IOSR Journal of Biotechnology and Biochemistry (IOSR-JBB) ISSN: 2455-264X, Volume 3, Issue 4 (Jul. – Aug. 2017), PP 12-18 www.iosrjournals.org DOI: 10.9790/264X-03041218 www.iosrjournals.org 12 | Page Lait Nocard to rBCG - Over 100 Years of Experience with BCG Vaccine * Mathan Periasamy, Manjula Datta, M. Kannapiran Department of Biotechnology, Sree Sastha Institute of Engineering and Technology, Chennai-123, India Department of Epidemiology (Rtd), the Tamilnadu Dr. M.G.R. Medical University, Chennai-32, India Department of Biochemistry (Rtd), National Institute for Research in Tuberculosis, ICMR, Chennai-31, India. Corresponding Author: Mathan Periasamy --------------------------------------------------------------------------------------------------------------------------------------- Date of Submission: 04-07-2017 Date of acceptance: 15-07-2017 --------------------------------------------------------------------------------------------------------------------------------------- I. Introduction Tuberculosis (TB) continues to be a major worldwide health problem and is the leading killer of youth and adults in developing countries, being responsible for more deaths than any other single infectious organism [1]. 5–15% of the people infected with M. tuberculosis (estimated 2–3 billion) will develop TB disease during their lifetime [1]. Bacillus Calmette–Guerin (BCG), an attenuated strain of Mycobacterium bovis is the only vaccine currently available against TB. This is the world‟s most widely used vaccine and being directed against the world‟s leading cause of infectious disease mortality, BCG is the most controversial vaccine in cur rent use [2]. The efficacy of BCG vaccine in the prevention of tuberculosis has shown considerable variation in different populations and trials [3]. Results from those trials showed 0-80% of protection and particularly those from South India have shown no protection. The on-going research on new TB vaccines may take several years as it involves earlier safety testing and efficacy field trials. This review article discusses about the earlier historical attempts to the recent advancements in TB vaccines with special reference to modern recombinant vaccines. II. Earlier History behind BCG In 1896, Leon Charles Albert Calmette (1863 – 1933), a French physician was appointed as the director of the Pasteur Institute of Lille, France, and the main public problem which he had to contend with was tuberculosis. Meantime, Jean Marie Camille Guerin (1872 – 1961), a French veterinary surgeon was appointed to assist Calmette in 1897 and both have decided to proceed with research on tuberculosis vaccine [4]. In 1902, Edmond Nocard (1850 – 1903), a French veterinarian and microbiologist isolated a virulent M. bovis strain from a cow with tuberculous mastitis. This bovine strain, “Lait Nocard,” was sent to Pasteur Institute, Lille for further investigations by Calmette and Guerin. Laboratory Standardization has showed that it has Less virulence in human beings but Capable to induce the immune system. Later, Calmette and Guerin finalised to design a live vaccine from this „Lait nocard‟. They observed that addition of ox bile to the medium leads to th e lowering of the virulence of the organism and this observation led them to take their long-term attempt to prepare a vaccine from live attenuated bacilli. They started their subculture work with a virulent bovine strain of tubercle bacillus in 1908. They cultured the bacilli on bile, glycerin and potato medium and then preceded to subculture at three weeks intervals. By 1919 after about 230 subcultures carried out for 11 years they succeeded to get attenuated live bacillus (later referred as BCG) which failed to produce progressive disease in animals [4]. The first human administration of BCG was carried-out on 18th July 1921 by Benjamin Weill Halle (1875-1958), through oral route. By 1924, they administrated oral BCG to 664 infants. After these reports of successful BCG vaccination, cultures of BCG were delivered for propagation in laboratories all over the world. The original M. bovis BCG vaccine strain was developed into several different sub strains which have been used for production of BCG vaccine. Between 1924 and 1926, 34 countries received BCG cultures from Pasteur institute (TABLE – 1) and later, many other countries were also reported to have received BCG cultures from Paris [5]. TABLE – 1: List of Countries to which BCG cultures were distributed from Pasteur Institute between 1924 and 1926 [5] Names of Countries Algeria Canada Italy Peru Switzerland Argentina Columbia Japan Poland Syria Austria Czechoslovakia Lithuania Romania Uruguay Belgium Germany Mauritius Russia USA Bolivia Greece Mexico Scotland Venezuela Brazil Holland Norway Spain Yugoslavia Bulgaria Hungary Palestine Sweden