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Master Thesis

Principales cibles d’intérêt pour le développement d’un vaccin prophylactique ou thérapeutique contre le virus d’Epstein-Barr : focus sur la glycoprotéine gB

Abstract : Symptomatic primary infection with the Epstein-Barr virus (EBV) corresponds to infectious mononucleosis and 1.5% of cancers worldwide are attributable to the persistence of this virus. However, no effective treatment or vaccine against EBV is currently available. Knowledge of the proteins and mechanisms involved in the different stages of the viral cycle is essential for the development of effective vaccines. This work describes the main proteins involved in the entry of the virus into B cells and epithelial cells that are targets of interest for the development of prophylactic vaccines to prevent viral infection. It also summarizes the role of different proteins involved in the latency and lytic cycle of EBV, that are targets of interest for the development of therapeutic vaccines aimed at stimulating T cell immunity against EBV-associated cancers. Our experimental study focused on the gB glycoprotein, a fusion protein which is essential for the entry of the virus into cells. In order to explore antibody responses against gB in its pre-fusion form (target of neutralization), we constructed gB mutants, described by Garcia et al. as being better expressed on the cell surface than wild type gB (gBWT). Using the murine anti-gB antibody 5B2 (and EBV seropositive human sera) in cell immunofluorescence experiments, we showed that the gB781 mutant was more highly expressed than gBWT and other gB mutants, as shown by Garcia et al. with another commercial murine anti-gB antibody (CL55). Furthermore, our results confirm the presence of anti-gB antibodies in sera of EBV + patients and in human polyvalent immunoglobulin medicines. Also, we have shown that the higher the anti-VCA IgG level (measured with routine serological tests) or the higher the anti-gB IgG level (measured experimentally with the gB825 construct), the higher the neutralizing antibody titer (assessed by the 50% inhibitory dilution: ID50). These preliminary results suggest that the anti-gB antibodies present in the selected sera may be partly responsible for the neutralizing activity. The gB expression system that we have developed, together with EBV infection seroneutralization assays, may help us to analyze antibody responses of patients with EBV-associated diseases and to isolate monoclonal antibodies against this protein.
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Master Thesis
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https://dumas.ccsd.cnrs.fr/dumas-03423475
Contributor : Jean-Hugues Morneau Connect in order to contact the contributor
Submitted on : Wednesday, November 10, 2021 - 10:09:09 AM
Last modification on : Friday, November 12, 2021 - 3:31:11 AM

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  • HAL Id : dumas-03423475, version 1

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Vincent Jean-Pierre. Principales cibles d’intérêt pour le développement d’un vaccin prophylactique ou thérapeutique contre le virus d’Epstein-Barr : focus sur la glycoprotéine gB. Sciences pharmaceutiques. 2021. ⟨dumas-03423475⟩

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