Adjunctive immunotherapy with α-crystallin based DNA vaccination reduces Tuberculosis chemotherapy period in chronically infected mice

Chauhan, Priyanka; Jain, Ruchi; Dey, Bappaditya; Tyagi, Anil K.

doi:10.1038/srep01821

Cited by 16 publications

(14 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The emergence of drug-resistant TB strains makes global TB control a real challenge. Immunotherapy is regarded as a potential approach to eliminate MTB [22,23]. The vehicles used to deliver specific antigens are very important in immunotherapy [24,25].…”

Section: Discussionmentioning

confidence: 99%

A lentiviral vector-based therapeutic vaccine encoding Ag85B-Rv3425 potently increases resistance to acute tuberculosis infection in mice

Yang¹,

Wang²,

Xu³

et al. 2015

ABBS

View full text Add to dashboard Cite

Few treatment options for multidrug-resistant tuberculosis (TB) and extensively drug-resistant TB call attention to the development of novel therapeutic approaches for TB. Therapeutic vaccines are promising candidates because they can induce antigen-specific cellular immune responses, which play an important role in the elimination of Mycobacterium tuberculosis (MTB). In this study, a novel lentiviral vector therapeutic vaccine for delivering MTB-specific fusion protein Ag85B-Rv3425 was constructed. Results showed that one single-injection of this recombinant lentivirus vaccine could trigger antigen-specific Th1-type immune responses in mice. More importantly, mice with acute infection benefited a lot from a single-dose administration of this vaccine by markedly reduced MTB burdens in lungs and spleens as well as attenuated lesions in lungs compared with untreated mice. These results displayed good prospects of this novel vaccine for the immunotherapy of TB.

show abstract

Section: Discussionmentioning

confidence: 99%

A lentiviral vector-based therapeutic vaccine encoding Ag85B-Rv3425 potently increases resistance to acute tuberculosis infection in mice

Yang¹,

Wang²,

Xu³

et al. 2015

ABBS

View full text Add to dashboard Cite

show abstract

“…DNA vaccines have shown promise in their ability to enhance the activity of antibiotic treatment and reduce reactivation of LTBI and transmission (323)(324)(325). Adjunctive immunotherapy with a DNA vaccine containing the LTBI marker ␣-crystallin (233,(328)(329)(330) reduces the duration of antibiotic treatment in chronically infected mice (331). Similarly, RUTI, a therapeutic vaccine comprising detoxified, fragmented M. tuberculosis cells delivered in liposomes, also has been shown to enhance the effect of short-course chemotherapy in animal models (326) and is currently being evaluated in clinical trials (327).…”

Section: Reactivation Of Ltbimentioning

confidence: 99%

Latent Tuberculosis Infection: Myths, Models, and Molecular Mechanisms

Dutta

Karakousis

2014

Microbiol Mol Biol Rev

195

174

View full text Add to dashboard Cite

SUMMARY The aim of this review is to present the current state of knowledge on human latent tuberculosis infection (LTBI) based on clinical studies and observations, as well as experimental in vitro and animal models. Several key terms are defined, including “latency,” “persistence,” “dormancy,” and “antibiotic tolerance.” Dogmas prevalent in the field are critically examined based on available clinical and experimental data, including the long-held beliefs that infection is either latent or active, that LTBI represents a small population of nonreplicating, “dormant” bacilli, and that caseous granulomas are the haven for LTBI. The role of host factors, such as CD4 + and CD8 + T cells, T regulatory cells, tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ), in controlling TB infection is discussed. We also highlight microbial regulatory and metabolic pathways implicated in bacillary growth restriction and antibiotic tolerance under various physiologically relevant conditions. Finally, we pose several clinically important questions, which remain unanswered and will serve to stimulate future research on LTBI.

show abstract

“…The potential of this protein as a vaccine candidate has been investigated in several animal models [ 7 – 11 ] and encouraging results were reported. For example, adjunctive immunotherapy of mice with a DNA vaccine expressing Rv2031 was shown to significantly reduce bacillary load, shorten treatment duration, result in complete restoration of lung architecture and prevent reactivation [ 10 ]. Similarly, in guinea pigs, Rv2031-based vaccination was shown to impart protection against TB through enhanced production of IL-12, IL-10 and TGF-β [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Pro- and Anti-Inflammatory Cytokines against Rv2031 Are Elevated during Latent Tuberculosis: A Study in Cohorts of Tuberculosis Patients, Household Contacts and Community Controls in an Endemic Setting

et al. 2015

View full text Add to dashboard Cite

Tuberculosis (TB) is among the leading causes of morbidity and mortality. The causative agent, Mycobacterium tuberculosis (Mtb), has evolved virulent factors for entry, survival, multiplication and immune evasion. Rv2031 (also called alpha crystallin, hspX, 16-kDa antigen), one of the most immunogenic latency antigens, is believed to play a key role in long-term viability of Mtb. Here, we report the dynamics of pro-inflammatory (IFN-γ, TNF-α) and anti-inflammatory (IL-10) cytokines against Rv2031 using whole blood assay in human cohorts in a TB endemic setting. Cytokine responses to ESAT-6-CFP-10 were also measured for comparison. Blood samples were collected from smear positive pulmonary TB patients and their contacts at baseline, 6 and 12 months, and from community controls at entry. At baseline, 54.4% of controls and 73.2% of contacts were QFT-GIT test positive. Baseline IFN-γ, TNF-α and IL-10 responses to Rv2031 were significantly higher in controls compared to contacts and untreated patients (p<0.001). Furthermore, untreated patients had significantly higher TNF-α and IL-10 responses to Rv2031 compared to contacts (p<0.001). In contacts and treated patients, IFN-γ, TNF-α and IL-10 responses to Rv2031 significantly increased over 12 months (p<0.0001) and became comparable with the corresponding levels in controls. There was a positive and significant correlation between Rv2031 and ESAT-6-CFP-10 specific cytokine responses in each study group. The fact that the levels of IFN-γ, TNF-α and IL-10 against Rv2031 were highest during latent TB infection may indicate their potential as markers of protection against TB. Taken together, the findings of this study suggest the potential of IFN-γ, TNF-α and IL-10 against Rv2031 as biomarkers of the host response to Mtb during convalescence from, and the absence of, active tuberculosis.

show abstract

Adjunctive immunotherapy with α-crystallin based DNA vaccination reduces Tuberculosis chemotherapy period in chronically infected mice

Cited by 16 publications

References 46 publications

A lentiviral vector-based therapeutic vaccine encoding Ag85B-Rv3425 potently increases resistance to acute tuberculosis infection in mice

A lentiviral vector-based therapeutic vaccine encoding Ag85B-Rv3425 potently increases resistance to acute tuberculosis infection in mice

Latent Tuberculosis Infection: Myths, Models, and Molecular Mechanisms

Pro- and Anti-Inflammatory Cytokines against Rv2031 Are Elevated during Latent Tuberculosis: A Study in Cohorts of Tuberculosis Patients, Household Contacts and Community Controls in an Endemic Setting

Contact Info

Product

Resources

About