Dataset Information

Designed chimeric nanoparticle displaying viral fusion apparatus elicit potent neutralizing antibody against Epstein-Barr virus infection

ABSTRACT: Epstein-Barr virus (EBV) ubiquitously infects global population and leads to a variety malignancies and autoimmune diseases. It establishes its lytic-latency life cycle relying on the tropism transition between B cell and epithelial cell, during which its critical glycoprotein gB and gHgL act as the fusion apparatus mediating viral recognition and membrane fusion in either cell type. Thus. simultaneous targeting to fusion apparatus would be ideal strategy to construct potent EBV prophylactic vaccine. In this study, we designed chimeric nanoparticle multivalently displaying gB and gHgL with even gp42 upon the nanoparticle surface, inducing significantly robust neutralizing antibody generation in both murine and non-human primate models. As we further identify the comparable immunization potency between chimeric nanoparticle and whole live virion and preponderance of gB in neutralizing antibody elicitation, we used single-B cell sequencing to dissect the B cell response to chimeric nanoparticle immunization in mouse and isolate a gB-specific neutralizing antibody Fab5 targeting novel vulnerable site. These findings offers insight to advanced vaccine design for EBV and other herpesviruses.

ORGANISM(S): Mus musculus

PROVIDER: GSE245792 | GEO | 2025/01/01

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Human papilloma (HPV) virus-like particle (VLP) vaccines were recently licensed. Though neutralizing antibody titers are thought to be the main effectors of protection against infection, early predictors of long-term efficacy are not yet defined and a comprehensive understanding of innate and adaptive immune responses to vaccination is still lacking. Here, microarrays were used to compare the gene expression signature in HPV-16 L1 VLP-stimulated PBMC from 17 vaccine and 4 placebo recipients before vaccination, and 1 month after receiving the second immunization. Vaccination with HPV-16 L1 VLP was associated with modulation of genes involved in the inflammatory/defense response, cytokine, interferon and cell cycle pathways in VLP-stimulated PBMC. In addition, there was up-regulation of probesets associated with cytotoxic (GZMB, TNFSF10) and regulatory (INDO, CTLA4) activities. The strongest correlations with neutralizing antibody titers were found for cyclin d2 (CCND2) and galectin (LGALS2). Twenty-two differentially expressed probesets were selected for confirmation by RT-PCR in an independent sample set. Agreement with the microarray data was seen for over two-thirds of these probesets. Up-regulation of immune/defense response genes by VLP, in particular interferon-induced genes was observed in PBMC collected prior to vaccination, with many of these genes being further induced following vaccination. In conclusion, we used gene expression profiling to identify important innate and adaptive response related- genes induced by vaccination with HPV VLP. Further studies are needed to identify gene expression signatures of immunogenicity and long-term protection with potential utility in prediction of long-term HPV vaccination outcomes in clinical trials. Experiment Overall Design: Microarrays (Affymetrix Human Focus) were used to compare the gene expression signature in PBMCs stimulated for 3 days with media alone, Sf9/baculovirus insect cell lysate, and HPV-16 L1 VLP expressed from baculovirus-infected Sf9 insect cells from 17 vaccine and 4 placebo recipients before vaccination, and 1 month after receiving the second immunization (2 months after the initial immunization. Post-vaccination baculovirus sample for Pt078 and pre-vaccination baculovirus sample for Pt082 failed QC.

Dataset Information

Designed chimeric nanoparticle displaying viral fusion apparatus elicit potent neutralizing antibody against Epstein-Barr virus infection

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets