Here, I introduce the concept of ‘integrated organ immunity’ to explain how the innate and adaptive immune systems and non-haematopoietic cells can interact in tissues to generate enduring protective immunity against diverse pathogens in an antigen-agnostic manner. Considering immune responses through this framework could enable the design of a new class of vaccines termed ‘universal vaccines’ that are not pathogen specific.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Netea, M. G. et al. Defining trained immunity and its role in health and disease. Nat. Rev. Immunol. 20, 375–388 (2020).
Ziogas, A. et al. Trained immunity: target for prophylaxis and therapy. Cell Host Microbe 31, 1776–1791 (2023).
Aaby, P. et al. Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period? J. Infect. Dis. 204, 245–252 (2011).
Higgins, J. P. et al. Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review. BMJ 355, i5170 (2016).
Arts, R. J. W. et al. BCG vaccination protects against experimental viral infection in humans through the induction of cytokines associated with trained immunity. Cell Host Microbe 23, 89–100 e105 (2018).
Wimmers, F. et al. The single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination. Cell 184, 3915–3935 e3921 (2021).
Lee, A. et al. BCG vaccination stimulates integrated organ immunity by feedback of the adaptive immune response to imprint prolonged innate antiviral resistance. Nat. Immunol. 25, 41–53 (2024).
Kaufmann, E. et al. BCG educates hematopoietic stem cells to generate protective innate immunity against tuberculosis. Cell 172, 176–190 e119 (2018).
Darrah, P. A. et al. Prevention of tuberculosis in macaques after intravenous BCG immunization. Nature 577, 95–102 (2020).
Hilligan, K. L. et al. Pre-existing interferon gamma conditions the lung to mediate early control of SARS-CoV-2. Preprint at bioRxiv https://doi.org/10.1101/2023.07.15.549135 (2023).
Arunachalam, P. S. et al. Systems vaccinology of the BNT162b2 mRNA vaccine in humans. Nature 596, 410–416 (2021).
Li, C. et al. Mechanisms of innate and adaptive immunity to the Pfizer-BioNTech BNT162b2 vaccine. Nat. Immunol. 23, 543–555 (2022).
Pittet, L. F. et al. Randomized trial of BCG vaccine to protect against Covid-19 in health care workers. N. Engl. J. Med. 388, 1582–1596 (2023).
Bruxvoort, K. J. et al. Recombinant adjuvanted zoster vaccine and reduced risk of coronavirus disease 2019 diagnosis and hospitalization in older adults. J. Inf. Dis. 225, 1915–1922 (2022).
Usher, A. D. CEPI launches 100-day vaccine ‘moonshot’. Lancet 399, 1107–1108 (2022).
Acknowledgements
I thank the National Institutes of Health, the Bill and Melinda Gates Foundation, Open Philanthropy, and other anonymous donors for their generous support of the work in my laboratory at Stanford.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The author declares no competing interests.
Rights and permissions
About this article
Cite this article
Pulendran, B. Integrated organ immunity: a path to a universal vaccine. Nat Rev Immunol 24, 81–82 (2024). https://doi.org/10.1038/s41577-024-00990-1
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41577-024-00990-1