Mucosal immune responses induced by oral administration recombinant Bacillus subtilis expressing the COE antigen of PEDV in newborn piglets

Abstract Porcine epidemic diarrhea (PED) is a highly contagious disease in newborn piglets and causes substantial economic losses in the world. PED virus (PEDV) spreads by fecal–oral contact and can be prevented by oral immunization. Therefore, it is necessary to develop an effective oral vaccine against PEDV infection. Currently, Bacillus subtilis as recombinant vaccine carrier has been used for antigen delivery and proved well in immune effect and safety. The present study evaluated the immunogenicity of recombinant Bacillus subtilis (B. subtilis-RC) in piglets via oral administration. After oral immunization in piglets, B. subtilis-RC significantly increased the local mucosal immune responses. Oral administration with B. subtilis-RC significantly improved the level of specific mucosal immunoglobulin A (IgA) antibodies against PEDV infection, through enlarging the area of Peyer’s patches (PPs) and increasing the number of ileum IgA+ secreting (SIgA) cells. In the meantime, B. subtilis-RC remarkably increased the number of intraepithelial lymphocytes (IELs). We also observed that oral administration of B. subtilis-RC significantly increased CD3+T lymphocytes’ numbers and up-regulated the ratio of CD4+/CD8+ T cells. Furthermore, high titers of specific serum immunoglobulin G (IgG) revealed satisfactory systemic immune response against PEDV infection. In summary, our study demonstrated that oral administration of B. subtilis-RC could trigger a high level of local and systemic immune responses and would be a promising candidate vaccine against PEDV infection in piglets.

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Immune Responses in Pregnant Sows Induced by Recombinant Lactobacillus johnsonii Expressing the COE Protein of Porcine Epidemic Diarrhea Virus Provide Protection for Piglets against PEDV Infection

Viruses ◽

10.3390/v14010007 ◽

2021 ◽

Vol 14 (1) ◽

pp. 7

Author(s):

Dianzhong Zheng ◽

Xiaona Wang ◽

Ning Ju ◽

Zhaorui Wang ◽

Ling Sui ◽

...

Keyword(s):

Dendritic Cell ◽

Immune Responses ◽

Porcine Epidemic Diarrhea Virus ◽

Oral Vaccine ◽

Economic Losses ◽

Antigen Delivery ◽

Lactobacillus Johnsonii ◽

Diarrhea Virus ◽

Porcine Epidemic Diarrhea

Porcine epidemic diarrhea (PED) induced by porcine epidemic diarrhea virus (PEDV) is an intestinal infectious disease in pigs that causes serious economic losses to the pig industry. To develop an effective oral vaccine against PEDV infection, we used a swine-origin Lactobacillus johnsonii (L. johnsonii) as an antigen delivery carrier. A recombinant strain pPG-T7g10-COE/L. johnsonii (L. johnsonii-COE) expressing COE protein (a neutralizing epitope of the viral spike protein) was generated. The immunomodulatory effect on dendritic cell in vitro and immunogenicity in pregnant sows was evaluated following oral administration. L. johnsonii-COE could activate monocyte-derived dendritic cell (MoDC) maturation and triggered cell immune responses. After oral vaccination with L. johnsonii-COE, levels of anti-PEDV-specific serum IgG, IgA, and IgM antibodies as well as mucosal secretory immunoglobulin A (SIgA) antibody were induced in pregnant sows. High levels of PEDV-specific SIgA and IgG antibodies were detected in the maternal milk, which provide effective protection for the piglets against PEDV infection. In summary, oral L. johnsonii-COE was able to efficiently activate anti-PEDV humoral and cellular immune responses, demonstrating potential as a vaccine for use in sows to provide protection of their piglets against PEDV.

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Mucosal and systemic immune responses induced by intranasal immunization of recombinant Bacillus subtilis expressing the P97R1, P46 antigens of Mycoplasma hyopneumoniae

Bioscience Reports ◽

10.1042/bsr20191126 ◽

2019 ◽

Vol 39 (10) ◽

Author(s):

Yongheng Wang ◽

Jialu Wang ◽

Mengyun Zhou ◽

Peng Liu ◽

En Zhang ◽

...

Keyword(s):

Bacillus Subtilis ◽

Immune Responses ◽

Mucosal Immunity ◽

Immunoglobulin A ◽

Mycoplasma Hyopneumoniae ◽

Chronic Respiratory Disease ◽

Mucosal Cell ◽

Antigen Delivery ◽

Novel Strategy ◽

Recombinant Bacillus Subtilis

Abstract Mycoplasma hyopneumoniae (M. hyopneumoniae) is the pathogen of swine enzootic pneumonia, a chronic respiratory disease affecting pigs of all ages. The ciliated epithelial cells of the respiratory tract are the main target invaded and colonized by M. hyopneumoniae. Therefore, the ideal vaccine would be mucosally administered and able to stimulate suitable mucosal immunity and prevent the adherence of pathogens to mucosal cell surfaces. Currently, Bacillus subtilis as a recombinant vaccine carrier has been used for antigen delivery and proved to be effectively enhancing the innate immunity of nasal mucosa. Here, our study attempts to construct recombinant Bacillus subtilis (B.S-P97R1, B.S-P46), which can express the P97R1 or P46 antigen of M. hyopneumoniae, and to evaluate the immune responses in BALB/c mice. Initially, we respectively successfully constructed recombinant B.S-P97R1, B.S-P46 and validated the expression of antigen proteins by Western analysis. Then, recombinant B.S-P97R1 or B.S-P46 were respectively intranasally (i.n.) immunized in mice. Both strong P97R1-specific and P46-specific immunoglobulin G (IgG), secretory immunoglobulin A (SIgA) antibodies were induced in sera, bronchoalveolar lavage fluids (BALs) by ELISA analysis. Moreover, the levels of specific IL-4, IFN-γ in the immunized mice were elevated, and the proliferation of lymphocytes was also enhanced. In general, intranasal inoculation of recombinant B.S-P97R1 or B.S-P46 resulted in strong mucosal immunity, cell-mediated and humoral immunity, which was a mixed Th1/Th2-type response. In addition, our results provided a potential novel strategy that may be applied to the development of vaccines against M. hyopneumoniae.

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Intranasal administration with recombinant Bacillus subtilis induces strong mucosal immune responses against pseudorabies

Microbial Cell Factories ◽

10.1186/s12934-019-1151-8 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 5

Author(s):

Jialu Wang ◽

Yongheng Wang ◽

En Zhang ◽

Mengyun Zhou ◽

Jian Lin ◽

...

Keyword(s):

Bacillus Subtilis ◽

Immune Responses ◽

Intranasal Administration ◽

Mucosal Immune Responses ◽

Recombinant Bacillus Subtilis

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Immune responses to the oral administration of recombinant Bacillus subtilis expressing multi-epitopes of foot-and-mouth disease virus and a cholera toxin B subunit

Journal of Virological Methods ◽

10.1016/j.jviromet.2010.11.023 ◽

2011 ◽

Vol 171 (1) ◽

pp. 272-279 ◽

Cited By ~ 7

Author(s):

Bo Hu ◽

Chang Li ◽

Huijun Lu ◽

Zhanbo Zhu ◽

Shouwen Du ◽

...

Keyword(s):

Bacillus Subtilis ◽

Immune Responses ◽

Oral Administration ◽

Foot And Mouth Disease ◽

Cholera Toxin B Subunit ◽

Toxin B ◽

Cholera Toxin B ◽

B Subunit ◽

Mouth Disease Virus ◽

Recombinant Bacillus Subtilis

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Polyacrylate–Peptide Antigen Conjugate as a Single-Dose Oral Vaccine against Group A Streptococcus

Vaccines ◽

10.3390/vaccines8010023 ◽

2020 ◽

Vol 8 (1) ◽

pp. 23 ◽

Cited By ~ 4

Author(s):

Mohammad Omer Faruck ◽

Lili Zhao ◽

Waleed M. Hussein ◽

Zeinab G. Khalil ◽

Robert J. Capon ◽

...

Keyword(s):

Immune Responses ◽

Group A Streptococcus ◽

Bacterial Colonization ◽

Oral Vaccine ◽

Cell Epitope ◽

Recurrent Infection ◽

Oral Immunization ◽

Medical Intervention ◽

Group A ◽

Mucosal Immune Responses

Group A Streptococcus (GAS)-associated rheumatic heart disease is a leading cause of death caused by GAS infection. While antibiotics can treat the infection in most cases, growing antibiotic resistance, late medical intervention, and recurrent infection are major obstacles to the effective treatment of GAS-associated diseases. As GAS infection typically originates from the bacterial colonization of mucosal tissue in the throat, an oral vaccine that can generate both systemic and mucosal immune responses would solve problems associated with traditional medical interventions. Moreover, orally delivered vaccines are more easily administered and less expensive for mass immunization. In this study, the B-cell epitope J8, derived from GAS M protein, and universal T-helper Pan HLA-DR-binding epitope peptide (PADRE), were conjugated to poly (methyl acrylate) (PMA) to form a self-assembled nanoparticle vaccine candidate (PMA-P-J8). Strong systemic and mucosal immune responses were induced upon single oral immunization of mice with the conjugate. The antibodies generated were opsonic against GAS clinical isolates as measured after boost immunization. Thus, we developed a simple conjugate as an effective, adjuvant-free oral peptide-based vaccine.

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Size effect on systemic and mucosal immune responses induced by oral administration of biodegradable microspheres

Vaccine ◽

10.1016/s0264-410x(96)00149-1 ◽

1996 ◽

Vol 14 (17-18) ◽

pp. 1677-1685 ◽

Cited By ~ 114

Author(s):

Y TABATA

Keyword(s):

Immune Responses ◽

Oral Administration ◽

Size Effect ◽

Biodegradable Microspheres ◽

Mucosal Immune Responses

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Immunogenicity in Swine of Orally Administered Recombinant Lactobacillus plantarum Expressing Classical Swine Fever Virus E2 Protein in Conjunction with Thymosin α-1 as an Adjuvant

Applied and Environmental Microbiology ◽

10.1128/aem.00127-15 ◽

2015 ◽

Vol 81 (11) ◽

pp. 3745-3752 ◽

Cited By ~ 27

Author(s):

Yi-Gang Xu ◽

Xue-Ting Guan ◽

Zhong-Mei Liu ◽

Chang-Yong Tian ◽

Li-Chun Cui

Keyword(s):

Immune Responses ◽

Lactobacillus Plantarum ◽

Classical Swine Fever Virus ◽

Oral Vaccine ◽

Classical Swine Fever ◽

Fever Virus ◽

Economic Losses ◽

E2 Protein ◽

Content Type ◽

Cellular Immune

ABSTRACTClassical swine fever, caused by classical swine fever virus (CSFV), is a highly contagious disease that results in enormous economic losses in pig industries. The E2 protein is one of the main structural proteins of CSFV and is capable of inducing CSFV-neutralizing antibodies and cytotoxic T lymphocyte (CTL) activitiesin vivo. Thymosin α-1 (Tα1), an immune-modifier peptide, plays a very important role in the cellular immune response. In this study, genetically engineeredLactobacillus plantarumbacteria expressing CSFV E2 protein alone (L. plantarum/pYG-E2) and in combination with Tα1 (L. plantarum/pYG-E2-Tα1) were developed, and the immunogenicity of each as an oral vaccine to induce protective immunity against CSFV in pigs was evaluated. The results showed that recombinantL. plantarum/pYG-E2 andL. plantarum/pYG-E2-Tα1 were both able to effectively induce protective immune responses in pigs against CSFV infection by eliciting immunoglobulin A (IgA)-based mucosal, immunoglobulin G (IgG)-based humoral, and CTL-based cellular immune responses via oral vaccination. Significant differences (P< 0.05) in the levels of immune responses were observed betweenL. plantarum/pYG-E2-Tα1 andL. plantarum/pYG-E2, suggesting a better immunogenicity ofL. plantarum/pYG-E2-Tα1 as a result of the Tα1 molecular adjuvant that can enhance immune responsiveness and augment specific lymphocyte functions. Our data suggest that the recombinantLactobacillusmicroecological agent expressing CSFV E2 protein combined with Tα1 as an adjuvant provides a promising strategy for vaccine development against CSFV.

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