Engineering Skin Bacteria for Needle-Free Topical Vaccination

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Event details

Date 15.12.2025
Hour 09:0010:00
Speaker Djenet Bousbaine, Ph.D., Stanford University, CA (USA)
Location Online
Category Conferences - Seminars
Event Language English
3-DAY BIOE MINI-SYMPOSIUM on Life Science Engineering
(DAY TWO:  talk two / previous talk / next talk)

Abstract:
The ubiquitous skin colonist Staphylococcus epidermidis elicits a CD8+ T cell response pre-emptively, in the absence of an infection. However, the scope and purpose of this anti-commensal immune program are not well defined, limiting our ability to harness it therapeutically. Here, we show that this colonist also induces a potent, durable, and specific antibody response that is conserved in humans and non-human primates. A series of S. epidermidis cell-wall mutants revealed that the cell surface protein Aap is a predominant target. By colonizing mice with a strain of S. epidermidis in which the parallel β-helix domain of Aap is replaced by tetanus toxin fragment C, we elicit a potent neutralizing antibody response that protects mice against a lethal challenge. A similar strain of S. epidermidis expressing a Aap SpyCatcher chimera can be conjugated with recombinant immunogens; the resulting labeled commensal elicits long-lasting high titers of antibody under conditions of physiologic colonization, including a robust IgA response in the nasal mucosa. By developing an enzymatic approach to display immunogens on the surface of gram-positive bacteria, we broadened our engineering strategy to encompass members of the microbiome not amenable to genetic manipulation; colonization with the genetically intractable skin microbe Cutibacterium acnes labeled with immunogens using this method elicits potent T and B cell responses. Thus, immunity to a common skin colonist involves a coordinated T and B cell response, the latter of which can be redirected against pathogens as a novel form of topical vaccination.

Bio:
Djenet Bousbaine received a BSc and a MSc from EPFL and a PhD from the Massachusetts Institute of Technology. She is currently a postdoctoral fellow at Stanford University in the laboratory of Michael Fischbach. Her research combines bacterial genetics, immunology and biochemistry to probe the molecular interactions between the microbiome and the immune system and leverages new mechanistic insights to develop non-invasive approaches to induce targeted immune responses. Her recent work uncovered B cell responses to skin microbiota, which she used to engineer a skin bacterium into a new modality of topical vaccines.


Zoom link for attending remotely, if needed: https://epfl.zoom.us/j/69216732793

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  • Free

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