Immunological studies of dna (pjwvacll) and surface display (r-stvacll) vaccine candidates expressing a synthetic mul tiepitope gene of mycobacterium tuberculosis in a prime boost strategy using a mouse model

• Main Author: Norhanani, Mohd Redzwan
• Format: Thesis
• Language: English
• Published: 2008
• Subjects: R Medicine (General)
• Online Access: http://eprints.usm.my/52092/1/NORHANANI%20BINTI%20MOHD%20REDZWAN%20-%2024%20pages.pdf; http://eprints.usm.my/52092/
• Institution: Universiti Sains Malaysia

Tuberculosis (TB) in humans is caused by the bacterial pathogen Mycobacterium tuberculosis and is still a major health problem worldwide. The only TB vaccine currently available is an attenuated strain of M. bovis; Bacille Calmette Guerin (BCG). BCG demonstrated variable protective efficacies ranging from 0 to 80% in different field trials. BCG is effective at preventing childhood manifestation of TB but it does not prevent the most prevalent disease which is pulmonary TB in adults. DNA vaccination is an important new approach to the control of infectious agents and induces both humoral and cellular immune responses. Two previously constructed vaccine candidates, pJWVacll and r-STVacll were used in this study employing a prime-boost strategy. The naked DNA vaccine, pJWVacll was given intramuscularly to mice whilst the surface display vaccine, r-STVacll was given orally. Splenocytes from the vaccinated mice were tested for various immunological tests. The results showed that splenocytes from immunized mice were found to proliferate more aggressively when stimulated with the antigen (lnak-nVacll). Flow cytometric intracellular cytokine analysis of splenocytes from vaccinated mice also showed that both CD4+ and CD8+ T cells produce IL-2 and IFN-y following stimulation with the antigens. In the prime-boost approach, the study showed that mice primed with the naked DNA vaccine, pJWVacll and boosted with the surface display vaccine, r-STVacll is the best strategy to stimulate immune response in mice. As a conclusion, the data obtained from this study suggest that DNA vaccination in combination with surface display vaccination using prime-boost approach provides a new strategy for developing a candidate vaccine against TB.