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

• 成果类型: Article
• 署名作者: Bousbaine, Djenet; Bauman, Katherine D.; Chen, Y. Erin; Lalgudi, Pranav V.; Nguyen, Tam T. D.; Swenson, Joyce M.; Yu, Victor K.; Tsang, Eunice; Conlan, Sean; Li, David B.; Jbara, Amina; Zhao, Aishan; Naziripour, Arash; Veinbachs, Alessandra; Lee, Yu E.; Phung, Jennie L.; Dimas, Alex; Jain, Sunit; Meng, Xiandong; Pham, Thi Phuong Thao; Mclaughlin, Martin I.; Barkal, Layla J.; Gribonika, Inta; Van Rompay, Koen K. A.; Kong, Heidi H.; Segre, Julia A.; Belkaid, Yasmine; Barnes, Christopher O.; Fischbach, Michael A.
• 署名单位: Stanford University; Stanford University; Stanford University; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); Stanford University; Chan Zuckerberg Initiative (CZI); Stanford University; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); University of California System; University of California Davis; University of California System; University of California Davis; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS)
• 刊物名称: Nature
• ISSN/ISSBN: 0028-2108
• DOI: 10.1038/s41586-024-08489-4
• 发表日期: 2025-02-27
• 关键词: staphylococcus-epidermidis; tetanus toxin; intercellular-adhesion; immune-responses; mucosal delivery; fragment c; protein; aureus; surface; accumulation

摘要

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 beta-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.