We’re now building on this with new studies, diving deeper into how mycobacterial signals might modulate immune persistence in HIV.

#HIV #ClinicalTrials #BCG #Immunology #HIVCure #TeamScience

We didn’t see a significant change in the HIV-1 reservoir. But the study lays important groundwork for future research on host-pathogen interactions in HIV—and validates our department’s capacity for running IITs.

The results? BCG was safe overall—but local reactions (often leading to scarring) were common. No systemic complications occurred. This is reassuring in a population historically excluded from live vaccines.

With strong support from the Von Tobel Stiftung, we launched BELIEVE: a randomized, placebo-controlled trial in people with long-term viral suppression and good immune recovery.

Each participant received BCG or placebo, with careful monitoring and reservoir quantification.

The idea might sound unusual: a TB vaccine in people with HIV? But there’s a long-standing hypothesis behind it.

We’ve been exploring how self-limiting mycobacterial exposures might shape the human immune system—including its interaction with the HIV reservoir.

This work was a major collaborative effort across Zurich 🇨🇭 and Seattle 🇺🇸.
We’re excited about what it means for the future of TB immunotherapy—and for understanding immune evasion across diseases. #TB #cMyc #Macrophages #HostDirectedTherapy

We also saw elevated c-Myc expression in:

- mouse lung lesions

- granulomas in human TB patients

- immune cells in persistent infection zones
c-Myc isn't just a passenger—it’s a gatekeeper of immune suppression.

Why does this matter?
Because even in active TB—where IFN-γ is abundant—immune control often fails. Our findings suggest that high c-Myc expression creates an immune-privileged niche, similar to cancer.
Targeting this axis could unlock host-directed therapies in TB and beyond.

And here’s the biotech twist:
We used an inducible lentiviral system to selectively block c-Myc in mature macrophages—without affecting cell viability or baseline function.
That’s not just cool science—it’s a biotechnological feat in immune cell engineering.

Co–first authors Edoardo Sarti and Cédric Dollé showed that inhibiting c-Myc in fully differentiated macrophages reprograms them into a more powerful, antimicrobial state.
This reprogramming boosts key effectors like iNOS and TNF-α and reshapes macrophage metabolism via mTORC1.

Really interesting! We also found BMI is a strong predictor of TB in PWH — lipids/cholesterol too — suggesting classic overweight markers may be inversely associated with TB risk. Raises lots of questions regarding nutrition, infection risk an ID. Thx for sharing! academic.oup.com/cid/advance-...

Thank you for your interest. Yes, I think so. We applied for funding to investigate this in other contexts (Tx patients), hoping to find a correlate of „immune tension“ (lacking better names for it).

Yes, totally agree. Didn‘t expect that. Also, TB affects HIV antibody response -> See this: journals.plos.org/plospathogen... I am not sure how all of this fits together but for me TB ≠ TB/HIV, quite confident about that.

The full open-access paper is now out in mBio:
journals.asm.org/doi/10.1128/...

#USZ #HIV #Tuberculosis #Proteomics #MachineLearning #SwissHIVCohort #Biomarkers #Immunology

Our findings highlight the potential of integrating proteomic and clinical data to improve TB prediction in people with HIV—an area where current diagnostic tools fall short.

They also suggest an underappreciated role of humoral immunity in TB pathogenesis.

We identified a distinct proteomic signature linked to TB progression, defined by systemic inflammation, B cell activation, and changes in immunoglobulin levels.

The classifier achieved 0.77 AUC and revealed immune shifts far before clinical onset.

Led by Katharina Kusejko and Mohammad Arefian, with Ben Collins and colleagues, we analyzed 583 plasma samples from the Swiss HIV Cohort Study.

These included individuals who developed TB up to 4 years later—and matched controls who did not.