Boosting with recombinant MVA expressing M. tuberculosis α-crystallin antigen augments the protection imparted by BCG against tuberculosis in guinea pigs

• Published in: Scientific reports 2017-12, Vol.7 (1), p.17286-14, Article 17286
• Main Authors: Nangpal, Prachi, Bahal, Ritika Kar, Tyagi, Anil K.
• Format: Article
• Language: English
• Subjects: 13/106; 13/109; 38/35; 631/326/421; 631/326/590/1867; alpha-Crystallins - immunology; Animals; Antigens, Bacterial - immunology; Bacilli; Bacillus Calmette-Guerin vaccine; BCG; BCG Vaccine - administration & dosage; BCG Vaccine - immunology; Children; Crystallin; Cytokines - metabolism; Disease Models, Animal; Female; Guinea Pigs; Humanities and Social Sciences; Immunization, Secondary; Lungs; multidisciplinary; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - immunology; Recombinant Proteins - administration & dosage; Recombinant Proteins - immunology; Science; Science (multidisciplinary); Spleen; Tuberculosis; Tuberculosis Vaccines - administration & dosage; Tuberculosis Vaccines - immunology; Tuberculosis, Pulmonary - immunology; Tuberculosis, Pulmonary - microbiology; Tuberculosis, Pulmonary - prevention & control; Vaccination; Vaccines; Viral Vaccines - administration & dosage; Viral Vaccines - immunology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-17587-5

Tuberculosis (TB) is one of the major causes of mortality all over the globe. BCG, the only vaccine available against this disease has been successful in preventing the severe forms of childhood TB. However, the unsatisfactory performance of BCG in controlling the adult pulmonary tuberculosis has made the development of an effective vaccine against M. tuberculosis a prime objective of the TB research. In this study, a genetically stable, marker-free recombinant MVA expressing α-crystallin of M. tuberculosis (rMVA. acr ) was generated which was further evaluated for its ability to impart protection as a booster vaccine against tuberculosis in a heterologous prime boost approach. Our results demonstrated that intradermal delivery of rMVA. acr was able to efficiently boost the BCG induced protection against M. tuberculosis infection in guinea pigs by significantly reducing the pulmonary bacillary load (1.27 log 10 fewer bacilli) in comparison to BCG vaccination alone. In addition, boosting BCG vaccinated animals with intramuscular delivery of rMVA. acr resulted in significantly superior protective efficacy in both lungs and spleen with 0.83 log 10 and 0.74 log 10 CFU fewer bacilli, respectively, when compared to animals vaccinated with BCG only. These findings establish the promise of this prime-boost strategy involving rMVA. acr in enhancing the efficacy of BCG.