Oral vaccination using a probiotic vaccine platform combined with prebiotics impacts immune response and the microbiome

Development of oral vaccination strategies remains a priority to address needs in low and middle income countries where cost, logistics of distribution, and low efficacy of existing vaccines remain obstacles to successful vaccination of the global population. Probiotics, specifically lactic acid bacteria, have emerged as an intriguing platform for oral vaccines due to their immunomodulatory properties, ability to persist in the gut, low cost, and stability at ambient temperatures. It has been clearly demonstrated that intestinal microbiome influences vaccine immunogenicity and the use of a probiotic platform raised the prospect contributing to either positive or negative effects on the microbial community structure. In addition to effects on the whole microbiome, induction of mucosal IgA by Lactobacillus species might also influence which members of the microbiome are coated by IgA. Combining a probiotic vaccine with a prebiotic might also influence both the efficacy of the vaccine and composition of the microbiome. In this study, a recombinant Lactobacillus acidophilus strain GAD19, which expresses a peptide from human immunodeficiency virus type 1 and secrets murine interleukin-1b as an adjuvant, was used to orally immunize mice. A rice bran diet was also tested as a rational prebiotic strategy. We show that IgA-bound bacteria were not disproportionately affected by perturbations due to vaccination and alpha diversity of the gut microbiome was not affected by vaccination or diet. The rice bran diet did play a primary role in differences observed in beta-diversity community structure and resulted in a more rapid induction of antigen-specific antibodies. Minor changes in the microbiome were associated with the presence of the probiotic L. acidophilus rather than the vaccine strain per se. Collectively, our results demonstrate that rLA does not cause long-term alterations to the microbiome, and the bacterial microbiome coated with IgA is also able to recover to a pre-vaccination state. This work reduces concerns that rLA has a long-term impact on the intestinal microbiome and raises the opportunity to improve mucosal immune responses against antigens expressed by rLA in combination with rice bran as a prebiotic.