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Protective efficacy of mycobacterial 71-kDa cell wall associated protein using poly (DL-lactide-co-glycolide)
1Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Abstract:
Microparticles composed of poly (DL-lactide-co-glycolide) (DL-PLG) were used as delivery vehicles for evaluating the immunoreactive and immunoprotective properties of 71-kDa cell wall associated protein of Mycobacterium tuberculosis H37Ra. Mice immunized with 71-kDa microparticles entrapped in DL-PLG (PLG-MPs) exhibited significantly higher T-cell stimulation and cytokine release in comparison to 71-kDa emulsified in Freund's incomplete adjuvant (FIA) as well as a BCG vaccinated group throughout the post-immunization (p.im.) period. Further, the protective efficacy of 71-kDa was evaluated on the basis of survival rates and viable bacilli load in different organs at 30 days post challenge (p.c.), with the median lethal dose (LD50) of M. tuberculosis H37Rv at weeks 8 and 16 p.im. Both 71-kDa-PLG and 71-kDa-FIA immunized groups exhibited a comparable protection (90%) which was significantly higher (P < 0.5) than in the BCG group (70%) at week 8 p.im. and it was consistent with the decreased bacterial load in the target organs. However, on increasing the interval of challenge to 16 weeks p.im., the protective efficacy of 71-kDa-PLG was sustained (85%) while that of 71-kDa-FIA began to wane (70%). Further. the 71-kDa-PLG immunized group exhibited a significantly higher (P < 0.001) clearance of bacterial load from the lungs and livers in comparison to the 71-kDa-FIA immunized group. The results suggest the long-term protective potential of a PLG-microparticle based antigen delivery system for tuberculosis.
Insights
Poly (DL-lactide-co-glycolide) microparticles enhanced immune responses against tuberculosis. This antigen delivery system showed sustained protection and reduced bacterial load compared to traditional methods.
Area of Science:
- Immunology
- Biotechnology
- Infectious Diseases
Background:
- Tuberculosis (TB) remains a global health challenge, necessitating novel vaccine strategies.
- Developing effective antigen delivery systems is crucial for enhancing vaccine efficacy.
- Mycobacterium tuberculosis cell wall proteins are potential vaccine candidates.
Purpose of the Study:
- To evaluate the immunoreactive and immunoprotective properties of a 71-kDa M. tuberculosis protein delivered via poly (DL-lactide-co-glycolide) microparticles (PLG-MPs).
- To compare the efficacy of PLG-MP delivered antigen with traditional Freund's incomplete adjuvant (FIA) and BCG vaccination.
Main Methods:
- Mice were immunized with 71-kDa protein encapsulated in PLG-MPs or emulsified in FIA.
- Immunological responses were assessed by measuring T-cell stimulation and cytokine release.
- Protective efficacy was evaluated by survival rates and bacterial load in organs post-challenge with M. tuberculosis H37Rv.
Main Results:
- PLG-MP immunization induced significantly higher T-cell stimulation and cytokine release compared to FIA and BCG.
- Both 71-kDa-PLG and 71-kDa-FIA groups showed higher protection (90%) than BCG (70%) at 8 weeks post-immunization.
- PLG-MP delivery sustained protective efficacy (85%) at 16 weeks, while FIA efficacy waned (70%), with superior bacterial clearance in PLG-MP group.
Conclusions:
- Poly (DL-lactide-co-glycolide) microparticles serve as an effective delivery system for M. tuberculosis antigens.
- PLG-MP based delivery enhances both immune response and long-term protection against tuberculosis.
- This approach holds promise for developing advanced tuberculosis vaccines.