China
Africa
Explore chapters and articles related to this topic
BCG and Other Vaccines
Published in Lloyd N. Friedman, Martin Dedicoat, Peter D. O. Davies, Clinical Tuberculosis, 2020
AERAS-422 was designed to combine the two strategies, over-expressing Ag85A, Ag85B, and Rv3407, while also expressing perfringolysin (with the same aim as listeriolysin in VPM1002). Further development of this vaccine was terminated due to the reactivation of latent Varicella zoster infection in two subjects during phase I clinical trials.143 Of the three rBCG vaccines that have entered phase I trials (rBCG30, AERAS-422, and VPM1002), only VPM1002 remains in active development.
Bacille Calmette–Guerin and Prospects for New Vaccines against Tuberculosis
Published in Peter D O Davies, Stephen B Gordon, Geraint Davies, Clinical Tuberculosis, 2014
There are two approaches to generating a genetically improved BCG. The first is simply to add in antigens that BCG currently expresses at a low level (e.g. Antigen 85B in rBCG30) or to add in antigens from M. tuberculosis that BCG does not currently express (e.g. ESAT6) [60,61]. One example of this approach, rBCG30, is a recombinant strain of Tice BCG that over-expresses Antigen 85B [60]. This vaccine was found to be superior to wild-type Tice BCG against M. tuberculosis challenge in guinea pigs and has been evaluated in a clinical trial in the United States [62]. Although this construct is now not in active clinical development, there are similar newer generation vaccines being developed.
Drug targets in dormant Mycobacterium tuberculosis: can the conquest against tuberculosis become a reality?
Published in Infectious Diseases, 2018
Vivek Kumar Gupta, M. Madhan Kumar, Dharmendra Singh, Deepa Bisht, Shweta Sharma
Anti-TB drugs which are in the pipeline may also be promising in the treatment options for LTBI. In this context, five new chemical entities (bedaquiline [13], (delamanid (OPC-67683) [14], pretomanid (PA-824) [15], sutezolid (PNU-100480) [16], Q203 [17]) for treating TB are being evaluated in clinical trials (Table 1). Bedaquiline, a new antibiotic which was introduced after a long time for treating MDR TB in adults also represents a hope for LTBI because it inhibits ATP synthesis which is a common target present in both dormant as well as replicating bacilli [13]. The study by Lanoix et al. has assessed the potency of three new drugs (viz. bedaquiline, pretomanid, sutezolid and/or one or two fluoroquinolones) for treating LTBI in mice [16]. These drugs were tested alone and also in combination employing experimental paucibacillary chemotherapy model for LTBI. The study used BALB/c and C3HeB/FeJ strains (model in which necrotizing granulomas are produced like humans with LTBI) of mice which were vaccinated with a recombinant Mycobacterium bovis bacillus Calmette-Guérin strain (rBCG30) and the mice were then infected by giving a low-dose aerosol of Mtb H37Rv. The control mice were administered RIF or INH (standard anti TB drugs). In both the strains, regimens which contained bedaquiline and the combination of pretomanid and sutezolid were the most active test regimens and their efficacy was comparable to rifampin. On the other hand, as individual drugs, pretomanid, sutezolid and levofloxacin manifested activity similar to isoniazid. The authors suggest that certain drugs alone or in combinations (bedaquiline alone, pretomanid alone or in combination with sutezolid or a fluoroquinolone) can be effective in treating latently infected individuals associated with multi drug resistant TB (MDR TB) after testing these regimens in clinical trials.