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Could a “Tailored” Vaccine Be the Key to Treating Eczema in Children

A healthcare provider placing a bandage on the injection site of a child who had just received a vaccination
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At Trinity College Dublin, a group of multi-disciplinary researchers including Dr. Rachel McLoughlin, professor of immunology are exploring how children's immune systems respond to flares of eczema driven by the Staphylococcus aureus (S. aureus) bacterium.

Eczema (also known as atopic dermatitis (AD)) is estimated to affect 15–20% of children globally. Symptoms can include persistent itchy skin, sleeping issues and stigma around having visible rashes. The presence of bacteria can lead to weeping wounds that can progress to more severe infections.

In their JCI Insight study, McLoughlin and team uncovered important immune signatures in children with infected flares of eczema. Pinpointing these signatures provides specific new targets for therapies.

In an interview with Technology Networks, McLoughlin discusses how the immune system is altered in those with infected eczema flares and how these findings may be used to inform tailored vaccines for bacteria-triggered eczema flare-ups.

Blake Forman (BF): Why is a tailored vaccine an attractive target for treating and preventing infected flares of eczema?

Rachel McLoughlin (RM): Current treatments in the clinical setting target the downstream effects of S. aureus in eczema, using either antibiotics or immunomodulatory medications. Antimicrobial resistance however is a growing threat and alternative antimicrobial strategies, including vaccine development, are vital to counteract this.

A vaccine against S. aureus would have the potential not only to eliminate S. aureus-mediated flares of AD, but could also limit the development of atopic diseases, which include eczema, hay fever, asthma and food allergy.

BF: Can you summarize your findings on how the immune response was impacted in those with infected eczema flares?

RM: This study illustrates a pattern of host systemic immunosuppression associated with infected flares of eczema manifesting as lower numbers of circulating Th1, CD4+, CD8+ and S. aureus antigen-specific memory IL10, ex Th17 cells and skin-homing CLA+ Th17 cells, all of which are involved in protective systemic responses to S. aureus infection.

In contrast, expansion of Th2, memory Th2 and CLA+ Th2 responses were observed, favoring the persistence of S. aureus and its downstream deleterious effects on cutaneous inflammation.

Expansion of Vδ1 and Vδ2 γδ T cell subsets in infected flares of eczema was also observed. Vδ2 expansion in this study is hypothesized to represent a host protective mechanism to counteract the immunosuppressive effects of S. aureus on conventional T cell subsets. Clonally expanded γδ T cells may represent a potential mechanism for long-lasting immunity against recurrent S. aureus skin infections and alongside targeting Th17 responses, should be considered important components of protective immunity to be targeted in future vaccine design.

The findings highlight the importance of ensuring an appropriate balance of T cell subsets, to counteract the effects of S. aureus in AD.

BF: What steps are necessary to transition these findings from research to the clinic?

RM: An effective future S. aureus vaccine will need to expand on the interrogation of T cell responses in this study and comprise both B and T cell activating epitopes. Identifying the most appropriate B and T cell epitopes is essential to prevent non-protective immune imprinting, which can impact future vaccine responses to infection.

Tissue-resident memory (Trm), Vδ1 and Vδ2 γδ T cell subsets warrant further investigation to identify their specific roles and utility as vaccine targets.

Vaccines targeting specific T cell subsets, including Th17, will need to be assessed across a broad spectrum of patients with varying genotypes and endotypes of eczema to ensure balanced activation of T cell subsets, ultimately improving disease outcomes.

BF: What are the next steps for this research?

RM: This research identifies important T cell immune signatures associated with S. aureus infected flares of eczema, which can help inform future vaccine targets. 

The development of effective vaccines necessitates that appropriate correlates of immunity are first identified i.e., it is necessary to identify what mode of immunity needs to be induced to render a vaccine effective. Understanding the immune phenotypes in relevant patient cohorts is necessary to identify appropriate correlates of immunity.

Overall, this work's future directions include expanding to a larger patient cohort over a prolonged time course, with greater ethnic diversity and age range, and stratifying patient cohorts according to age profiles, genotypic and endotypic features. This is essential to identify heterogenous responses, which may impact vaccine therapeutic responses. It will also be important to investigate S. aureus specific CD4+ skin Trm cells, which are likely to play a substantive role in mediating local cutaneous responses to S. aureus in AD.

Dr. Rachel McLoughlin was speaking to Blake Forman, Senior Science Writer & Editor for Technology Networks.

About the interviewee:

Dr. Rachel McLoughlin is a professor of immunology at Trinity College Dublin. She earned her PhD in immunology from the University of Cardiff. Her research interests include the study of skin delivery and tissue-resident T cell responses for novel vaccine development.

Reference: Clowry J, Dempsey DJ, Claxton TJ, et al. Distinct T cell signatures are associated with Staphylococcus aureus skin infection in pediatric atopic dermatitis. JCI Insight. 2024;9(9). doi: 10.1172/jci.insight.178789