Impact of oral probiotic Lactobacillus acidophilus vaccine vactor on the murine gut microbiome

While it is clear that the microbiome greatly influences the state of mucosal health, how it influences, and is influenced by, the mucosal immune response to vaccines is poorly understood. In this study we evaluate the impact of using Lactobacillus acidophilus as a probiotic vaccine vector on the gut microbiome. We have developed a strain of L. acidophilus that expresses the membrane proximal external region (MPER) from HIV-1 within the context of the major S-layer protein A. In addition to MPER expression, two other strains either secrete interleukin-1B or express the surface flagellin subunit C (FliC); in addition to MPER. We observed a differential effect of this vaccine vector that is strain-dependent suggesting that MPER and MPER with secretion of IL-1B induce a shift of the microbiome while MPER with expression of FliC has minimum impact. We also observed a compound effect on the microbiome of the joint use of the probiotic and the prebiotic highlighting the opportunity to use a synbiotic approach to impact efficacy of vaccination. These results suggest that careful consideration of the constitutive adjuvants and use of supplementation is needed depending on whether the target is modulation of the microbiome to improve efficacy of vaccination or maintenance of the resident microbiome. No clear associations were observed between the total and MPER-specific IgA with microbiome change indicating a possible role for other immune mechanisms in driving changes in the microbiome or the need to fine tune our studies to focus on IgA bound, putatively resident microbiota presumably affected by a mucosal immune response. To our knowledge no probiotic vaccine has been tested for gut microbiome alterations, and prior evidence with other oral vectors suggests that oral vaccines do not cause significant perturbations to the host microbiome.