Immunogenicity and Safety of Lactobacilli as Oral Mucosal Vaccine Vectors.

摘要

Lactobacillus sp. are commensal bacteria that have long been utilized as probiotics and are generally regarded as safe (GRAS-status) for use in humans, making them prime candidates for vector design. Recent research has, however, focused on the probiotic properties of commensal bacteria rather than their specific interactions with the mucosal immune system. In order to rationally develop lactobacilli as vaccine vectors, we sought to better define the role of Lactobacillus in immune stimulation and to assess the safety of a Lactobacillus-based vaccine vector in both the immune-compromised and healthy host.;In vitro studies showed, first, that lactobacilli primarily activate Toll-like receptor (TLR) 2/6, with additional activation through TLR2. Co-culture of lactobacilli with human myeloid dendritic cells (DC) led to functional and phenotypic maturation of these cells. In the mucosal immune system, we found that oral L. acidophilus treatment results in diversification of the colonic B cell population. Finally, we showed that L. acidophilus distinctly interacts with the mucosal immune system of the FIV+ and FIV- host, leading to divergent immune responses. These immune responses may be in part due to the actions of FIV in the intestine, resulting in the upregulation of transcellular transport across the mucosal epithelium.