This Week in TB R&D – July 20, 2010

19 Jul 2010
by Working Group

Fourth Annual New England TB Symposium

On Friday, July 16th, the fourth annual New England TB Symposium took place at the Broad Institute, in Cambridge, Massachusetts. The symposium was in collaboration with the US-Japan Cooperative Medical Sciences Program: 45th Tuberculosis and Leprosy Research Conference which preceded the symposium at the Broad from July 13-15th.

A brief synopsis of some of the symposium speaker presentations are highlighted below (complete list of speakers are listed on the meeting agenda.) Presentation topics for the TB Symposium were divided into 3 sessions: Molecular and Immunopathogenesis of TB/HIV Infection, Translatable Techniques and Model Systems, and Clinical TB/HIV Infection.

Joel Ernst, New York University, discussed his thoughts on the present knowledge gaps in TB basic biology, how low funding for TB research has created these bottlenecks in TB understanding, and what opportunities exist in understanding human immune responses to HIV/TB co-infection, particularly as it relates to creating better TB vaccines.

Marianne Mureithi, a postdoctoral fellow of K-RiTH, Durban, South Africa and the Ragon Institute, presented research on the impact of HIV-1 infection on the ability of monocytes to respond to M. Tb and M. Tb-encoded Toll-like receptors (TLR) ligands (TLR2, -4, and -8). Results suggest that monocyte response is significantly impaired in the context of HIV infection causing exhaustion of the immune system, increased sickness and active TB in HIV infected individuals. Research involving the vitamin D receptor and the cathelicidin gene were briefly discussed. A manuscript is in press for this work.

John MacMicking, Yale University, suggested that HIV/TB co-infection may create a case of interferon-ɣ (IFN-ɣ) hypomorphism, and implicated p47 GTPases and p65 guanylate-binding proteins in mycobacterial host defense mechanisms.

Paul Clapham, University of Massachusetts, Worcester, shared data on HIV tropism and sensitization to CD4 interactions.

Andy Tager, Harvard Medical School, discussed the generation of humanized BLT mice and how infection of this mouse model with HIV can be used to investigate ‘human’ HIV-specific responses.

Dan Barouch, Harvard Medical School, presented data on the generation of replication-incompetent adenovirus serotype (rAd) 26 and rAd35 vectors and their use to create the next generation HIV-1 vaccine.

Victoria Kasprowicz, Harvard Medical School, shared the need for immunodiagnostics, biomarkers, and the impact of TB on the HIV community. She also emphasized the need for standardizing the collection and storage of patient samples based on experiences with human cohort based studies in Durban, South Africa.

Athe Tsibris, Broad Institute, presented results of the use of deep sequencing of the V3-loop of HIV-1 env, a determinant for HIV infection, and determined: 1) not all sequences obtained are relevant and useful, and 2) there is a lot of genetic diversity in this region (~200-1600 unique sequences were identified) as observed from only 4 patient samples.

Uli von Andrian, Harvard Medical School, showed data of their research using multiphoton intravital microscopy to image immune cell responses in lymph nodes of anesthesized mice injected with virus.

Asha Anandaiah, Kadamba Papavinasasundaram, and Peter Tonge were the three poster abstract winners who gave mini-presentations of their research. The titles of their talks were ‘Vitamin D rescues HIV-infected macrophage host defense responses to Mycobacterium tuberculosis’, ‘A Ser/Thr phosphosignaling system controls cell-wall synthesis in mycobacteria’, and ‘Slow onset inhibitors of mycobacterial fatty acid biosynthesis: residence time, in vivo activity, and in vivo imaging’, respectively.

Carol Mitnik, Harvard Medical School- discussed the current situation facing clinical trials for treatment of multidrug resistant TB, clinical trial capacity, inclusion of women, children, and HIV-coinfected individuals. She also highlighted the global pipeline, research challenges and future opportunities.

Tim Lahey, Dartmouth Medical School, described the Dar Dar trial, a trial to investigate immune protection from HIV-associated TB using heat-inactivated Mycobacterium vaccae (MV) as an investigational vaccine. The need for identifying biomarkers of protection was also discussed and CCL2, -3, and -4, chemotactic receptors were postulated to be more promising biomarkers than IFN–ɣ.

Awewura Kwara, Brown University, showed results that suggested that in Ghanaians, drug-drug interactions between the NNRTIs and rifampin-containing tuberculosis therapy may be caused by induction of CYP2B6. Results observed are similar to a study published in HIV-infected children.

Anne Goldfeld, Harvard School of Public Health, presented results from the CAMELIA (CAMbodian Early (2 weeks) vs. Late (8 weeks) Introduction of Antiretroviral drugs) trial which suggested early introduction of ART decreased mortality. All of the conclusions and data will be shared this week at the International AIDS Conference in Vienna. Details and results from CAPRIT, another trial study, will also be presented at the conference.

KEYNOTE LECTURE – William Bishai, Johns Hopkins Center for Tuberculosis Research, gave a talk entitled ‘Drug-resistant TB: fitness, frailty, and the future.’ He presented a brief timeline of TB history with the identification and treatment of TB, the observance and rise of MDR-TB, particularly in South Africa, and shared research results from his lab on a novel M. tb resistance mechanism to isoniazid mediated by sigma factor 1 mutation. He concluded with asking the audience whether we will squander or capitalize on the tools, technologies, and opportunities that we have as we see to eliminate TB globally.

Overall, the meeting was a good overview of the basic research, clinical advances and challenges facing our understanding of TB and HIV co-morbidity.

Did you attend this meeting? What were your thoughts about the research presented? Please share your thoughts below.

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