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

Bousbaine, Djenet ; Bauman, Katherine D ; Chen, Y Erin ; Lalgudi, Pranav V ; Nguyen, Tam T D LU ; Swenson, Joyce M ; Yu, Victor K ; Tsang, Eunice ; Conlan, Sean and Li, David B , et al. (2025) In Nature 638(8052). p.1054-1064
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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animals, Female, Humans, Male, Mice, Antibodies, Bacterial/immunology, Antibodies, Neutralizing/immunology, Antibody Formation, B-Lymphocytes/immunology, Bacterial Proteins/immunology, CD8-Positive T-Lymphocytes/immunology, Immunoglobulin A/immunology, Mice, Inbred C57BL, Skin/microbiology, Staphylococcus epidermidis/immunology, Symbiosis/immunology, Tetanus Toxin/immunology
in
Nature
volume
638
issue
8052
pages
1054 - 1064
publisher
Nature Publishing Group
external identifiers
  • scopus:85212467426
  • pmid:39662508
ISSN
0028-0836
DOI
10.1038/s41586-024-08489-4
language
English
LU publication?
no
additional info
© 2024. The Author(s), under exclusive licence to Springer Nature Limited.
id
64a1eab9-e9b8-4b89-a94b-344d414aac66
date added to LUP
2025-12-20 13:18:49
date last changed
2025-12-22 15:06:35
@article{64a1eab9-e9b8-4b89-a94b-344d414aac66,
  abstract     = {{<p>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.</p>}},
  author       = {{Bousbaine, Djenet and Bauman, Katherine D and Chen, Y Erin and Lalgudi, Pranav V and Nguyen, Tam T D and Swenson, Joyce M and Yu, Victor K and Tsang, Eunice and Conlan, Sean and Li, David B and Jbara, Amina and Zhao, Aishan and Naziripour, Arash and Veinbachs, Alessandra and Lee, Yu E and Phung, Jennie L and Dimas, Alex and Jain, Sunit and Meng, Xiandong and Pham, Thi Phuong Thao and McLaughlin, Martin I and Barkal, Layla J and Gribonika, Inta and Van Rompay, Koen K A and Kong, Heidi H and Segre, Julia A and Belkaid, Yasmine and Barnes, Christopher O and Fischbach, Michael A}},
  issn         = {{0028-0836}},
  keywords     = {{Animals; Female; Humans; Male; Mice; Antibodies, Bacterial/immunology; Antibodies, Neutralizing/immunology; Antibody Formation; B-Lymphocytes/immunology; Bacterial Proteins/immunology; CD8-Positive T-Lymphocytes/immunology; Immunoglobulin A/immunology; Mice, Inbred C57BL; Skin/microbiology; Staphylococcus epidermidis/immunology; Symbiosis/immunology; Tetanus Toxin/immunology}},
  language     = {{eng}},
  number       = {{8052}},
  pages        = {{1054--1064}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature}},
  title        = {{Discovery and engineering of the antibody response to a prominent skin commensal}},
  url          = {{http://dx.doi.org/10.1038/s41586-024-08489-4}},
  doi          = {{10.1038/s41586-024-08489-4}},
  volume       = {{638}},
  year         = {{2025}},
}