Intranasal immunization with CpG-B Oligodeoxynucleotides protects CBA mice from lethal equine herpesvirus 1 challenge
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PROVIDER: PRJNA523387 | ENA |
REPOSITORIES: ENA
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Project description:Equine herpesvirus 1 (EHV-1) is the causative agent of a number of equine pathological states, including severe disease of the central nervous system, respiratory infections, and abortion storms. Our results showed that intranasal immunization with CpG-B oligodeoxynucleotides (ODN) protects CBA mice from lethal EHV-1 challenge. IFN-γ and seven interferon-stimulated genes (ISGs) were upregulated 39.4- to 260.3-fold at 8 h postchallenge in the lungs of RacL11-challenged mice that had been immunized with CpG-B ODN. Treatment with 20 ng/ml of IFN-γ reduced EHV-1 yield by 100-fold in MH-S at 4 days post-VZV infection compared to that of untreated cells. However, IFN-γ reduced virus yield by only 2-fold in and mouse fibroblast L-M cells. To identify IFN-γ-stimulated genes that inhibit EHV-1 replication, Affymetrix microarray analyses were performed with IFN-γ-treated MH-S and L-M cells. In MH-S cells, IFN-γ upregulated 551 genes and down-regulated 136 genes as compared to those of untreated cells. In L-M cells, IFN-γ upregulated 225 genes and downregulated 2 genes. Nine genes associated with innate immune response were significantly upregulated only in MH-S cells. Five antiviral ISGs MX1, SAMHD1, NAMPT, TREX1, and DDX60 were upregulated 3.2- to 18.1-fold only in MH-S cells. These results suggest that CpG-B ODN may be used as a prophylactic agent in horses.
2019-02-21 | GSE126813 | GEO
Project description:Equine herpesvirus 1 (EHV-1) is a major pathogen affecting equines worldwide and causes respiratory disease, abortion, and in some cases, neurological disease. EHV-1 strain KyA is attenuated in the mouse and equine, whereas wild-type strain RacL11 induces severe inflammatory infiltration of the lung, causing infected mice to succumb at 4 to 6 days post-infection. Our previous results showed that EHV-1 KyA immunization protected CBA mice from pathogenic RacL11 challenge at 2 and 4 weeks post-immunization, and that the infection with the attenuated KyA elicits protective humoral and cell-mediated immune responses. To investigate the protective mechanisms of EHV-1 KyA by innate immune responses, CBA mice immunized with live KyA were challenged with RacL11 at various times post-vaccination. KyA immunization effectively protected CBA mice from RacL11 challenge at 1 to 7 days post-immunization. Immunized mice lost less than 10% of their preinfection body weight and rapidly regained body weight. Lung virus titers in EHV-1 KyA-immunized CBA mice were 1,000-fold lower at 2 days post-RacL11 challenge than lungs of non-immunized mice, which was indicative of accelerated virus clearance. Affymetrix microarray analysis revealed that IFN-γ and 16 antiviral interferon-stimulated genes (ISGs) were upregulated 3.1- to 48.2-fold at 8 h post-challenge in the lungs of RacL11-challenged mice that had been immunized with KyA. Murine IFN-γinhibited EHV-1 infection of murine alveolar macrophage MH-S cells and effectively protected mice against lethal EHV-1 challenge, suggesting that IFN-γ expression may be important in mediating protection elicited by KyA immunization. These results suggest that EHV-1 KyA can be used as a live attenuated EHV-1 vaccine as well as a prophylactic agent in horses.
2016-05-07 | GSE81219 | GEO
Project description:Intranasal (IN) immunization induces different genotype expression in CD8 memory T cells compared to the CD8 memory T cells induced by intramuscular (IM) immunization. We used microarrays to detail the global program of gene expression underlying the differential induction after IN or IM immunization.
2017-01-28 | GSE77366 | GEO
Project description:UnlabelledEquine herpesvirus 1 (EHV-1) is a major pathogen affecting equines worldwide. The virus causes respiratory disease, abortion, and, in some cases, neurological disease. EHV-1 strain KyA is attenuated in the mouse and equine, whereas wild-type strain RacL11 induces severe inflammation of the lung, causing infected mice to succumb at 4 to 6 days postinfection. Our previous results showed that KyA immunization protected CBA mice from pathogenic RacL11 challenge at 2 and 4 weeks postimmunization and that KyA infection elicited protective humoral and cell-mediated immune responses. To investigate the protective mechanisms of innate immune responses to KyA, KyA-immunized mice were challenged with RacL11 at various times postvaccination. KyA immunization protected mice from RacL11 challenge at 1 to 7 days postimmunization. Immunized mice lost less than 10% of their body weight and rapidly regained weight. Virus titers in the lungs of KyA-immunized mice were 1,000-fold lower at 2 days post-RacL11 challenge than virus titers in the lungs of nonimmunized mice, indicating accelerated virus clearance. Affymetrix microarray analysis revealed that gamma interferon (IFN-γ) and 16 antiviral interferon-stimulated genes (ISGs) were upregulated 3.1- to 48.2-fold at 8 h postchallenge in the lungs of RacL11-challenged mice that had been immunized with KyA. Murine IFN-γ inhibited EHV-1 infection of murine alveolar macrophages and protected mice against lethal EHV-1 challenge, suggesting that IFN-γ expression is important in mediating the protection elicited by KyA immunization. These results suggest that EHV-1 KyA may be used as a live attenuated EHV-1 vaccine as well as a prophylactic agent in horses.ImportanceViral infection of cells initiates a signal cascade of events that ultimately attempts to limit viral replication and prevent infection through the expression of host antiviral proteins. In this study, we show that EHV-1 KyA immunization effectively protected CBA mice from pathogenic RacL11 challenge at 1 to 7 days postvaccination and increased the expression of IFN-γ and 16 antiviral interferon-stimulated genes (ISGs). The administration of IFN-γ blocked EHV-1 replication in murine alveolar macrophages and mouse lungs and protected mice from lethal challenge. To our knowledge, this is the first report of an attenuated EHV-1 vaccine that protects the animal at 1 to 7 days postimmunization by innate immune responses. Our findings suggested that IFN-γ serves as a novel prophylactic agent and may offer new strategies for the development of anti-EHV-1 agents in the equine.
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Project description:To investigate pre-existing mucosal immunity in equine herpesvirus type 1 (EHV-1) immune and non-immune horses during experimental viral challenge. RNAseq was performed on nasal mucosal swab samples from immune and non-immune horses from pre (d-2), early (d1pi and d3pi), mid (d8pi and d10pi), and late (d18pi) infection.
2024-05-08 | GSE232941 | GEO
Project description:Brucellosis is a serious zoonotic disease caused by the genus Brucella, a group of Gram-negative and facultative intracellular bacteria. At present, although live attenuated vaccine such as Rev.1, S19 and RB51 have been widely used for bovine brucellosis, these vaccines have some drawbacks, and safe and effective alternatives have been demanded. Previously, our group showed that several Brucella proteins malate dehydrogenase (rMDH) are effective in eliciting IgG responses in murine model following intraperitoneal injection. The Brucella infections are usually transmitted through mucosal membrane via oral or aerosol exposure. Therefore, induction of mucosal immunity is promising contribute in development of vaccine. In the study, rMDH was loaded with chitosan nanoparticles (CNs) which is mucoadhesive, biocompatible, nontoxic, and immune-enhancing adjuvant to induce both systemic and mucosal immunity. Then, in order to evaluate immunogenicity of the antigen in BALB/C mouse, total RNA from nasal-associated lymphoid tissues at 1 h, 6 h, 12 h after intranasal immunization was analyzed using RNA-seq.
2019-01-29 | GSE125765 | GEO
Project description:The development of a prophylactic vaccine for Kaposi sarcoma-associated Herpesvirus (KSHV) would prevent consequences from infection including disorders such as Kaposi sarcoma and primary effusion lymphoma. Here, we study the immunogenicity of noninfectious virus-like vesicles (VLVs) of KSHV as a potential future vaccine platform. VLVs present a repertoire of viral structural proteins but are noninfectious due to a defect in capsid formation that prevents viral DNA packaging. Immunization of mice with adjuvanted VLVs results in virus-specific antibodies and T cells. These antibodies neutralize viral infection, and this neutralization is enhanced by the complement system. Complement-enhanced neutralization is dependent on antibodies targeting the SCR region of viral ORF4. However, this activity was not present in serum from KSHV-infected humans. Our study highlights an important role of antibody effector functions in the development of a future KSHV vaccine
2023-02-01 | PXD035478 | Pride
Project description:RNA-sequencing of NALT from mouse after intranasal immunization with B. abortus rMDH loaded chitosan nanoparticles (CNs)
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Project description:Mucosal immune response against equine herpesvirus type 1
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Project description:Differing from other experimental models, intranasal infection with vaccine strain of Venezuelan equine encephalitis virus, VEEV, (TC83) caused high titer infection in the brain and 90–100% mortality in the C3H/HeN murine model. Intranasal infection with VEEV (TC83) caused persistent viral infection in the brains of mice without functional αβ T-cells (αβ-TCR -/-). While wild-type C57BL/6 mice clear infectious virus in the brain by 13 dpi, αβ-TCR -/- maintain infectious virus in the brain to 92 dpi. To better characterize the susceptibility to disease development in different strains of mice, we have analyzed the gene transcriptomes in the brains of infected mice.
2016-12-10 | GSE91074 | GEO