title: Immunogenic potential of latency associated antigens against Mycobacterium tuberculosis.
abstract: Tuberculosis remains a great health threat to the world among infectious diseases particularly with the advent of human immunodeficiency virus and emergence of drug resistant strains. In the light of the inconsistent efficacy imparted by the only currently available pre-exposure vaccine bacillus Calmette-Guerin BCG, the development of an improved TB vaccine is a very high international research priority. Vaccine candidates currently in clinical trials are also pre-exposure vaccines that aim to prevent active tuberculosis during an individual's lifetime. According to World Health Organization approximately a third of the world's population is latently infected with Mycobacterium tuberculosis. Dormancy or latency of Mycobacteria is associated with the formation of granuloma with poorly perfused interior leading to expression of genes which help them survive in this hostile environment. A group of about 50 genes belonging to the DosR regulon also known as latency antigens are expressed by Mycobacteria when they are persisting in the immuno-competent host. An understanding of the immunological effects produced by products of these latency induced genes may help in making a more potent vaccine. Incorporation of latency antigens into improved (live or subunit) vaccines may enhance the impact of these vaccines in which BCG priming can be followed by multisubunit protein boosting. These vaccines could act as post exposure vaccines for containment and prevention of latent TB activation. This heterologous boosting of BCG-primed immunity will be able to stimulate the known immune correlates of protective immunity against M. tuberculosis i.e. TH1 cells (CD4(+) and CD8(+) T cells) mediated immune responses with cytokines such as IFN-γ and TNF-α⋅ In our review we have analysed and compared the immunogenic potential of various latency-associated antigens of the DosR regulon in line with the current strategy of developing a recombinant post exposure booster vaccine.
authors.affiliation: DS Kothari Centre for Research and Innovation in Science Education, Miranda House, University of Delhi, Delhi 110007, India. Electronic address: singhswati.mh@gmail.com.
authors.forename: Swati
authors.initials: S
authors.lastname: Singh
authors.affiliation: DS Kothari Centre for Research and Innovation in Science Education, Miranda House, University of Delhi, Delhi 110007, India. Electronic address: etisaraav@gmail.com.
authors.forename: Iti
authors.initials: I
authors.lastname: Saraav
authors.affiliation: DS Kothari Centre for Research and Innovation in Science Education, Miranda House, University of Delhi, Delhi 110007, India. Electronic address: sadhnas@rediffmail.com.
authors.forename: Sadhna
authors.initials: S
authors.lastname: Sharma
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins; D006801:Humans; D055985:Latent Tuberculosis / Q000276:immunology*; D009169:Mycobacterium tuberculosis; D011494:Protein Kinases / Q000235:genetics / Q000276:immunology; D018085:Regulon; D014376:Tuberculosis / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C542863:DosR protein, Mycobacterium tuberculosis; D032581:Tuberculosis Vaccines; D014614:Vaccines, Synthetic; D011494:Protein Kinases; C542862:DosT protein, Mycobacterium tuberculosis
keywords: BCG; CFP10; CO; DNA; DOTS; DosR; DosR regulon; ESAT-6; GLA-SE; H1; HIV; HLA; HspX; IFN-γ; Latency antigens; Latent tuberculosis; MTB; MVA.85A; Mycobacterium tuberculosis; NO; PBMC; TB; TNF-α; Vaccine candidates; bacillus Calmette–Guerin; carbon monoxide; culture filtrate protein-10; deoxyribonucleic acid; directly observed treatment, short course; dormancy survival regulon; early secretory antigenic target; glucopyranosyl lipid adjuvant-stable emulsion; heat shock protein X; human immunodeficiency virus; human leucocyte antigen; hybrid1; interferon gamma; modified vaccinia virus Ankara expressing mycobacterial antigen 85A; nitric oxide; peripheral blood mononuclear cell; rBCG; recombinant BCG; tuberculosis; tumor necrosis factor alpha