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A network of protection across tissues drives vaccine efficiency

von Cornelius C. Thaiss

A fundamental conundrum underlying vaccination is that most vaccines are administered to the skin, while the actual infection occurs at mucosal surfaces, such as the respiratory or gastrointestinal tract. Immune responses are typically carried out in a local fashion, in order to restrict inflammation to the site where it is effective in eliminating the pathogen while avoiding tissue damage in other organs.

How then is a protective immune response by vaccination in one tissue delivered to a different one? We have used a comparative infection model together with a systems biology approach to answer this question.

We have observed immune signal propagation between organs and have obtained a dynamic map of immune processes at the organism level. Using this approach, we have uncovered two inter-organ mechanisms of protective immunity mediated by soluble and cellular factors that act at different time scales (Figure 1): First, analyzing ligand-receptor connectivity across tissues revealed that type I interferons trigger a whole-body antiviral state, protecting the host within hours after skin vaccination. Second, combining parabiosis, single-cell analyses, and gene knockouts, we uncovered a multi-organ web of tissue-resident memory T cells that functionally adapt to their environment to stop viral spread across the organism over the course of several days.

These results provide new insights into the mechanisms by which protective immunity is spread from the site of vaccination to different tissues via the innate and adaptive immune system. In addition, our findings have implications for manipulating tissue-resident cells through vaccination and open up new lines of inquiry for the analysis of immune responses at the organism level [1].



[1]  Kadoki M, Patil A, Thaiss CC, Brooks DJ, Pandey S, Deep D, Alvarez D, von Andrian UH, Wagers  AJ, Nakai K, Mikkelsen TS, Soumillon M, Chevrier N. 2017. Organism-Level Analysis of Vaccination Reveals Networks of Protection across Tissues. Cell 171: 398-413 e21



About the person:

Cornelius C. Thaiss studies medicine at the Ludwig-Maximilians-Universität München (LMU) and technology management at the Center for Digital Technology and Management (CDTM), a joint institution of the LMU and the Technical University of Munich with a focus on innovation, product development and entrepreneurship.
For his doctoral studies, he joined the group of Dr. Nicolas Chevrier at the Center for Systems Biology of the Faculty of Arts and Sciences at Harvard University in Boston, USA.



Figure 1. Dissemination of skin vaccine-induced protection throughout the organism. Vaccination in the skin triggers a whole-organism antiviral gene expression program, which protects from systemic viral challenge within hours after vaccination. In addition, memory T cells circulate throughout the body to become tissue-resident and protect potential target tissues of the virus from infection.

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