ABSTRACT
Porcine rotavirus (PoRV) poses a threat to the development of animal husbandry and human health, leading to substantial economic losses. VP6 protein is the most abundant component in virus particles and also the core structural protein of the virus. Firstly, this study developed an antibiotic-resistance-free, environmentally friendly expression vector, named asd-araC-PBAD-alr (AAPA). Then Recombinant Lactiplantibacillus plantarum (L. plantarum) strains induced by arabinose to express VP6 and VP6-pFc fusion proteins was constructed. Subsequently, This paper discovered that NC8/Δalr-pCXa-VP6-S and NC8/Δalr-pCXa-VP6-pFc-S could enhance host immunity and prevent rotavirus infection in neonatal mice and piglets. The novel recombinant L. plantarum strains constructed in this study can serve as oral vaccines to boost host immunity, offering a new strategy to prevent PoRV infection.
Subject(s)
Capsid Proteins , Lactobacillus plantarum , Rotavirus Infections , Swine Diseases , Animals , Mice , Animals, Newborn , Antigens, Viral/immunology , Capsid Proteins/immunology , Capsid Proteins/genetics , Lactobacillus plantarum/immunology , Mice, Inbred BALB C , Rotavirus/immunology , Rotavirus Infections/prevention & control , Rotavirus Infections/immunology , Rotavirus Infections/virology , Swine , Swine Diseases/prevention & control , Swine Diseases/virology , Swine Diseases/microbiology , Swine Diseases/immunologyABSTRACT
Influenza A virus (IAV) causes annual epidemics and occasional pandemics, resulting in significant economic losses and numerous fatalities. Current vaccines, typically administered through injection, provide limited protection due to the frequent antigenic shift and drift of IAV strains. Therefore, the development of alternative broad-spectrum vaccine strategies is imperative. Lactic acid bacteria (LAB) represent promising candidates for vaccine engineering due to their low cost, high safety profile, and suitability for oral administration. In this study, we identified a strain of Lactobacillus plantarum (Lp) that is resistant to acid and bile salts and capable of colonizing the intestines of mice. Subsequently, we employed the RecE/T gene editing system to integrate headless hemagglutinins (mini-HA) into the genome of Lp, generating Lp-mini-HA-SP. Remarkably, immunization with Lp-mini-HA-SP elicited serum IgG antibody responses and conferred immune protection against H9N2 and H1N1 influenza virus challenges. Collectively, our findings offer a novel approach for the development of orally administered IAV vaccines and hold significant potential for future drug development endeavors.
Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza A Virus, H9N2 Subtype , Influenza Vaccines , Lactobacillus plantarum , Orthomyxoviridae Infections , Vaccines, Synthetic , Lactobacillus plantarum/genetics , Lactobacillus plantarum/immunology , Animals , Influenza A Virus, H9N2 Subtype/immunology , Influenza A Virus, H9N2 Subtype/genetics , Influenza A Virus, H1N1 Subtype/immunology , Mice , Influenza Vaccines/immunology , Orthomyxoviridae Infections/prevention & control , Orthomyxoviridae Infections/immunology , Vaccines, Synthetic/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Female , Mice, Inbred BALB CABSTRACT
BACKGROUND: Chicken coccidiosis is a protozoan disease that leads to considerable economic losses in the poultry industry. Live oocyst vaccination is currently the most effective measure for the prevention of coccidiosis. However, it provides limited protection with several drawbacks, such as poor immunological protection and potential reversion to virulence. Therefore, the development of effective and safe vaccines against chicken coccidiosis is still urgently needed. METHODS: In this study, a novel oral vaccine against Eimeria tenella was developed by constructing a recombinant Lactobacillus plantarum (NC8) strain expressing the E. tenella RON2 protein. We administered recombinant L. plantarum orally at 3, 4 and 5 days of age and again at 17, 18 and 19 days of age. Meanwhile, each chick in the commercial vaccine group was immunized with 3 × 102 live oocysts of coccidia. A total of 5 × 104 sporulated oocysts of E. tenella were inoculated in each chicken at 30 days. Then, the immunoprotection effect was evaluated after E. tenella infection. RESULTS: The results showed that the proportion of CD4+ and CD8+ T cells, the proliferative ability of spleen lymphocytes, inflammatory cytokine levels and specific antibody titers of chicks immunized with recombinant L. plantarum were significantly increased (P < 0.05). The relative body weight gains were increased and the number of oocysts per gram (OPG) was decreased after E. tenella challenge. Moreover, the lesion scores and histopathological cecum sections showed that recombinant L. plantarum can significantly relieve pathological damage in the cecum. The ACI was 170.89 in the recombinant L. plantarum group, which was higher than the 150.14 in the commercial vaccine group. CONCLUSIONS: These above results indicate that L. plantarum expressing RON2 improved humoral and cellular immunity and enhanced immunoprotection against E. tenella. The protective efficacy was superior to that of vaccination with the commercial live oocyst vaccine. This study suggests that recombinant L. plantarum expressing the RON2 protein provides a promising strategy for vaccine development against coccidiosis.
Subject(s)
Chickens , Coccidiosis , Eimeria tenella , Lactobacillus plantarum , Poultry Diseases , Protozoan Proteins , Protozoan Vaccines , Vaccination , Animals , Eimeria tenella/immunology , Eimeria tenella/genetics , Coccidiosis/prevention & control , Coccidiosis/veterinary , Coccidiosis/immunology , Poultry Diseases/prevention & control , Poultry Diseases/parasitology , Protozoan Vaccines/immunology , Protozoan Vaccines/genetics , Protozoan Vaccines/administration & dosage , Lactobacillus plantarum/genetics , Lactobacillus plantarum/immunology , Administration, Oral , Protozoan Proteins/immunology , Protozoan Proteins/genetics , Vaccination/veterinary , Antibodies, Protozoan/blood , Vaccines, Synthetic/immunology , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/geneticsABSTRACT
GUANKE is a Lactobacillus plantarum isolated from the feces of healthy volunteer. We have previously shown that GUANKE enhances the efficacy of the SARS-CoV-2 vaccine and prolongs the duration of vaccine protection by upregulating the IFN pathway and T and B lymphocyte functions of the host. The purpose of this study was to evaluate the protective effects and mechanism of oral administration of Lactobacillus plantarum GUANKE in the influenza (A virus A/Puerto Rico/8/34) infection mouse model. In our experiment, oral administration of GUANKE significantly decreased viral load and increased tight junction proteins expression in lung tissues of influenza-infected mice. After GUANKE was co-cultured with mBMDCs in vitro, mBMDCs' maturity and antiviral ability were enhanced, and matured mBMDCs induced polarization of naïve CD4+ T cells into T helper (Th) 1 cells. Adoptive transfer of GUANKE-treated mBMDCs could protect mice from influenza infections. This study suggests that oral administration of Lactobacillus plantarum GUANKE could provide protection against influenza infection in mice, and this protective effect may be mediated, at least in part, by dendritic cells.