Discovery and engineering of the antibody response to a prominent skin commensal

Djenet Bousbaine, Katherine D. Bauman, Y. Erin Chen, Pranav V. Lalgudi, Tam T. D. Nguyen, Joyce M. Swenson, Victor K. Yu, Eunice Tsang, Sean Conlan, David B. Li, Amina Jbara, Aishan Zhao, Arash Naziripour, Alessandra Veinbachs, Yu E. Lee, Jennie L. Phung, Alex Dimas, Sunit Jain, Xiandong Meng, Thi Phuong Thao Pham, Martin I. McLaughlin, Layla J. Barkal, Inta Gribonika, Koen K. A. Van Rompay, Heidi H. Kong, Julia A. Segre, Yasmine Belkaid, Christopher O. Barnes and Michael A. Fischbach ()
Additional contact information
Djenet Bousbaine: Stanford University
Katherine D. Bauman: Stanford University
Y. Erin Chen: Stanford University
Pranav V. Lalgudi: Stanford University
Tam T. D. Nguyen: Stanford University
Joyce M. Swenson: Stanford University
Victor K. Yu: Stanford University
Eunice Tsang: Stanford University
Sean Conlan: National Institutes of Health
David B. Li: Stanford University
Amina Jbara: Stanford University
Aishan Zhao: Stanford University
Arash Naziripour: Stanford University
Alessandra Veinbachs: Stanford University
Yu E. Lee: Stanford University
Jennie L. Phung: Stanford University
Alex Dimas: Stanford University
Sunit Jain: Chan Zuckerberg Biohub
Xiandong Meng: Stanford University
Thi Phuong Thao Pham: Stanford University
Martin I. McLaughlin: Stanford University
Layla J. Barkal: Stanford University
Inta Gribonika: National Institutes of Health
Koen K. A. Van Rompay: University of California
Heidi H. Kong: National Institutes of Health
Julia A. Segre: National Institutes of Health
Yasmine Belkaid: National Institutes of Health
Christopher O. Barnes: Stanford University
Michael A. Fischbach: Stanford University

Nature, 2025, vol. 638, issue 8052, 1054-1064

Abstract: Abstract The ubiquitous skin colonist Staphylococcus epidermidis elicits a CD8+ T cell response pre-emptively, in the absence of an infection1. However, the scope and purpose of this anticommensal immune programme 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 an Aap-SpyCatcher chimera can be conjugated with recombinant immunogens; the resulting labelled commensal elicits high antibody titres under conditions of physiologic colonization, including a robust IgA response in the nasal and pulmonary mucosa. 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 new form of topical vaccination.

Date: 2025
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DOI: 10.1038/s41586-024-08489-4

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