Dendritic Cells TargetingLactobacillus plantarumStrain NC8 with a Surface-Displayed Single-Chain Variable Fragment of CD11c Induce an Antigen-Specific Protective Cellular Immune Response

Abstract

Influenza A virus (H1N1) is an acute, highly contagious respiratory virus. The use of lactic acid bacteria (LAB) to deliver mucosal vaccines against influenza virus infection is a research hot spot. In this study, two recombinant Lactobacillus plantarum strains expressing hemagglutinin (HA) alone or coexpressing aCD11c-HA to target HA protein to dendritic cells (DCs) by fusion to an anti-CD11c single-chain antibody (aCD11c) were constructed. The activation of bone marrow dendritic cells (BMDCs) by recombinant strains and the interaction of activated BMDCs and sorted CD4+ or CD8+ T cells were evaluated through flow cytometry in vitro, and cellular supernatants were assessed by using an enzyme-linked immunosorbent assay kit. The results demonstrated that, compared to the HA strain, the aCD11c-HA strain significantly increased the activation of BMDCs and increased the production of CD4+ gamma interferon-positive (IFN-γ+) T cells, CD8+ IFN-γ+ T cells, and IFN-γ in the cell culture supernatant in vitro. Consistent with these results, the aCD11c-HA strain clearly increased the activation and maturation of DCs, the HA-specific responses of CD4+ IFN-γ+ T cells, CD8+ IFN-γ+ T cells, and CD8+ CD107a+ T cells, and the proliferation of T cells in the spleen, finally increasing the levels of specific antibodies and neutralizing antibodies in mice. In addition, the protection of immunized mice was observed after viral infection, as evidenced by improved weight loss, survival, and lung pathology. The adoptive transfer of CD8+ T cells from the aCD11c-HA mice to NOD/Lt-SCID mice resulted in a certain level of protection after influenza virus infection, highlighting the efficacy of the aCD11c targeting strategy.

Homologous Sequential Immunization Using Salmonella Oral Administration Followed by an Intranasal Boost with Ferritin-Based Nanoparticles Enhanced the Humoral Immune Response against H1N1 Influenza Virus

“…A number of bacterial vectors, such as attenuated Salmonella ( 18 ) and probiotic lactic acid bacteria ( 19 ), have been used to deliver protective antigens through an oral immunization approach. In particular, Roy Curtiss III’s lab developed a series of Salmonella strains and vectors with novel features to enhance immunogenicity, including regulated delayed synthesis of heterologous antigens ( 20 ) and regulated delayed attenuation ( 21 ), which provide the vaccine strain with a nearly wild-type ability to colonize lymphoid tissues before exhibiting an attenuated phenotype, thereby leading to the development of strong immune responses.…”

STxB as an Antigen Delivery Tool for Mucosal Vaccination

“…After mucosal administration, LABs and nanoparticles generate mucosal responses against entrapped antigens [ 161 , 162 , 163 , 164 ]. To improve their efficacy, LABs such as lactobacillus have been coupled with DC targeting peptides; alternatively, complement C3d3, anti-CD205, anti-CD11c, or neonatal Fc receptors (FcRn) have been expressed at their surface [ 165 , 166 , 167 , 168 ]. Nanoparticles such as poly(lactic-co-glycolic acid) and liposomes have also been functionalized with anti-DEC-205 [ 169 ], anti-CD40 [ 170 ], anti-mannose receptor [ 171 ], or anti-CD11c [ 172 ] antibodies to target them to DCs.…”

Lactiplantibacillus plantarum attenuates Coxsackievirus B3-induced pancreatitis through the BAX/BCL2/CASP3 signaling pathway

“…16,17 While the underlying mechanisms remain largely unknown, many studies have shown that L. plantarum prevents virus infection and reduces cell inflammation by enhancing innate immunity, regulating gut microbiota, 14,18 inhibiting virus replication, 19,20 and modulating cytokine production. 21 Exopolysaccharides (EPS) produced by LAB have various biological activities. They can protect bacterial cells from environmental effects such as desiccation and heat and acidic stresses.…”

“…16,17 While the underlying mechanisms remain largely unknown, many studies have shown that L. plantarum prevents virus infection and reduces cell inflammation by enhancing innate immunity, regulating gut microbiota, 14,18 inhibiting virus replication, 19,20 and modulating cytokine production. 21…”