Norhanani, Mohd Redzwan
(2008)
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.
Masters thesis, Universiti Sains Malaysia.
Abstract
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.
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