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Johannes Nemeth @johannesnemeth.bsky.social · 10d

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

Johannes Nemeth @johannesnemeth.bsky.social · 10d

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.

Johannes Nemeth @johannesnemeth.bsky.social · 10d

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.

Johannes Nemeth @johannesnemeth.bsky.social · 10d

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.

Johannes Nemeth @johannesnemeth.bsky.social · 10d

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.

Safety of Bacillus Calmette-Guérin vaccination and impact on HIV-1 latent reservoir size in people with treated HIV-1 Infection

Johannes Nemeth @johannesnemeth.bsky.social · 10d

We just published results from the BELIEVE trial—a small, investigator-initiated study testing BCG vaccination in people with treated HIV. academic.oup.com/ofid/advance...

AbstractBackground. Bacillus Calmette-Guérin (BCG) vaccination, used against tuberculosis, is recognized for its immunomodulatory properties, a phenomenon

A deadly equation: The global toll of US TB funding cuts

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Reposted by Johannes Nemeth

Karen Attiah @karenattiah.bsky.social · 22d

I gave my heart and soul to that place. Built entire sections for journalists pushed out of their home countries.

When the writer I hired, Jamal Khashoggi was murdered by Saudi Arabia, they paraded me around as a symbol for press freedom.

I put MY LIFE on the line to defend journalism and WaPo.

bmazing.bsky.social @bmazing.bsky.social · 23d

weird that neither of these articles two main stories decrying censorship mention WaPo's firing of @karenattiah.bsky.social I guess democracy really does die in darkness

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Johannes Nemeth @johannesnemeth.bsky.social · 28d

A new modeling study highlights the stakes of recent U.S. funding cuts for TB programs. Without rapid recovery, 26 high-burden countries could see up to 10.7M excess TB cases and 2.2M more deaths by 2030. An urgent call for global reinvestment in TB control.
dx.plos.org/10.1371/jour...

The recent withdrawal of U.S. financial support threatens essential TB service delivery, including diagnostics, treatment, TB-HIV co-infection interventions and research initiatives critical to eradic...

dx.plos.org

Johannes Nemeth @johannesnemeth.bsky.social · 29d

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

Johannes Nemeth @johannesnemeth.bsky.social · 29d

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.

Johannes Nemeth @johannesnemeth.bsky.social · 29d

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.

Johannes Nemeth @johannesnemeth.bsky.social · 29d

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.

Johannes Nemeth @johannesnemeth.bsky.social · 29d

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.

c-Myc Inhibits Macrophage Antimycobacterial Response in Mycobacterium tuberculosis Infection

Johannes Nemeth @johannesnemeth.bsky.social · 29d

What do cancer and tuberculosis have in common?
A shared reliance on c-Myc to suppress immune defenses.
In our latest study, we uncover how Mycobacterium tuberculosis exploits this pathway to persist inside macrophages—even in the presence of IFN-γ. academic.oup.com/jid/advance-...

c-Myc is an important regulator of macrophage function during Mycobacterium tuberculosis infection. Its inhibition enhances bacterial control, whereas its

Machine Learning-based Prediction of Active Tuberculosis in People With Human Immunodeficiency Virus Using Clinical Data

Johannes Nemeth @johannesnemeth.bsky.social · Sep 9

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-...

Machine learning models can predict incident active tuberculosis in people with HIV (PWH) using routine medical data, outperforming current tests. This may

Johannes Nemeth @johannesnemeth.bsky.social · Sep 7

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).

Infection with Mycobacterium tuberculosis alters the antibody response to HIV-1

Reposted by Johannes Nemeth

Madhu Pai, MD, PhD @madhupai.bsky.social · Aug 30

We simply cannot allow this to happen

Children deserve better

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Johannes Nemeth @johannesnemeth.bsky.social · Aug 30

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.

Author summary Active Mycobacterium tuberculosis (MTB) infection remains a leading cause of death among people with HIV-1 (PWH). However, the majority of PWH infected with MTB do not progress to activ...

journals.plos.org

Johannes Nemeth @johannesnemeth.bsky.social · Aug 28

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

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

Inflammation and B cell activation define a plasma proteome signature predicting tuberculosis in people with HIV | mBio

We still lack reliable tools to predict who will develop tuberculosis (TB) among people with HIV. Moreover, the underlying biological events driving progression remain poorly understood. Our study reveals early immune changes that include unexpected ...

journals.asm.org

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Johannes Nemeth @johannesnemeth.bsky.social · Aug 28

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.

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Johannes Nemeth @johannesnemeth.bsky.social · Aug 28

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.

Johannes Nemeth @johannesnemeth.bsky.social · Aug 28

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.