a booster vaccine expressing a latency-associated antigen augments bcg induced immunity and confers enhanced protection against tuberculosis助推器增强bcg疫苗表达latency-associated抗原诱导免疫和授予增强预防结核病.pdfVIP

A Booster Vaccine Expressing a Latency-Associated Antigen Augments BCG Induced Immunity and Confers Enhanced Protection against Tuberculosis 1. 1. 2 2 3 1 Bappaditya Dey , Ruchi Jain , Umesh D. Gupta , V. M. Katoch , V. D. Ramanathan , Anil K. Tyagi * 1 Department of Biochemistry, University of Delhi South Campus, New Delhi, India, 2 National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Agra, Uttar Pradesh, India, 3 Department of Clinical Pathology, Tuberculosis Research Center, Chennai, Tamil Nadu, India Abstract Background: In spite of a consistent protection against tuberculosis (TB) in children, Mycobacterium bovis Bacille Calmette- Guerin (BCG) fails to provide adequate protection against the disease in adults as well as against reactivation of latent infections or exogenous reinfections. It has been speculated that failure to generate adequate memory T cell response, elicitation of inadequate immune response against latency-associated antigens and inability to impart long-term immunity against M. tuberculosis infections are some of the key factors responsible for the limited efficiency of BCG in controlling TB. Methods/Principal Findings: In this study, we evaluated the ability of a DNA vaccine expressing a-crystallin- a key latency antigen of M. tuberculosis to boost the BCG induced immunity. ‘BCG prime – DNA boost’ regimen (B/D) confers robust protection in guinea pigs along with a reduced pathology in comparison to BCG vaccination (1.37 log10 and 1.96 log10 fewer bacilli in lungs and spleen, respectively; p ,0.01). In addition, B/D regimen also confers enhanced protection in mice. Further, we show that B/D immunization in mice