Immune response in nasopharynx, lung, and blood elicited by experimental nasal pneumococcal vaccines containing live or heat-killed lactobacilli as mucosal adjuvants

Abstract

This work analyzes the humoral and cellular immune responses induced by live (LcV) and heat-killed (LcM) Lactobacillus casei associated with the pneumococcal antigen (P-Ag) at the nasopharynx level, considering nasal-associated lymphoid tissue (NALT) as the primary inductive site of the mucosal immune system, and lung and blood as effector sites. Levels of P-Ag IgA and IgG antibodies, main types of B and T cells, and cytokines in mucosal and systemic compartments were evaluated. The results showed that both LcM+P-Ag and LcV+P-Ag vaccines effectively induced IgA and IgG anti-P-Ag Abs in the upper and lower respiratory tract and plasma. These results correlated with increased IgA+ cells in NALT and lung that was induced by the experimental vaccines. Moreover, numbers of IgG+ cells increased in the blood. Profiles of inflammatory and regulatory cytokines were evaluated and their possible implications for the defense against pneumococci was assessed. Considering the overall results, the potential mechanisms of immune stimulation induced by LcM and LcV used as adjuvants are discussed. LcV and LcM showed similar effects on the immune system. Strain viability is not crucial for the stimulation of the antigen-specific immune response, and LcM is a convenient and effective mucosal adjuvant.

Safety of a nasal vaccine against Streptococcus pneumoniae using heat-killed Lactobacillus casei as adjuvant

“…In addition, increased lymphocytes and its participation in the innate immune response would be mainly mediated by IgA+ B cells. In this regard, several studies have shown that certain strains of lactic acid bacteria, including L. casei used in this work, tend to increment mucosal's IgA+ cells (Vinti ñi and Medina, 2014;Maldonado Galdeano et al, 2011;Perdigón et al, 1999), thus raising the levels of secretory IgA. The bind between IgA and S. pneumoniae minimizes the entry of the latter into the body by immune exclusion.…”

“…Thus, lymphocyte increase induced by LcM + PppA would be associated to its movement from the nasopharynx-associated lymphoid tissue (NALT) (Vinti ñi and Medina, 2014) as a result of both direct stimulation and the migration of circulating lymphocytes. Previous studies demonstrated that LcM + PppA induces an activation of T lymphocytes cell population and also an increase of IgA and IgG specific for the antigen (Vinti ñi and Medina, 2011Medina, , 2014 in nasal lavages, bronchoalveolar lavages and serum. On this basis, the increment of lymphocyte population in LBA would be due to the presence of T and B lymphocytes specific for Ag.…”

Elucidating the Immune-Related Mechanisms by Which Probiotic Strain Lactobacillus casei BL23 Displays Anti-tumoral Properties

“…Surprisingly, we failed to locate administered bacteria in BAL samples as previously described for other LAB (Grangette et al, 2001), however, in that study, their analyses were performed later (10 days after instillation) and we cannot exclude that we examined bacterial location too early for BAL detection. However, NALT has been described as an important tissue not only for mucosal but also for systemic immune response stimulation (Vintini and Medina, 2014) (Medaglini et al, 2006). Indeed, Vintini et al reported a specific T-cell response after administration of another L. casei strain in NALT and serum samples.…”

New Developments in Oral Vaccines and Mucosal Adjuvants

“…It is considered that other bacteria would also be suitable as adjuvants, such as L. casei, L. plantarum, L. rhamnosus and Bifidobacterium breve. Recent work has shown that both live and heat-killed Lactobacillus casei, associated with pneumococcal antigen (P-Ag) are effective mucosal adjuvants at the nasopharynx level, inducing IgA and IgG anti-P-Ag Abs in the upper and lower respiratory tract [20].…”