The normal immune response to harmless gut antigens and commensal bacteria is the induction of a local and systemic immunological tolerance, known as oral tolerance [22] , [23] . Immunological tolerance can be exploited to develop immunotherapies for autoimmune and inflammatory diseases but it is also the obstacle to the development of oral vaccines [23] . As a result of our observation that an oral vaccine based in L. plantarum expressing the OspA lipoprotein induced a protective, IgG-based, immune response in mice [12] we set out to further understand the processes that determine the immunological consequences of oral administration of antigen. We investigated the role of L. plantarum expressing OspA lipoprotein in breaking the oral tolerance of the gut and if this immune response was dependent on the lipid modification of OspA.