Abstract

Non-viable lactic acid bacteria (LAB) have been proposed as antigen delivery platforms called bacterium-like particles (BLPs). Most studies have been performed with Lactococcus lactis-derived BLPs where multiple antigens were attached to the peptidoglycan surface and used to successfully induce specific immune responses. It is well-established that the immunomodulatory properties of LAB are strain dependent and therefore, the BLPs derived from each individual strain could have different adjuvant capacities. In this work, we obtained BLPs from immunomodulatory (immunobiotics) and non-immunomodulatory Lactobacillus rhamnosus and Lactobacillus plantarum strains and comparatively evaluated their ability to improve the intestinal and systemic immune responses elicited by an attenuated rotavirus vaccine. Results demonstrated that orally administered BLPs from non-immunomodulatory strains did not induce significant changes in the immune response triggered by rotavirus vaccine in mice. On the contrary, BLPs derived from immunobiotic lactobacilli were able to improve the levels of anti-rotavirus intestinal IgA and serum IgG, the numbers of CD24+B220+ B and CD4+ T cells in Peyer's patches and spleen as well as the production of IFN-γ by immune cells. Interestingly, among immunobiotics-derived BLPs, those obtained from L. rhamnosus CRL1505 and L. rhamnosus IBL027 enhanced more efficiently the intestinal and systemic humoral immune responses when compared to BLPs from other immunobiotic bacteria. The findings of this work indicate that it is necessary to perform an appropriate selection of BLPs in order to find those with the most efficient adjuvant properties. We propose the term Immunobiotic-like particles (IBLPs) for the BLPs derived from CRL1505 and IBL027 strains that are an excellent alternative for the development of mucosal vaccines.

Highlights

  • Lactic acid bacteria (LAB) have been studied for several years as potential delivery systems and/or adjuvants for mucosal vaccine development

  • We demonstrated that Immunobiotic-like particles (IBLPs) derived from highly efficient immunomodulatory lactobacilli are an interesting alternative as mucosal adjuvants

  • It has been proposed that the final outcome of a host cell response against beneficial immunomodulatory microorganisms depends on the combination of distinct microbial-associated molecular patterns (MAMPs) that can interact with various pattern recognition receptors (PRRs) and associated co-receptors to trigger different signaling pathways [20, 21]

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Summary

Introduction

Lactic acid bacteria (LAB) have been studied for several years as potential delivery systems and/or adjuvants for mucosal vaccine development In this regard, recombinant LAB expressing pathogen’s antigens in their cell-walls have been used as oral or nasal vaccines in animal models [1,2,3,4]. An original alternative to the use of genetically modified LAB was the development of bacterium-like particles (BLPs) derived from the acid and heat treatments of Lactococcus lactis [5,6,7,8]. The microbial pathogens tested in those investigations included bacteria, parasites and viruses such as Streptococcus pneumoniae [5], Plasmodium berghei [7, 9], and Influenza virus [10] Those studies clearly demonstrated that L. lactis-derived BLPs are a promising adjuvant for mucosal immunization

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