Immunomodulatory Properties of Bacterium-Like Particles Obtained From Immunobiotic Lactobacilli: Prospects for Their Use as Mucosal Adjuvants

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.

The Ability of Respiratory Commensal Bacteria to Beneficially Modulate the Lung Innate Immune Response Is a Strain Dependent Characteristic

“…BLPs derived from immunomodulatory bacteria should be carefully studied to find out if they retain the immunomodulatory properties and if they do, whether or not the effect is similar to that induced by viable bacteria. These findings are in line with our recent study reporting that BLPs from distinct immunomodulatory lactobacilli differs in their capacity to modulate the intestinal immunity [21].…”

“…Bacterium-like particles (BLPs) from C. pseudodiphteriticum 090104 and D. pigrum 040417 were obtained by following the method of [21]. Briefly, bacteria from a fresh overnight culture (100 mL) were collected by centrifugation (10 min, 13,000× g) and washed once with sterile distilled water.…”

Lactiplantibacillus plantarum as a Potential Adjuvant and Delivery System for the Development of SARS-CoV-2 Oral Vaccines

“…Thus, L. plantarum would be capable of stimulating the intestinal adaptive immunity through its ability to modulate antigen presentation in DCs in a type I IFN-dependent manner. Moreover, this hypothesis prompted us to evaluate whether orally administered L. plantarum CRL1506 or its non-viable bacterium-like particles (BLPs) were able to modify the immune response to an oral vaccine [ 108 ]. In our hands, L. plantarum CRL1506 or its BLPs showed adjuvant capacities when used together with a rotavirus vaccine.…”

“…Immunization of mice with L. plantarum CRL1506 or its BLPs significantly improved the specific Th1 mucosal and systemic immune responses generated against the rotavirus antigens. Furthermore, our immunization protocol not only stimulated the cellular immunity but also increased levels of intestinal IgA- and serum IgG-specific antibodies were found in animals immunized with rotavirus vaccine and the CRL1506 strain [ 108 ]. These results provide additional evidence for the hypothesis that gives a key role to type I IFNs in the efficient generation of adaptive responses induced by immunobiotic L. plantarum treatments since it was demonstrated that type I IFNs promote antibody responses in vivo [ 109 ].…”

“…Of note, our and other groups proved that L. plantarum strains had different adjuvant capacities in terms of their ability to improve the intestinal cellular and humoral immune responses triggered by virus infection or vaccination. Both humoral and cellular intestinal specific immune responses were significantly upgraded in mice immunized with rotavirus vaccine and L. plantarum CRL1506 but not in animals treated with L. plantarum CRL1905 or its BLPs, indicating that distinct strains function differently as mucosal adjuvants [ 108 ]. The final outcome of cellular response against beneficial immunomodulatory lactobacilli depends on the combination of different microbial-associated molecular patterns (MAMPs) that can interact with various PRRs to trigger different signaling pathways [ 112 ].…”