Truncated glycoprotein E of varicella-zoster virus is an ideal immunogen for Escherichia coli-based vaccine design

Abstract

Varicella-zoster virus (VZV) is a highly infectious agent responsible for both varicella and herpes zoster disease. Despite high efficacy, there remain safety and accessibility concerns with the licensed vaccines. Here, we sought to produce a VZV gE immunogen using an E. coli expression system. We found that the soluble expression and yield of gE protein could be enhanced via C-terminal truncations to the protein, thereby facilitating a robust and scalable purification process for the purpose of vaccine manufacturing. The lead truncated gE (aa 31-358), hereafter referred to as tgE, was a homogenous monomer in solution and showed excellent antigenicity. Finally, we assessed and compared the immunogenicity of tgE with commercial vOka LAV and Shingrix vaccine. We found that aluminum-adjuvanted tgE was immunogenic as compared with vOka LAV. When adjuvanted with AS01 B , a two-dose immunization of tgE showed comparable or better potency in antibody responses and cell-mediated immunity with those of the Shingrix vaccine at the same dosage, especially in terms of the proportion of IFN-γ-expressing CD4 + T cells. In conclusion, this method of E. coli-mediate tgE expression offers a cost-effective and scalable strategy to generate an ideal VZV gE immunogen for the development of both varicella and zoster vaccines. varicella-zoster virus, glycoprotein E, Escherichia coli, vaccine

Herpes zoster mRNA vaccine induces superior vaccine immunity over licensed vaccine in mice and rhesus macaques

“…gE is abundantly present on the surface of viral particle and also on the plasma membrane of VZV-infected cells, which has been reported to mediate viral spread and skin tropism, as well as the formation of infectious virions [1]. Moreover, gE is highly immunogenic in eliciting both antibody and cell-mediated immune (CMI) responses and is believed to be a key immunogen for VZV vaccine development [2][3][4]. A live-attenuated vaccine (Zostavax, Merck) and a protein-based subunit vaccine containing carboxyl-terminal truncated form of gE adjuvanted with AS01B (Shingrix) have been approved in clinical use, of which Shingrix showed a remarkably higher protective efficacy (97.2%) than Zostavax (51.3%) in adults above 50 years of age [5].…”