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

Abstract

ABSTRACTThe ubiquitous skin colonistStaphylococcus epidermidiselicits 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 ofS. epidermidiscell-wall mutants revealed that the cell surface protein Aap is a predominant target. By colonizing mice with a strain ofS. epidermidisin 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 ofS. epidermidisexpressing an Aap-SpyCatcher chimera can be conjugated with recombinant immunogens; the resulting labeled commensal elicits high titers of antibody under conditions of physiologic colonization, including a robust IgA response in the nasal 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.