Thi Phuong Thao Pham

All Publications

• Discovery and engineering of the antibody response to a prominent skin commensal. Nature Bousbaine, D., Bauman, K. D., Chen, Y. E., Lalgudi, P. V., Nguyen, T. T., Swenson, J. M., Yu, V. K., Tsang, E., Conlan, S., Li, D. B., Jbara, A., Zhao, A., Naziripour, A., Veinbachs, A., Lee, Y. E., Phung, J. L., Dimas, A., Jain, S., Meng, X., Pham, T. P., McLaughlin, M. I., Barkal, L. J., Gribonika, I., Van Rompay, K. K., Kong, H. H., Segre, J. A., Belkaid, Y., Barnes, C. O., Fischbach, M. A. 2024

  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 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 an Aap-SpyCatcher chimera can be conjugated with recombinant immunogens; the resulting labeled commensal elicits high antibody titers 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 novel form of topical vaccination.

  View details for DOI 10.1038/s41586-024-08489-4

  View details for PubMedID 39662508