Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ANTI-CD40 DENDRITIC CELL-TARGETING VACCINE INDUCES PROTECTIVE IMMUNITY AGAINST NIPAH DISEASE

ABSTRACT: Nipah virus (NiV) is an emerging paramyxovirus which causes severe respiratory illness and deathly encephalitis in humans.Improving the ability of vaccines to induce strong, cellular, and humoral immune responses, remains the challenge to respond to Nipah and future Henipavirus infections rapidly and efficiently. A CD40.NiV vaccine has been engineered by fusing to the anti-CD40 monoclonal Ab the ectodomain of the Nipah G protein (Bangladesh strain) and immunogenic and conserved NiV F and N peptides. In mice, CD40.NiV promotes poly-antigenic T cell responses and significantly improves anti-NiV G IgG responses compared to the non-targeted NiV G immunogenic protein, in terms of avidity and neutralization potency. Immunogenicity was confirmed in the AGM (African Green Monkey) model, with induction of cross-neutralizing sera against circulating NiV strains and Hendra virus (HeV). Challenge experiment using NiV-B strain demonstrated the high protective efficacy of the vaccine with 100% survival in vaccinated group as compared to 100% lethality in controls. Surviving animals did not exhibit NiV viral replication in the blood, organs and swabs suggesting a sterilizing immunity conferred by the CD40.NiV vaccine. Taken together, results obtained with CD40.NiV vaccine are highly promising in terms of breadth and viral efficacy against NiV.

ORGANISM(S): Chlorocebus sabaeus

PROVIDER: GSE245374 | GEO | 2024/02/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Analysis of the early transcriptome signature of infection of primary endothelial cells by Nipah virus vs. Nipah virus deleted for the expression of non-structural C protein

2012-10-01 | GSE33133 | GEO

Analysis of the early transcriptome signature of Nipah virus infection in primary endothelial cells

Project description:Nipah virus (NiV) is a recently emerged zoonotic Paramyxovirus that causes regular outbreaks in East Asia with mortality rate exceeding 75%. Major cellular targets of NiV infection are endothelial cells and neurons. To better understand virus-host interaction, we analysed the transcriptome profile of NiV infection in primary human umbilical vein endothelial cells. We found that NiV infection strongly induces genes involved in interferon response in endothelial cells. Among the top ten upregulated genes, we identified the chemokine CXCL10 (interferon-induced protein 10, IP-10), an important chemoattractant involved in the generation of inflammatory immune response and neurotoxicity. We performed microarray gene expression profiling of NiV infected HUVEC cell (2 replicates) and of uninfected HUVEC cell (2 replicates).

2012-08-24 | E-GEOD-32902 | biostudies-arrayexpress

Analysis of the early transcriptome signature of infection of primary endothelial cells by Nipah virus vs. Nipah virus deleted for the expression of non-structural C protein

Project description:Nipah virus (NiV) is a highly pathogenic, negative strand RNA paramyxovirus that has recently emerged from flying foxes to cause serious human disease. To study the poorly-understood role of nonstructural NiV proteins in NiV pathogenesis, we generated recombinant viruse lacking the expression of accesory NiV C protein (NiVM-bM-^HM-^FC). To analyse the molecular basis of NiVM-bM-^HM-^FC attenuation we have used the gene microarray approach to study early changes of gene expression in infected primary human endothelial cells, which is a major cellular target of human NiV infection. We performed microarray gene expression profiling of NiV infected HUVEC cell (2 replicates), of uninfected HUVEC cell (2 replicates) and of NiVM-bM-^HM-^FC infected HUVEC cell (2 replicates).

2012-10-01 | E-GEOD-33133 | biostudies-arrayexpress

Analysis of the early transcriptome signature of Nipah virus infection in primary endothelial cells

2012-08-24 | GSE32902 | GEO

Analysis of Nipah virus replication and host proteome response patterns in differentiated porcine airway epithelial cells cultured at the air-liquid interface

Project description:Respiratory tract epithelium infection is considered crucial for airborne transmission of Nipah virus (NiV). Knowledge about infection dynamics and host responses to NiV infection in respiratory tract epithelia is scarce. Various studies in non-differentiated primary respiratory tract cells or cell lines indicate limitations in interferon responses. However, comprehensive studies determining complex reaction patterns in differentiated respiratory tract epithelia to understand efficient NiV replication and spread in swine populations are lacking. Here we characterized infection and spread of NiV in differentiated primary porcine bronchial epithelial cells (PBEC) cultivated at the air-liquid-interface (ALI). After initial infection of only a few apical cells, lateral spread for 12 days with disruption of the epithelium was observed without releasing substantial amounts of infectious virus from the apical or basal sides. Deep time course proteomics revealed pronounced upregulation of genes related to type I/II interferon (IFN), immunoproteasomal subunits, TAP-mediated peptide transport and MHC I antigen presentation, whereas spliceosomal factors were downregulated. We deduce a model in which NiV replication in pig bronchial epithelia is slowed by a potent and broad type I/II interferon host response with concurrent conversion from 26S proteasomal to immunoproteasomal antigen processing and improved MHC I presentation as a crucial step in adaptive immunity priming. Moreover, strong cytopathic effects observed in infected areas could reflect focal release of cell-associated NiV. Cell-associated NiV may translate into the source of efficient airborne viral spread in vivo with a high local infectious dose leading to high and fast spread of NiV throughout pig herds.

2023-05-10 | PXD032673 | Pride

Structure and antigenicity of divergent Henipavirus fusion glycoproteins

Project description:A novel henipavirus (HNV) named Langya virus (LayV) was isolated in human patients in China in August 2022. It is closely related to Mòjiāng virus (MojV) and represents the first instance of HNV zoonosis to humans outside of Nipah virus (NiV) and Hendra viruses (HeV). Within this work, mass spectrometry glycoproteomic analysis revealed that although the LayV F protein has reduced glycosylation compared to its NiV and HeV counterparts, a unique glycan was identified positioned at the DIII apex, shielding a previously identified site of vulnerability in NiV F.

2023-05-03 | PXD039898 | Pride

Gene expression profiling of rhesus macaques vaccinated with ALVAC-SIVgpe DNA + SIVgp120 protein subunit and unvaccinated controls after challenge with SIVmac251 - 3 wks post-infection

Project description:The SIVmac251 macaque model has been used to evaluate the efficacy of vaccine for HIV. Exposure of macaques to a single high dose of SIVmac251 results in transmission of multiple viral variants, which contrasts the few HIV variants typically transmitted in humans. In here, we investigated whether the dose of SIVmac251 challenge affected vaccination efficacy and found that exposure of the immunized macaques to single high dose of SIVmac251 resulted in no vaccine efficacy, whereas exposure to a tenfold lower dose resulted in protection from SIVmac251 acquisition and protection from disease in animals that become infected. The dose of challenge did not affect the expression of inflammatory genes in the gut in acute infection, but at set point, a significant down regulation of interferon responsive genes and up regulation of genes involved in B and T-cell responses, was observed only in vaccinated animals exposed to a lower dose of SIVmac251. Accordingly, in these animals, we also found a significant correlation with vaccine induced T-cell responses and protection from disease. These data demonstrate that the evaluation of the efficacy of vaccine candidates for HIV relies on accurate modeling in macaques to better mimic HIV transmission to humans. A total of 31 RNA samples were hybridized on to Rhesus Affymetrix 3' Expression arrays. The study was composed of 8 vaccinated and 10 control animals subjected to a low dose challenge and 6 vaccinated and 7 control animals subjected to a high dose challenge

2013-03-01 | E-GEOD-37311 | biostudies-arrayexpress

Gene expression profiling of rhesus macaques vaccinated with ALVAC-SIVgpe DNA + SIVgp120 protein subunit and unvaccinated controls after challenge with SIVmac251 - 11 wks post-infection

Project description:The SIVmac251 macaque model has been used to evaluate the efficacy of vaccine for HIV. Exposure of macaques to a single high dose of SIVmac251 results in transmission of multiple viral variants, which contrasts the few HIV variants typically transmitted in humans. In here, we investigated whether the dose of SIVmac251 challenge affected vaccination efficacy and found that exposure of the immunized macaques to single high dose of SIVmac251 resulted in no vaccine efficacy, whereas exposure to a tenfold lower dose resulted in protection from SIVmac251 acquisition and protection from disease in animals that become infected. The dose of challenge did not affect the expression of inflammatory genes in the gut in acute infection, but at set point, a significant down regulation of interferon responsive genes and up regulation of genes involved in B and T-cell responses, was observed only in vaccinated animals exposed to a lower dose of SIVmac251. Accordingly, in these animals, we also found a significant correlation with vaccine induced T-cell responses and protection from disease. These data demonstrate that the evaluation of the efficacy of vaccine candidates for HIV relies on accurate modeling in macaques to better mimic HIV transmission to humans. A total of 34 RNA samples were hybridized on to Rhesus Affymetrix 3' Expression arrays. The study was composed of 9 vaccinated and 9 control animals subjected to a low dose challenge and 7 vaccinated and 9 control animals subjected to a high dose challenge

2013-03-01 | E-GEOD-37312 | biostudies-arrayexpress

Candidate Vaccine Assessment in a pH1N1 Rhesus Macaque Challenge Model

Project description:A mixed-aerosol pH1N1 (Cal04) challenge of rhesus macaques was establised to serve as a pre-clinical model for the evaluation of candidate vaccines. After characterizing the clinical signs and immune responses associated with pH1N1 challenge in naïve rhesus macaques, a follow-up study assessing 2 candidate vaccines was performed. This study has 2 phases: 1) Model Establisment consisting of 3 groups: Unvaccinated Live Challenge (n=3, Unvaccinated UV-inactivated Challenge (n=3), Previously Vaccinated Live Challenge (n=3) which were sampled at 2 baseline timepoints Day -7 and Day 0. Following the H1N1 Challenge, samples were collected at day 1,2,5,8,14,20. 2) Candidate Vaccine Assessment consisting of four groups: Previously Vaccinted with anti-CD40-NP5+PolyICLC (n=4), Previously vaccinated with CD40-HA+PolyICLC (n=4), Previously vaccinated with commercial mismatched Fluzone (n=4), Previously vaccinated with Media+PolyICLC alone (n=4). Daseline samples were collected at Day -7 and 0 (baseline) and Day 1,3,6,14,20 post-challenge.

2014-10-24 | E-GEOD-60009 | biostudies-arrayexpress