Protective efficacy of mycobacterial 71-kDa cell wall associated protein using poly (dl-lactide-co-glycolide) microparticles as carrier vehicles

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.

Single-injection vaccines: Progress, challenges, and opportunities

“…Controlled release devices have been used to encapsulate a large number of antigens against diseases as diverse as the plague [88,89], bacterial pneumonia [90], meningitis [91], tuberculosis [92], brucellosis [93], and anthrax [70]. On the whole, these studies demonstrate a similar adjuvant effect of controlled release devices that results in a stronger immune response, but with additional stability issues.…”

Next generation vaccines: single-dose encapsulated vaccines for improved global immunisation coverage and efficacy

“…Another attempt at stabilising and protecting the Ag from damage during particle synthesis, by entrapping it in an oil‐based core of PLGA microparticles, resulted in a discrete in vitro release pattern with bursts after 3 or 7 weeks, depending on the L : G ratio in the PLGA particle composition [84]. A rare study investigating the protective efficacy of PLGA‐encapsulated mycobacterial protein (PLGA‐MP) against tuberculosis challenge in mice found significantly superior and longer lasting protection by PLGA‐MP when compared with the BCG vaccine and a small improvement over MP adjuvanted with incomplete Freund's adjuvant [85]…”

“…[84] A rare study investigating the protective efficacy of PLGA-encapsulated mycobacterial protein (PLGA-MP) against tuberculosis challenge in mice found significantly superior and longer lasting protection by PLGA-MP when compared with the BCG vaccine and a small improvement over MP adjuvanted with incomplete Freund's adjuvant. [85] Addition of adjuvants is another aspect of formulating encapsulated vaccines for delayed release and improving their immunogenicity. Using HBsAg as model antigen in mice, Singh et al demonstrated that encapsulated HBsAg results in immune responses comparable to three individual injections of HBsAg adsorbed to aluminium (Al)-based adjuvant, and these responses were maintained for over a year.…”

Poly(lactic acid‐glycolic acid) nanoparticles markedly improve immunological protection provided by peptide P10 against murine paracoccidioidomycosis

“…Antigens encapsulated within polymers can be released for a prolonged period at a controlled rate of polymer degradation (Vicent and Duncan, 2006). Polymers have been shown to be effective adjuvants for various antigenic proteins, including ovalbumin, cholera and tetanus toxoid, and malarial and pneumotrophic bacterial antigens (Dhiman and Khuller, 1998;Jaganathan et al, 2005). Poly(lactic acid-glycolic acid) (PLGA) is a polymer whose degradation rate and antigen release can be predicted (Jiang et al, 2005).…”