Evolution ofM. bovisBCG Vaccine: Is Niacin Production Still a Valid Biomarker?

Abstract

BCG vaccine is usually considered to be safe though rarely serious complications have also been reported, often incriminating contamination of the seed strain with pathogenic Mycobacterium tuberculosis. In such circumstances, it becomes prudent to rule out the contamination of the vaccine seed. M. bovis BCG can be confirmed by the absence of nitrate reductase, negative niacin test, and resistance to pyrazinamide and cycloserine. Recently in India, some stocks were found to be niacin positive which led to a national controversy and closer of a vaccine production plant. This prompted us to write this review and the comparative biochemical and genotypic studies were carried out on the these contentious vaccine stocks at the Indian vaccine plant and other seeds and it was found that some BCG vaccine strains and even some strains of M. bovis with eugenic-growth characteristics mainly old laboratory strains may give a positive niacin reaction. Most probably, the repeated subcultures lead to undefined changes at the genetic level in these seed strains. These changing biological characteristics envisage reevaluation of biochemical characters of existing BCG vaccine seeds and framing of newer guidelines for manufacturing, production, safety, and effectiveness of BCG vaccine.

Immunological Characterization of Proteins Expressed by Genes Located in Mycobacterium tuberculosis-Specific Genomic Regions Encoding the ESAT6-like Proteins

“…The proteins encoded by RD1 are considered more promising in vaccine applications because this region is present in all clinical M. tuberculosis isolates [ 89 , 90 , 91 , 92 ]. Furthermore, RD1 is absent in all sub-strains of BCG [ 93 , 94 , 95 , 96 ] because of its deletion during the attenuation of the parent BCG strain obtained by prolonged sub-culturing of pathogenic M. bovis in an artificial medium [ 97 ], and hence the application of RD1-encoded immunodominant antigens in the diagnosis of TB is not expected to have any effect due to BCG vaccination [ 98 , 99 , 100 , 101 ]. Interestingly, the ESAT6 gene is located in RD1, and the gene for another low molecular weight and immunodominant protein, known as the 10 kDa culture filtrate protein (CFP10), is also present in the RD1 region [ 102 ].…”

Defensins: The Case for Their Use against Mycobacterial Infections

“…In 2013, an estimated 9.0 million people developed tuberculosis, and 1.5 million died from the disease [ 1 ]. Almost all cases of tuberculosis are caused by M. tuberculosis , with M. bovis contributing less than 1.4% of all pulmonary cases outside of Africa and ~2.8% of cases in Africa with a crude incidence of 7 cases per 100,000 population [ 2 ]. The incidence of disease in some countries is also exacerbated by HIV infections [ 1 ].…”