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A single epitope of Epstein-Barr Virus stimulate IgG production in mice.

ABSTRACT: Background:Epstein-Barr virus (EBV) is closely associated with the high incidence of nasopharyngeal carcinoma in worldwide. Vaccination is one strategy with the potential to prevent the occurrence of EBV-associated cancers, but a suitable vaccine is yet to be licensed. Much vaccine development research focuses on the GP350/220 protein of EBV as it contains an immunogenic epitope at residues 147-165, which efficiently stimulates IgG production in vitro. We examined the ability of this epitope (EBVepitope) to induce IgG production in mice. Methods:The antibody binding pattern of the epitope was analyzed using bioinformatics tools. The IgG production in mice were examined by FACS Calibur™ Flow cytometer. Results:The epitope bound the 72A1 monoclonal antibody at the same site as GP350/220 protein, indicating that the epitope should stimulate B cells to produce antibody. Moreover, in vivo administration of EBVepitope successfully induced IgG expression from B cells, compared with controls. Further investigation indicated that the relative number of B cells expressing IgE in EBVepitope-treated mice was lower than controls. Conclusions:Our data suggest that this EBV GP350 epitope is able to induce IgG expression in vivo without causing allergic reactions, and represents a potential EBV vaccine candidate.

SUBMITTER: Widodo

PROVIDER: S-EPMC6170204 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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A single epitope of Epstein-Barr Virus stimulate IgG production in mice.

Widodo Pristiwanto Bambang B Rifa'i Muhaimin M Mustafa Irfan I Huyop Fahrul Zaman FZ

Annals of medicine and surgery (2012) 20180919

<h4>Background</h4>Epstein-Barr virus (EBV) is closely associated with the high incidence of nasopharyngeal carcinoma in worldwide. Vaccination is one strategy with the potential to prevent the occurrence of EBV-associated cancers, but a suitable vaccine is yet to be licensed. Much vaccine development research focuses on the GP350/220 protein of EBV as it contains an immunogenic epitope at residues 147-165, which efficiently stimulates IgG production <i>in vitro</i>. We examined the ability of t ...[more]

PMID: 30294429

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Project description:Glycoprotein B (gB) is an essential fusion protein for the Epstein-Barr virus (EBV) infection of both B cells and epithelial cells and is thus a promising target antigen for a prophylactic vaccine to prevent or reduce EBV-associated disease. T cell responses play key roles in the control of persistent EBV infection and in the efficacy of a vaccine. However, to date, T cell responses to gB have been characterized for only a limited number of human leukocyte antigen (HLA) alleles. Here, we screened gB T cell epitopes in 23 healthy EBV carriers and ten patients with nasopharyngeal cancer (NPC) using a peptide library spanning the entire gB sequence. We identified twelve novel epitopes in the context of seven new HLA restrictions that are common in Asian populations. Two epitopes, gB214-223 and gB840-849, restricted by HLA-B*58:01 and B*38:02, respectively, elicited specific CD8+ T cell responses to inhibit EBV-driven B cell transformation. Interestingly, gB-specific CD8+ T cells were more frequent in healthy viral carriers with EBV reactivation than in those without EBV reactivation, indicating that EBV reactivation in vivo stimulates both humoral (VCA-gp125-IgA) and cellular responses to gB. We further found that most gB epitopes are conserved among different EBV strains. Our study broadens the diversity and HLA restrictions of gB epitopes and suggests that gB is a common target of T cell responses in healthy viral carriers with EBV reactivation. In particular, the precisely mapped and conserved gB epitopes provide valuable information for prophylactic vaccine development.ImportanceT cells are crucial for the control of persistent EBV infection and the development of EBV-associated diseases. The EBV gB protein is essential for virus entry into B cells and epithelial cells and is thus a target antigen for vaccine development. Understanding T cell responses to gB is important for subunit vaccine design. Herein, we comprehensively characterized T cell responses to full-length gB. Our results expand the available gB epitopes and HLA restrictions, particularly those common in Asian populations. Furthermore, we showed that gB-specific CD8+ T cells inhibit B cell transformation ex vivo and that gB-specific CD8+ T cell responses in vivo may be associated with intermittent EBV reactivation in asymptomatic viral carriers. These gB epitopes are highly conserved among geographically separated EBV strains. Precisely mapped and conserved T cell epitopes may contribute to immune monitoring and to the development of a gB subunit vaccine.

Project description:The main target cells for Epstein-Barr virus (EBV) infection and persistence are B lymphocytes, although T and NK cells can also become infected. In this paper, we characterize the EBV present in 21 pediatric and adult patients who were treated in France for a range of diseases that involve infection of T or NK cells. Of these 21 cases, 5 pediatric patients (21%) and 11 adult patients (52%) were of Caucasian origin. In about 30% of the cases, some of the EBV genomes contain a large deletion. The deletions are different in every patient but tend to cluster near the BART region of the viral genome. Detailed investigation of a family in which several members have persistent T or NK cell infection by EBV indicates that the virus genome deletions arise or are selected independently in each individual patient. Genome sequence polymorphisms in the EBV in these T or NK cell diseases reflect the geographic origin of the patient and not a distinct type of EBV (the 21 cases studied included examples of both type 1 and type 2 EBV infection). Using virus produced from type 1 or type 2 EBV genomes cloned in bacterial artificial chromosome (BAC) vectors, we demonstrate infection of T cells in cord blood from healthy donors. Our results are consistent with transient infection of some T cells being part of normal asymptomatic infection by EBV in young children. IMPORTANCE EBV contributes to several types of human cancer. Some cancers and nonmalignant lymphoproliferative diseases involving T or NK cells contain EBV. These diseases are relatively frequent in Japan and China and have been shown sometimes to have deletions in the EBV genome in the disease cells. We identify further examples of deletions within the EBV genome associated with T or NK cell diseases, and we provide evidence that the virus genomes with these deletions are most likely selected in the individual cases, rather than being transmitted between people during infection. We demonstrate EBV infection of cord blood T cells by highly characterized, cloned EBV genomes and suggest that transient infection of T cells may be part of normal asymptomatic infection by EBV in young children.

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A single epitope of Epstein-Barr Virus stimulate IgG production in mice.

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A single epitope of Epstein-Barr Virus stimulate IgG production in mice.

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