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Antibody Generation and Immunogenicity Analysis of EBV gp42 N-Terminal Region.

ABSTRACT: Epstein-Barr virus (EBV) is the first reported oncogenic virus and infects more than 90% of adults worldwide. EBV can establish a latent infection in B lymphocytes which is essential for persistence and transmission. Glycoprotein gp42 is an indispensable member of the triggering complex for EBV entry into a B cell. The N-terminal region of gp42 plays a key role in binding to gH/gL and triggering subsequent membrane fusion. However, no antibody has been reported to recognize this region and the immunogenicity of gp42 N-domain remains unknown. In the present study, we have generated a panel of nine mAbs against the gp42 N-terminal region (six mAbs to gp42-44-61aa and three mAbs to gp42-67-81aa). These mAbs show excellent binding activity and recognize different key residues locating on the gp42 N-domain. Among the nine mAbs, 4H7, 4H8 and 11G10 cross-react with rhLCV-gp42 while other mAbs specifically recognize EBV-gp42. Our newly obtained mAbs provide a useful tool for investigating the gp42 function and viral infection mechanism of γ-Herpesvirus. Furthermore, we assess the immunogenicity of the gp42 N-terminal region using the HBc149 particle as a carrier protein. The chimeric VLPs can induce high antibody titers and elicit neutralizing humoral responses to block EBV infection. More rational and effective designs are required to promote the gp42-N terminal region to become an epitope-based vaccine.

SUBMITTER: Hong J

PROVIDER: S-EPMC8707153 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundDespite its semi-commercial status, ethanol production from lignocellulosics presents many complexities not yet fully solved. Since the pretreatment stage has been recognized as a complex and yield-determining step, it has been extensively studied. However, economic success of the production process also requires optimization of the biochemical conversion stage. This work addresses the search of bioreactor configurations with improved residence times for continuous enzymatic saccharification and fermentation operations. Instead of analyzing each possible configuration through simulation, we apply graphical methods to optimize the residence time of reactor networks composed of steady-state reactors. Although this can be easily made for processes described by a single kinetic expression, reactions under analysis do not exhibit this feature. Hence, the attainable region method, able to handle multiple species and its reactions, was applied for continuous reactors. Additionally, the effects of the sugars contained in the pretreatment liquor over the enzymatic hydrolysis and simultaneous saccharification and fermentation (SSF) were assessed.ResultsWe obtained candidate attainable regions for separate enzymatic hydrolysis and fermentation (SHF) and SSF operations, both fed with pretreated corn stover. Results show that, despite the complexity of the reaction networks and underlying kinetics, the reactor networks that minimize the residence time can be constructed by using plug flow reactors and continuous stirred tank reactors. Regarding the effect of soluble solids in the feed stream to the reactor network, for SHF higher glucose concentration and yield are achieved for enzymatic hydrolysis with washed solids. Similarly, for SSF, higher yields and bioethanol titers are obtained using this substrate.ConclusionsIn this work, we demonstrated the capabilities of the attainable region analysis as a tool to assess the optimal reactor network with minimum residence time applied to the SHF and SSF operations for lignocellulosic ethanol production. The methodology can be readily modified to evaluate other kinetic models of different substrates, enzymes and microorganisms when available. From the obtained results, the most suitable reactor configuration considering residence time and rheological aspects is a continuous stirred tank reactor followed by a plug flow reactor (both in SSF mode) using washed solids as substrate.

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Antibody Generation and Immunogenicity Analysis of EBV gp42 N-Terminal Region.

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