Lactobacillus plantarum surface-displayed ASFV (p54) with porcine IL-21 generally stimulates protective immune responses in mice.
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ABSTRACT:
SUBMITTER: Chen XL
PROVIDER: S-EPMC8360262 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:A significant correlation is observed between Fusobacterium nucleatum (F. nucleatum) and the evolution of inflammatory bowel disease (IBD). Particularly, FomA, a critical pathogenic element of F. nucleatum, inflicts substantial detriment to human intestinal health. Our research focused on the development of recombinant Lactobacillus plantarum that expresses FomA protein, demonstrating its potential in protecting mice from severe IBD induced by F. nucleatum. To commence, two recombinant strains, namely L. plantarum NC8-pSIP409-pgsA'-FomA and NC8-pSIP409-FnBPA-pgsA'-FomA, were successfully developed. Validation of the results was achieved through flow cytometry, ELISA, and MTT assays. It was observed that recombinant L. plantarum instigated mouse-specific humoral immunity and elicited mucosal and T cell-mediated immune responses. Significantly, it amplified the immune reaction of B cells and CD4+T cells, facilitated the secretion of cytokines such as IgA, IL4, and IL10, and induced lymphocyte proliferation in response to FomA protein stimulation. Finally, we discovered that administering recombinant L. plantarum could protect mice from severe IBD triggered by F. nucleatum, subsequently reducing pathological alterations and inflammatory responses. These empirical findings further the study of an innovative oral recombinant Lactobacillus vaccine.
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Project description:African Swine Fever Virus (ASFV) has spread worldwide, and the lack of vaccines severely negatively impacts the pig industry. In this study, the p14.5 protein encoded by ASFV was used as the antigen, and the p14.5 gene was expressed in vitro using the Lactobacillus expression system. Three new functionally recombinant Lactobacillus plantarum (L. plantarum) were constructed and the expressions of the p14.5 protein, p14.5-IL-33-Mus fusion protein and CTA1-p14.5-D-D fusion protein were successfully detected using Western blot analysis. After oral immunization of SPF mice with recombinant L. plantarum, flow cytometry and ELISA were performed to detect the differentiation and maturity of T lymphocytes, B lymphocytes and DCs of the mice, which were higher than those of the control group. Specific antibodies were produced. The immunogenicity of the adjuvant group was stronger than that of the single antigen group, and the IL-33 adjuvant effect was stronger than that of the CTA1-DD adjuvant.
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Project description:Interferon (IFN)-λ plays an essential role in mucosal cells which exhibit strong antiviral activity. Lactobacillus plantarum (L. plantarum) has substantial application potential in the food and medical industries because of its probiotic properties. Alphacoronaviruses, especially porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV), cause high morbidity and mortality in piglets resulting in economic loss. Co-infection by these two viruses is becoming increasingly frequent. Therefore, it is particularly important to develop a new drug to prevent diarrhea infected with mixed viruses in piglets. In this study, we first constructed an anchored expression vector with CWA (C-terminal cell wall anchor) on L. plantarum. Second, we constructed two recombinant L. plantarum strains that anchored IFN-λ3 via pgsA (N-terminal transmembrane anchor) and CWA. Third, we demonstrated that both recombinant strains possess strong antiviral effects against coronavirus infection in the intestinal porcine epithelial cell line J2 (IPEC-J2). However, recombinant L. plantarum with the CWA anchor exhibited a more powerful antiviral effect than recombinant L. plantarum with pgsA. Consistent with this finding, Lb.plantarum-pSIP-409-IFN-λ3-CWA enhanced the expression levels of IFN-stimulated genes (ISGs) (ISG15, OASL, and Mx1) in IPEC-J2 cells more than did recombinant Lb.plantarum-pSIP-409-pgsA'-IFN-λ3. Our study verifies that recombinant L. plantarum inhibits PEDV and TGEV infection in IPEC-J2 cells, which may offer great potential for use as a novel oral antiviral agent in therapeutic applications for combating porcine epidemic diarrhea and transmissible gastroenteritis. This study is the first to show that recombinant L. plantarum suppresses PEDV and TGEV infection of IPEC-J2 cells.
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Project description:BACKGROUND:Avian coccidiosis posts a severe threat to poultry production. In addition to commercial attenuated vaccines, other strategies to combat coccidiosis are urgently needed. Lactobacillus plantarum has been frequently used for expression of foreign proteins as an oral vaccine delivery system using traditional erythromycin resistance gene (erm). However, antibiotic selection markers were often used during protein expression and they pose a risk of transferring antibiotic resistance genes to the environment, and significantly restricting the application in field production. Therefore, a food-grade recombinant L. plantarum vaccine candidate would dramatically improve its application potential in the poultry industry. RESULTS:In this study, we firstly replaced the erythromycin resistance gene (erm) of the pLp_1261Inv-derived expression vector with a non-antibiotic, asd-alr fusion gene, yielding a series of non-antibiotic and reliable, food grade expression vectors. In addition, we designed a dual-expression vector that displayed two foreign proteins on the surface of L. plantarum using the anchoring sequences from either a truncated poly-γ-glutamic acid synthetase A (pgsA') from Bacillus subtilis or the L. acidophilus surface layer protein (SlpA). EGFP and mCherry were used as marker proteins to evaluate the surface displayed properties of recombinant L. plantarum strains and were inspected by western blot, flow cytometry and fluorescence microscopy. To further determine its application as oral vaccine candidate, the AMA1 and EtMIC2 genes of E. tenella were anchored on the surface of L. plantarum strain. After oral immunization in chickens, the recombinant L. plantarum strain was able to induce antigen specific humoral, mucosal, and T cell-mediated immune responses, providing efficient protection against coccidiosis challenge. CONCLUSIONS:The novel constructed food grade recombinant L. plantarum strain with double surface displayed antigens provides a potential efficient oral vaccine candidate for coccidiosis.
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Project description:To investigate the effects of Lactobacillus plantarum (L. plantarum) CAI6 and L. plantarum SC4 on hyperlipidemic mice.Male Kunming mice were fed a high-cholesterol diet for 28 d to construct hyperlipidemic models. Hyperlipidemic mice and normal mice were assigned to 3 groups which were separately treated with L. plantarum CAI6, L. plantarum SC4, and physiological saline through oral gavage for 28 d. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured by commercially available enzyme kits. FACS Calibur flow cytometry was used to examine hepatic and renal nuclear factor-erythroid 2-related factor 2 (Nrf2) expression. The morphology of livers was checked by hematoxylin and eosin staining and optical microscope observation.Compared with normal mice, hyperlipidemic mice possessed significantly higher TC (3.50 ± 0.43 vs 2.89 ± 0.36, P < 0.01), TG (1.76 ± 0.07 vs 1.10 ± 0.16, P < 0.01), and LDL-C (1.72 ± 0.20 vs 0.82 ± 0.10, P< 0.01) levels, resulting in an increase of atherogenic index (AI) (2.34 ± 1.60 vs 0.93 ± 0.55, P < 0.05) and LDL-C/HDL-C ratio (1.43 ± 0.12 vs 0.51 ± 0.16, P < 0.05). After treatment with L. plantarum CAI6/L. plantarum SC4, TG (1.43 ± 0.27/1.54 ± 0.10 vs 1.76 ± 0.07, P < 0.01/P < 0.05) and LDL-C (1.42 ± 0.07/1.47 ± 0.12 vs 1.72 ± 0.20, P < 0.01/P < 0.01) in hyperlipidemic mice significantly decreased. In addition, TC, HDL-C, AI, and LDL-C/HDL-C ratio were all positively changed. Meanwhile, the treatment markedly alleviated hepatic steatosis and significantly stimulated Nrf2 expression (73.79 ± 0.80/72.96 ± 1.22 vs 54.94 ± 1.84, P < 0.01/P < 0.01) in hepatocytes of hyperlipidemic mice.L. plantarum CAI6 and L. plantarum SC4 may protect against cardiovascular disease by lipid metabolism regulation and Nrf2-induced antioxidative defense in hyperlipidemic mice.
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Project description:African swine fever virus (ASFV) is a highly lethal pathogen of domestic and wild pigs. Due to no vaccines or drugs available, early accurate diagnosis and eradication of infected animals are the most important measures for ASFV prevention and control. Bluetongue virus (BTV) core-like particles (CLPs) are non-infectious hollow nanoparticles assembled from the BTV VP3 and VP7 proteins, which could be used as a platform for presenting foreign epitopes. In this study, the secondary structure of BTV VP7 protein was analyzed and predicted using the IEDB Analysis resource. Based on the prediction results of the VP7 protein, the chimeric CLPs with an ASFV P54 epitope were successfully prepared through the BAC-to-BAC baculovirus expression system and sucrose gradient centrifugation. Based on the chimeric CLPs and mAb 2E4 against AFSV P54 epitope, a blocking ELISA for detecting AFSV antibodies was established, and its reaction conditions were optimized. Through comprehensive evaluation of the method, the results showed the chimeric CLPs-based blocking ELISA displayed the best detection performance, with an AUC of 0.9961, a sensitivity of 97.65%, and a specificity of 95.24% in ROC analysis. Compared with western blot and a commercial c-ELISA for detecting anti-ASFV antibodies, this method had an excellent agreement of 96.35% (kappa value = 0.911) and 97.76% (kappa value = 0.946) with the other tests, respectively. This ELISA also had high repeatability, with CV < 10%, and no cross-reaction with the serum antibodies against other swine viruses or Orbivirus. In brief, this was the first report on developing a blocking ELISA based on virus-like nanoparticles chimerized with an antigenic epitope of ASFV P54 for serological diagnosis of ASFV.
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