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Potential vaccine targets identified for pediatric AD



Photo by: Jason Pratt via Flickr

New research suggests a “tailored vaccine” might hold the key to treating bacteria-driven atopic dermatitis (AD) flares in children.


“There is a real need for new options to treat and prevent infected flares of eczema in children. Current strategies are limited in their success and—even when they do provide relief—the effects may be short-term as symptoms often return,” said the study’s lead author Julianne Clowry, MD, in a press release. “Although antibiotics are needed in some cases, scientists are trying hard to deliver alternative options due to the growing problems posed by antimicrobial resistance.” Dr. Clowry is a Consultant Dermatologist and Visiting Research Fellow at Trinity College Dublin.


Dr. Clowry said a tailored vaccine is an attractive research target that could effectively limit AD severity, lead to improved and longer-lasting outcomes, reduce the need for antibiotics, and reduce the risk of complications or progression of the atopic march.


In the study, published in JCI Insight (May 8, 2024; 9(9):e178789), researchers compared immune responses in 93 children aged zero to 16 years, divided into three groups: those with both AD and a confirmed S. aureus skin infection, AD but no S. aureus skin infection, and a healthy group of volunteers.  

  

The researchers identified immune signatures in children with infected flares of AD. These signatures represent potential targets for vaccine design.


Importantly, investigators found the proportions of certain T cells, as well as other biomarkers, varied considerably in the different groups.


Specifically, the immune signature related to S. aureus skin infection (ADS.aureus) was most highly associated with elevated cutaneous chemokines IP10 and TARC, which preferentially direct T-helper (Th)1 and Th2 cells to the skin. Systemic CD4+ and CD8+ T cells, except for Th2 cells, were suppressed in ADS.aureus, particularly circulating Th1, memory IL-10+ T cells, and skin-homing memory Th17 cells. The authors also observed systemic γδ T cell expansion in ADS.aureus.


The authors say their findings highlight that the immune response was impacted in those with infected flares of eczema—with the suppression of some of the important T cells that drive an effective immune response. “These findings provide an early blueprint in developing future therapies which could provide targeted effective relief from recurrent flares of eczema,” they write.


Alan Irvine, MD, DSc, Professor of Dermatology at Trinity, and an author of the paper said: “While an interaction between the Staphylococcus aureus bug and eczema has been known for many decades, novel scientific approaches are continuing to make key discoveries about the complex relationship between these bacteria and human responses to it. Our work outlines new discoveries about how children with eczema respond immunologically to infection with this common bacterium.”


Rachel McLoughlin, PhD, Professor in Immunology at Trinity and senior author on the study, added: “This work has identified an overall pattern of immune suppression associated with infected flares of eczema, which results in the suppression of specific T cells that are vital to help initiate an effective immune response. Further work is now required to broaden the scope of these results, by expanding to a larger number of people. This will help confirm if the patterns identified are consistent among different age groups, and in sub-groups with greater ethnic diversity.


“We believe that a more comprehensive understanding of the immune response to this bacteria S. aureus in eczema has significant potential to revolutionize treatment approaches and make a major translational impact in the management of eczema.”

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