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Host-directed immunotherapy of viral and bacterial infections: past, present and future

Nature Reviews Immunology volume 23, pages 121–133 (2023)Cite this article

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Abstract

The advent of COVID-19 and the persistent threat of infectious diseases such as tuberculosis, malaria, influenza and HIV/AIDS remind us of the marked impact that infections continue to have on public health. Some of the most effective protective measures are vaccines but these have been difficult to develop for some of these infectious diseases even after decades of research. The development of drugs and immunotherapies acting directly against the pathogen can be equally challenging, and such pathogen-directed therapeutics have the potential disadvantage of selecting for resistance. An alternative approach is provided by host-directed therapies, which interfere with host cellular processes required for pathogen survival or replication, or target the host immune response to infection (immunotherapies) to either augment immunity or ameliorate immunopathology. Here, we provide a historical perspective of host-directed immunotherapeutic interventions for viral and bacterial infections and then focus on SARS-CoV-2 and Mycobacterium tuberculosis, two major human pathogens of the current era, to indicate the key lessons learned and discuss candidate immunotherapeutic approaches, with a focus on drugs currently in clinical trials.

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Fig. 1: Timeline of key developments in host-directed immunotherapeutic interventions for infectious disease.
Fig. 2: Host-directed immunotherapeutic intervention points for severe COVID-19.
Fig. 3: Interferons and immunotherapeutic intervention: COVID-19 and tuberculosis.
Fig. 4: Major candidates for host-directed immunotherapies and their targets in tuberculosis.

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Acknowledgements

The authors thank E. Wall and W. Blanchett for helpful suggestions on the manuscript. The contribution of R.S.W. was partially supported by Horizon 2020 grant 847465 for Research and Innovation (DRTB-HDT) and project RIA2019AMR-2647 (panTB-HM) of the EDCTP2 programme of the European Union. The contribution of A.W. was funded by The Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001206), the UK Medical Research Council (FC001206) and the Wellcome Trust (FC001206). A.O’G. is funded by The Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001126), the UK Medical Research Council (FC001126) and the Wellcome Trust (FC001126). A.S. is supported by the intramural research program of the National Institute of Allergy and Infectious Diseases, US National Institutes of Health.

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Authors and Affiliations

  1. The Aurum Institute, Johannesburg, South Africa

    Robert S. Wallis

  2. Vanderbilt University, Nashville, TN, USA

    Robert S. Wallis

  3. Rutgers University, Newark, NJ, USA

    Robert S. Wallis

  4. Case Western Reserve University, Cleveland, OH, USA

    Robert S. Wallis

  5. Immunoregulation and Infection Laboratory, The Francis Crick Institute, London, UK

    Anne O’Garra

  6. National Heart and Lung Institute, Imperial College London, London, UK

    Anne O’Garra

  7. Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    Alan Sher

  8. Immunoregulation Laboratory, The Francis Crick Institute, London, UK

    Andreas Wack

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  4. Andreas Wack
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The authors contributed equally to all aspects of the article.

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Wallis, R.S., O’Garra, A., Sher, A. et al. Host-directed immunotherapy of viral and bacterial infections: past, present and future. Nat Rev Immunol 23, 121–133 (2023). https://doi.org/10.1038/s41577-022-00734-z

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