Protective capacity of proteoliposomes from Mycobacterium bovis BCG in a mouse model of tuberculosis

Abstract

Tuberculosis (TB) is one of the most important causes of mortality and morbidity due to infectious diseases. BCG, the vaccine in use, is not fully protective against TB. In a previous study, we have shown that proteoliposomes (outer membrane extracts), obtained from BCG (PLBCG) were able to induce humoral immune responses against Mycobacterium tuberculosis (Mtb) antigens. With the objective to evaluate the protective capability of PLBCG alone or as a booster with BCG, a murine model of progressive pulmonary TB was used. Animals immunized with PLBCG adjuvanted with alum (PLBCG-Al) showed similar protection to that conferred by BCG. The group immunized with PLBCG-Al as a booster to BCG gave superior protection than BCG as evidenced by a reduction of bacterial load in lungs 2 months after infection with Mtb. Animals immunized with BCG, PLBCG-Al and this formulation as a booster of BCG, showed a significant decrease of tissue damage (percentage of pneumonic area/lung) compared with non-immunized animals. These results demonstrate that immunization with PLBCG-Al alone or as a booster to BCG induce appropriate protection against challenge with Mtb in mice and support the future evaluation of PLBCG as a promising vaccine candidate against Mtb.

Keywords:

• BCG
• prime-boost
• proteoliposomes
• Tuberculosis
• vaccines

Abbreviations:

• TB, Tuberculosis
• Mtb, Mycobacterium tuberculosis
• PL Proteoliposomes
• BCG, Bacillus Calmette-Guerin
• PBS, Phosphate Buffer Solution
• CFU, Colony Forming Unit
• PLBCG, Proteoliposomes obtained from BCG
• PLBCG-Al, PLBCG adjuvanted with alum
• SD, standard deviation

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

The authors acknowledge Dr. Reynaldo Acevedo for his kind cooperation in this work.

Funding

Funding was provided under the Long-term Research Grant Scheme (203/PSK/6722001), Ministry of Education, Malaysia, the Ministry of Science and Technology, Cuba, and the Institute of Science and Technology of Mexico city (PICSA12-173). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.