eSymposia | Tuberculosis: Science Aimed at Ending the Epidemic

Dec 2, 2020 ‐ Dec 4, 2020



Sessions

Population structure and transmission dynamics of multidrug resistant Mycobacterium tuberculosis strains in Sierra Leone

Dec 2, 2020 12:00am ‐ Dec 2, 2020 12:00am

Population structure and transmission dynamics of multidrug resistant Mycobacterium tuberculosis strains in Sierra Leone Harriet NA Blankson1, 2, Christian Utpatel1, Rashidatu Kamara3, Ivan Barilar1, Sönke Andres4, Tobias Dallenga5, Katharina Kranzer6, Florian Maurer4, Lynda Foray3, Stefan Niemann1, 2 1Molecular and Experimental Mycobacteriology, Research Center Borstel Leibniz Lung Center, Borstel, Germany 2German Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Reims, Borstel, Germany 3National Leprosy and Tuberculosis Control Programme Sierra Leone, Freetown, Sierra Leone 4National Reference Center for Tuberculosis, Research Center Borstel Leibniz Lung Center, Borstel, Germany 5Cellular Microbiology, Research Center Borstel Leibniz Lung Center, Borstel, Germany 6Clinical Research Department, London School of Hygiene and Tropical Medicine, London, United Kingdom Introduction: Drug resistant Mycobacterium tuberculosis complex (Mtbc) strains represent an increasing problem for global tuberculosis control. Particular important are rifampicin/multidrug resistant (RR/MDR) strains, that represent approx. 2.5% of new TB cases in Sierra Leone. As treatment of MDR TB cases is less effective, much longer and more expensive compared to susceptible TB cases, the control of the MDR TB epidemic is of outmost importance. Therefore, it is vital to understand the determinants of the MDR TB epidemic on a regional level to develop effective control measures. Here, we performed whole genome sequencing (WGS) to determine the population structure, resistance levels and transmission patterns of MDR Mtbc strains from Sierra Leone. Methods: A total of 326 culture positive samples from 2003 to 2004 (85 samples, retreatment cases) and from 2016 to 2020 (241samples) were subjected to WGS. RR/MDR strains were selected based on the genotypic drug susceptibility test (gDST). WGS RR/MDR strains were then used for phylogenetic strain classification, and a cluster analysis based on a maximum of ≤12 single nucleotide polymorphisms (SNPs) distances between two strains. Results: There were 247 RR/MDR strains and they were classified into seven major lineages. Most prevalent were lineage 4 strains 61% (151), followed by lineage 6 strains 21% (51) and lineage 2 strains 10% (25). Overall, 19% (47) of the strains were RR, 81% (199) were MDR, and 0.004% (1) was preXDR. 78% (118) and 86% (44) of the lineage 4 and 6 strains were MDR, while 100% (n=10 & 25) of the Lineage 1and 2 strains were MDR. The most prevalent resistance conferring mutations were rpoB S450L and katG S315T for rifampicin and isoniazid respectively. The overall clustering rate was 30%, a total of 106 strains were grouped in 32 clusters, ranging in size from 2 to 16 strains. The largest cluster among MDR strains was formed by 2.2.1 Beijing Ancestral 3 strains, and the second largest cluster by strains of the 4.8 mainly T sublineage. Conclusions: MDR was mostly found in strains of endemic lineages while larger transmission was found in the Beijing ancestral 3 strains. Although MDR tuberculosis is developed, resistance to second line injectables and fluoroquinolone was scarce, an indication that most of the MDR cases in the country could be treated based on the WHO treatment guidelines.

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Monocyte fatty acid transcriptional programs and AMPK polymorphisms associate with resistance to TST/IGRA conversion

Dec 2, 2020 12:00am ‐ Dec 2, 2020 12:00am

Monocyte fatty acid transcriptional programs and AMPK polymorphisms associate with resistance to TST/IGRA conversion J.D. Simmons1*, P.T. Van2, C.M. Stein3,4, V. Chihota5,6, T. Ntshiqa6, P. Maenetje6, G.J. Peterson1, P. Benchek3, K. Velen6, K.L. Fielding5.7, A.D. Grant5,7,8, A.D. Graustein1, F.K. Nguyen1, C. Seshadri1, R. Gottardo2, H. Mayanja-Kizza9, R.S. Wallis6, G. Churchyard6, W.H. Boom4 and T.R. Hawn1 1) TB Research & Training Center, Department o­­­­­f Medicine, University of Washington, Seattle, WA, USA. 2) Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 3) Department of Population & Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA. 4) Department of Medicine, Case Western Reserve University, Cleveland, OH, USA. 5) School of Public Health, University of Witwatersrand, Johannesburg, South Africa. 6) The Aurum Institute, Parktown, South Africa. 7) TB Centre, London School of Hygiene & Tropical Medicine, London, United Kingdom. 8) Africa Health Research Institute, School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa 9) Department of Medicine, School of Medicine, Makerere University, Kampala, Uganda. After extensive exposure to Mycobacterium tuberculosis (Mtb), most individuals acquire latent Mtb infection (LTBI) defined by a positive tuberculin skin test (TST) or interferon-g release assay (IGRA). To identify mechanisms of resistance to Mtb infection, we compared transcriptional profiles of monocytes isolated from highly exposed contacts who resist TST/IGRA conversion (resisters, RSTRs) and controls with LTBI using RNAseq. Gene sets related to central carbon metabolism and the macrophage transcriptional response to free fatty acids (FFAs) strongly enriched across two independent RSTR cohorts suggesting that RSTR and LTBI monocytes have distinct metabolic or activation states. To explore whether FFAs modulate intracellular Mtb replication, we treated healthy donor monocyte-derived macrophages (MDMs) with FFA following Mtb infection and found that palmitic acid (PA) enhanced intracellular growth whereas oleic acid (OA) had no effect. Secretion of TNFa, IL6 and IL1b in Mtb-infected MDMs was inhibited by PA and not OA, which suggests that PA inhibits host-protective pro-inflammatory responses. By limiting the activation of adenosine monophosphate-activated protein kinase (AMPK), PA was previously shown to inhibit autophagy and modulate the pro-inflammatory response. We found that Mtb growth restriction in PA-treated macrophages was restored by co-treatment with an AMPK activator. As a central regulator of carbon metabolism, we explored whether polymorphisms in AMPK associate with RSTR (n=74) or LTBI (n=189) phenotypes. Seven SNPs in the AMPK subunit gene PRKAG2 associated with RSTR status (OR 2.3 – 3.2, p

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TOLLIP resolves lipid-induced EIF2 signaling in alveolar macrophages for durable Mycobacterium tuberculosis protection.

Dec 2, 2020 12:00am ‐ Dec 2, 2020 12:00am

TOLLIP resolves lipid-induced EIF2 signaling in alveolar macrophages for durable Mycobacterium tuberculosis protection. Authors: Sambasivan Venkatasubramanian1, Courtney Plumlee2, Kim Dill-McFarland1, Gemma L. Pearson3, Sara B. Cohen2, Anne Lietzke3, Amanda Pacheco3, Sarah Hinderstein1, Scott A. Soleimanpour3,4, Matthew Altman1, Kevin B. Urdahl2,5, Javeed A. Shah1,7*. Affiliations: 1 Department of Medicine, University of Washington, Seattle, WA. 2 Seattle Children’s Research Institute, Seattle, WA. 3 Department of Internal Medicine, University of Michigan, Ann Arbor, MI. 4 VA Ann Arbor Healthcare System, Ann Arbor, MI. 5 Departments of Pediatrics and Immunology, University of Washington, Seattle, WA. 6 VA Puget Sound Healthcare System, Seattle, WA. Relative deficiency of TOLLIP expression in monocytes is associated with increased tuberculosis (TB) susceptibility in genetic studies, despite antagonizing host innate immune pathways that control Mycobacterium tuberculosis (Mtb) infection in vitro. In this study, we investigated the mechanisms by which TOLLIP influences Mtb immunity. Tollip-/- mice developed worsened disease, consistent with prior genetic observations, and developed large numbers of foam cells. Selective TOLLIP deletion in alveolar macrophages (AM) was sufficient to induce lipid accumulation and increased Mtb persistence 28 days after infection, despite increased antimicrobial responses. We developed a system to analyze sorted, Mtb-infected Tollip-/- AM from mixed bone marrow chimeric mice to measure global gene expression 28 days post-infection. This experiment revealed transcriptional profiles consistent with increased EIF2 signaling. Selective lipid administration to Tollip-/- macrophages induced lipid accumulation, and Mtb infection of lipid laden, Tollip-/- macrophages induced increased cellular stress pathways after Mtb infection, and impaired Mtb control. EIF2 overactivation induced increased Mtb replication within macrophages, irrespective of TOLLIP expression. In humans, TOLLIP and EIF2 signaling complex genes were enriched in human caseous granulomas, compared with healthy lung tissue. Our findings define a critical role for TOLLIP to prevent lipid-induced EIF2 activation that impairs Mtb-infected macrophage activity, and provide targets to improve Mtb clearance during chronic infection.

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MODELLING THE USE OF GENEXPERT AND SMEAR MICROSCOPY ON TIME TO DIAGNOSIS, TREATMENT INITIATION AND TREATMENT OUTCOMES AMONG TB PATIENTS AT UNIVERSITY TEACHING HOSPITALS-ADULT HOSPITAL, CHEST CLINIC, LUSAKA ZAMBIA

Dec 2, 2020 12:00am ‐ Dec 2, 2020 12:00am

MODELLING THE USE OF GENEXPERT AND SMEAR MICROSCOPY ON TIME TO DIAGNOSIS, TREATMENT INITIATION AND TREATMENT OUTCOMES AMONG TB PATIENTS AT UNIVERSITY TEACHING HOSPITALS-ADULT HOSPITAL, CHEST CLINIC, LUSAKA ZAMBIA Title: MODELLING THE USE OF GENEXPERT AND SMEAR MICROSCOPY ON TIME TO DIAGNOSIS, TREATMENT INITIATION AND TREATMENT OUTCOMES AMONG TB PATIENTS AT UNIVERSITY TEACHING HOSPITALS-ADULT HOSPITAL, CHEST CLINIC, LUSAKA ZAMBIA John Mathias Zulu, MSc1; Sheila Masaku, MSc.1; Moses Mukosha, MSc.1 Chipo Nkwemu, MSc.1 Dr. Gershom Chongwe PhD1,2 Dr. Patrick Kaonga, PhD1; Prof. Patrick Musonda PhD1 1University of Zambia-School of Public Health, 2Tropical Diseases Research Centre Abstract Background: Timely diagnosis and treatment initiation are important determinants of TB prevention and treatment outcomes. The study explored the diagnostic performance of the GeneXpert and Smear Microscopy on time to diagnosis, treatment initiation, and improvement of treatment outcomes. Methods: A retrospective cohort study which followed up TB patients who used the GeneXpert and smear microscopy at UTH-chest clinic from 2015 january-2019 December. Median time was analyzed at two levels, time to diagnosis and time to treatment initiation. Multivariable Cox proportion models were used to analyze predictors of treatment initiation. While lognormal regression model was used to determine predictors of unfavorable outcomes. A p-value of 0.05 was deemed statistically significant. Results: A total of 417 TB patients were enrolled in the study, 243 (58.3%) used GeneXpert, and 174(42.7%) used the smear microscopy. Of the total patients, 299(70.5%) were diagnosed in 5 days. Of the total participants, 229(54.0%) were treated in 14days. Further, 156(45.0%) had successful and 191(55.0%) unsuccessful outcomes. Compared to smear, in Xpert arm median days of diagnosis were 1 day [IQR] 1–41) versus 4 days [IQR] 1–15), p

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Changes in the blood transcriptome following prophylactic treatment reflect latent tuberculosis heterogeneity

Dec 2, 2020 12:00am ‐ Dec 2, 2020 12:00am

Changes in the blood transcriptome following prophylactic treatment reflect latent tuberculosis heterogeneity Julie G Burel1, Akul Singhania1, Paige Dubelko1, Julius Muller2, Rachel Tanner2, Eneida Parizotto2, Martin Dedicoat3, Thomas E. Fletcher4,5, James Dunbar6, Adam F. Cunningham7, Cecilia S. Lindestam Arlehamn1, Donald G Catanzaro8, Antonino Catanzaro9, Timothy C Rodwell9, Helen McShane2, Matthew K. O’Shea3,4,7 and Bjoern Peters1,9 1 Vaccine Discovery Division, La Jolla Institute for Immunology, La Jolla, CA, USA; 2 The Jenner Institute, University of Oxford, Oxford, UK; 3 University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; 4 Royal Centre for Defence Medicine, Joint Medical Command, Birmingham, UK; 5 Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK 6 Department of Infectious Diseases, The Friarage Hospital, Northallerton, UK; 7 Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK; 8 Department of Biological Sciences, University of Arkansas, Fayetteville, AR, USA 9 Department of Medicine, University of California San Diego, CA, USA Abstract: About 2 billion people are infected with Mycobacterium tuberculosis (Mtb) worldwide, representing a considerable potential transmission reservoir which hampers eradication efforts. Prioritizing latent tuberculosis (LTBI) patients who would benefit most from chemoprophylaxis treatment would improve TB control strategies. We hypothesized that LTBI individuals at risk of developing active TB (ATB) display immunological profiles more similar to those with ATB than the LTBI cohort at large, and thus will exhibit a similar signature in response to treatment. We studied changes in the blood transcriptome in a cohort of 42 LTBI patients who received anti-TB therapy. Before starting treatment, the LTBI cohort was divided into high, intermediate and low risk of progression to active disease based on the expression of previously published gene signatures of ‘risk of progression to active TB’ (Riskhigh, Riskint and Risklow groups, respectively). We found that LTBI Riskhigh and LTBI Risklow groups were associated with two distinct transcriptomic signatures after treatment, with LTBI Riskhigh resembling ATB and associating with IFNg signaling and activated T cells. Importantly, some of the treatment signatures genes were already differentially expressed between LTBI Riskhigh and LTBI Risklow groups prior to treatment, suggesting the transcriptomic reprogramming following treatment in LTBI can be predicted. We conclude that pre-treatment blood RNA signatures in individuals with LTBI can be used to predict immune profiles following therapy, which represents a promising approach to identify individuals who would most likely benefit from therapeutic intervention.

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Risk Factors for Incurable Drug-Resistant Tuberculosis: A Systematic Review

Dec 2, 2020 12:00am ‐ Dec 2, 2020 12:00am

Risk Factors for Incurable Drug-Resistant Tuberculosis: A Systematic Review Authors and Affiliations: Karan Varshney, MPH, Beverly Anaele, MPH, Rosemary Frasso, PhD, MSc, MSc, CPH Abstract: Tuberculosis (TB) caused more deaths worldwide in 2018 than any other single infectious disease. In recent years, there has been an upsurge in cases of drug-resistant TB, and strains of TB resistant to all forms of treatment have begun to emerge. There is an urgent need to prevent TB that is completely resistant to treatment, and knowing the risk factors can inform prevention efforts. For the purpose of this systematic review, we identified and analyzed 25 articles, published since 2010, that examined relevant risk factors. We found that the most commonly reported risk for patients developing drug-resistant TB was having a history of TB. Other important risk factors were human immunodeficiency virus (HIV), a history of incarceration, low body mass, being a smoker, alcohol use, unemployment, being male, and being middle-aged. The findings show that adherence to treatment is crucial amongst TB patients, and that more efforts are needed to increase adherence rates in the population. HIV programs need to be scaled up in areas where both diseases are endemic. Efforts are also needed to raise awareness that smoking is a risk factor. More studies on risk factors for patients need to be conducted in India and Russia, where drug-resistant TB rates are highest. To our knowledge, this is the first systematic review to examine the risk factors for incurable drug-resistant TB. Keywords: drug-resistant, tuberculosis, risk factors, compliance, adherence, XDR-TB,

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Sirtuin 3 downregulation links metabolic reprogramming, mitochondrial oxidative stress and cell death in macrophages infected with Mycobacterium tuberculosis

Dec 2, 2020 12:00am ‐ Dec 2, 2020 12:00am

Sirtuin 3 downregulation links metabolic reprogramming, mitochondrial oxidative stress and cell death in macrophages infected with Mycobacterium tuberculosis Smulan L1, Martinez N1, Kiristy MC1, Kativhu C1, Cavallo K1, Sassetti CM1, Singhal A2, Remold HG3, Kornfeld H1 1University of Massachusetts Medical School, MA; 2Agency for Science, Technology and Research (A*STAR), Singapore; 3Brigham and Women’s Hospital, Harvard Medical School, MA Mycobacterium tuberculosis (M. tuberculosis) rewires macrophage metabolism whereby glucose metabolism is shifted from oxidative phosphorylation (OXPHOS) towards glycolysis, possibly as a means to fuel a rapid inflammatory response. Although metabolic reprogramming, initiated by the bacillus, has been identified in human and mouse macrophages and in murine lungs, the mechanisms driving M. tuberculosis-mediated metabolic reprogramming remain unknown. Sirtuin (SIRT) 3, an NAD+-dependent protein deacetylase, is an important regulator of mitochondrial metabolism and cellular redox homeostasis. We hypothesized that modulation of SIRT3 in macrophages contributes to M. tuberculosis-mediated mitochondrial metabolic rewiring and stress. Here, we investigate the effect of M. tuberculosis infection on SIRT3 and downstream targets in murine macrophages. Following infection of macrophages, we found reduced SIRT3 mRNA and protein levels which was mediated through TLR signaling. This downregulation was associated with reduced expression of the SIRT3 target, isocitrate dehydrogenase 2 (IDH2), a key enzyme in the tricarboxylic acid (TCA) cycle. The IDH2 substrate, isocitrate, was also found to be increased indicating a block within the TCA cycle following infection. Expression of electron transport chain complex I subunits were also downregulated, resulting in reduced complex I activity. Coinciding with decreased OXPHOS, infected macrophages had decreased glutathione levels, and accumulation of mitochondrial reactive oxygen species (mtROS) leading to macrophage death. We found these alterations to be SIRT3-dependent as Sirt3-/- macrophages showed decreased expression of IDH2 and complex I subunits, along with decreased glutathione and increased mtROS compared to wild type macrophages. Lungs of M. tuberculosis-infected Sirt3-/- mice had greater bacterial burden and immune pathology compared to wild type mice showing relevance to tuberculosis (TB) disease in vivo. All together, our findings suggest that M. tuberculosis downregulates SIRT3 through TLR signaling resulting in an altered mitochondrial metabolic state and oxidative stress which ultimately impacts TB pathogenesis. This work was supported by NIH grants HL081149 and HL127384.

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HostSim: a virtual host framework to analyze the immune response to vaccination and Mycobacterium tuberculosis infection

Dec 2, 2020 12:00am ‐ Dec 2, 2020 12:00am

HostSim: a virtual host framework to analyze the immune response to vaccination and Mycobacterium tuberculosis infection Louis R. Joslyn1, Jennifer J. Linderman2, Denise E. Kirschner3 1Department of Computational Medicine & Bioinformatics, University of Michigan Medical School, 100 Washtenaw Avenue, Ann Arbor, MI. 2Department of Chemical Engineering, University of Michigan, 2800 Plymouth Rd, NCRC B28, Ann Arbor, MI, 48109-2800; 3Department of Microbiology and Immunology, University of Michigan Medical School, 1150 W Medical Center Drive, 5641 Medical Science II, Ann Arbor, MI 48109-5620; To address outstanding questions related to M. tuberculosis (Mtb) infection, reinfection and vaccination, we developed a new computational tool, HostSim, that follows the immune response and infection at the host level. HostSim captures cells, cytokines, and bacterial dynamics tracking formation, dissemination and function of multiple granulomas, the hallmark of Mtb infection, across an entire virtual lung. HostSim also tracks immune cells within lung draining lymph nodes and blood to predict how T-cell priming, proliferation, and differentiation in response to Mtb antigens impacts whole-host outcomes, such as sterilization. HostSim is calibrated to experimental datasets across the cellular, granuloma, whole-lung, and whole-host scales of non-human primates. Altogether, this multi-scale and multi-compartment computational model allows us to represent a whole-body response to vaccination and infection. Through a series of parallel in silico experiments, we predict mechanisms that underlie protection, and why some individuals might exhibit greater protection than others. These results have implications for vaccination strategies against tuberculosis. Importantly, we use this new virtual host framework to develop a protocol for virtual pre-clinical trials. We predict dynamics and effects of vaccine-derived T cells throughout the course of Mtb infection. This study highlights the power of a systems biology approach to narrow and focus vaccine studies prior to experiments.

Speaker(s):

Immune variations throughout the course of tuberculosis treatment and its relationship with adrenal hormone changes in HIV-1 patients co-infected with Mycobacterium tuberculosis

Dec 2, 2020 12:00am ‐ Dec 2, 2020 12:00am

Immune variations throughout the course of tuberculosis treatment and its relationship with adrenal hormone changes in HIV-1 patients co-infected with Mycobacterium tuberculosis Maria Belen Vecchione 1, Denise Anabella Giannone 1, Matías Tomás Angerami 1, Natalia Laufer 1;2, Omar Sued 3 and Maria Florencia Quiroga 1. 1 Universidad de Buenos Aires. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS). Facultad de Medicina. Buenos Aires, Argentina. 2 Hospital Juan A. Fernández. Buenos Aires, Argentina. 3 Área de Investigaciones Médicas. Fundación Huésped. Buenos Aires, Argentina. Purpose: Risk of developing active TB among HIV-coinfected (HIV-TB) patients is 19 times higher than in HIV-negative individuals. Host's immune response determines resolution or dissemination of TB infection. We aimed to identify immuno-endocrine responses over a six-month follow-up of anti-tuberculous (anti-TB) treatment in HIV+ individuals that were associated with control of TB. Methods: Plasma levels of cortisol, DHEA and DHEA-S (DHEA sulfate), percentages of CD4+ regulatory T cell subsets and number of IFN-γ-secreting cells were determined. Several cytokines, chemokines and C-reactive protein (CRP) levels were measured. Results were analyzed, correlated with clinical data and compared to similar data from HIV-1-monoinfected individuals, HIV infected individuals with latent TB infection and healthy donors. Results: Throughout the course of anti-TB/HIV treatment, reduction of viral load (p

Speaker(s):
  • Maria B. Vecchione, PhD, Instituto de Investigaciones Biomedicas en Retrovirus y SIDA (U.B.A.-CONICET)

A novel therapeutic vaccine against multi-drug resistant tuberculosis by T cell mediated immunity in phase 1 clinical trial.

Dec 2, 2020 12:00am ‐ Dec 2, 2020 12:00am

A novel therapeutic vaccine against multi-drug resistant tuberculosis by T cell mediated immunity in phase 1 clinical trial. Masaji Okada1, Kazunori Tomono2, Kazunari Tsuyuguchi1, Takefumi Saito3, Yoshikazu  Inoue1, Akira Yamane4 ,Soichiro Watanabe5 1National Hospital Organization Kinki-chuo Chest Medical Center, 2Osaka University; 3NHO Ibaraki-higashi Hospital, 4NHO Tokyo Hospital, 5Muroran-city General Hospital Multi-drug resistant (MDR), especially extremely drug resistant (XDR), Mycobacterium tuberculosis (M. TB) is a serious problem in the world. We have developed novel TB therapeutic vaccine (HVJ-E/HSP65 DNA +IL-12 DNA vaccine) to eliminate MDR-TB by T cells. DNA vaccine expressing M.TB heat shock protein 65 and IL-12 was delivered by the hemagglutinating virus of Japan (HVJ)-envelope. Results: This vaccine provided remarkable therapeutic efficacy against MDR-TB and XDR-TB in murine models (decrease in the number of MDR-TB). Furthermore, this vaccine provided therapeutic efficacy of prolongation of survival time (100% survival) of TB infected monkeys and augmented the T cell immune responses. Preclinical study by using monkeys in GLP level, safety of the vaccine was shown. 【Phase1 Investigator-initiated clinical trial】 Therefore, phase 1 clinical trial has been already started. Targets are human patients with MDR-TB. Primary evaluation is safety and tolerability. Secondary evaluation is anti-TB efficacy (sputum-culture conversion). A patient of First Patient In showed safety and tolerability of this therapeutic vaccine by pDNA concentration in the blood. Furthermore, anti-TB efficacy (MDR-TB negative conversion) was demonstrated by the Gaffky study and colony count of TB in the sputum. Anti-TB immunity (IFN-γ and IL-2 production) was augmented in the patient with this vaccination from 14~126 day. Conclusion: These data indicate that HSP65 DNA+IL-12DNA vaccine is useful against XDR-TB and MDR-TB through T cells for human therapeutic clinical applications. (This research was supported by AMED,Japan.)

Speaker(s):
  • Masaji Okada, MD, PhD, National Hospital Organization Kinki-chuo Chest Medical Center
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