_Zakuan_Ismail-24_pages.pdf
Description
Summary:Tuberculosis (TB) remains a major public health problem worldwide. Nearly one-third of the world population is latently infected with Mycobacterium tuberculosis (MTB) and 5 - 10 % of infected individuals will develop active disease during their life time. Bacille Calmette–Guérin (BCG) efficiently protects against severe disease manifestations in children, but does not prevent the establishment of latent TB or reactivation of TB pulmonary disease in adult life. Therefore, in order to control this scourge from exacerbating, the development of an effective TB vaccine is an urgent priority. The expression of MTB antigens in Mycobacterium smegmatis (MS) is one of the potential strategies for the development of new generation vaccines against TB. This study focused on the construction and evaluation of immunogenicity in Balb/C mice of a recombinant MS (rMS) expressing B- and T-cell epitopes of Latency-Associated Antigens (LAA) (Rv2005c, Rv2031c, Rv3130c, Rv3127) of MTB (rMS081). The capacity of rMS081 to induce specific humoral and cellular immune responses against expressed B- and T-cell epitopes was evaluated. Total specific Immunoglobulin G (IgG) showed a significant increase against all epitopes (Rv2005c, Rv2031c, Rv3130c, Rv3127) in the sera of rMS081-immunized mice compared with the control group. In the experimental conditions evaluated, there were no significant increase in the cytokines, Interferon-gamma (IFN-), Interleukin (IL)-2 and IL-4 against the LAA epitopes in the rMS081-immunized mice compared with the control group. The results obtained support the future evaluation of rMS081 as a vaccine candidate against TB in challenge studies.