Evaluation of glycoprotein E subunit and live attenuated varicella‐zoster virus vaccines formulated with a single‐strand RNA‐based adjuvant

Lee, Su Jeen; Park, Hyo-Jung; Ko, Hae Li; Lee, Jung Eun; Lee, Hyun Joo; Kim, Hun; Nam, Jae‐Hwan

doi:10.1002/iid3.297

Cited by 8 publications

(6 citation statements)

References 45 publications

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“…By the second boost in the two-boost experiment, seven of eight mice vaccinated with 8MTT had mounted an IgG response to TT, while four of eight vaccinated with CITT had mounted an immune response to TT. Thus, 8MTT is a potent vaccine against native TT challenge and could serve as a conjugate vaccine platform to enhance the immune response to polysaccharides and other macromolecular molecules ( 37 – 39 ) in a rapid response to a microbial pathogen.…”

Section: Discussionmentioning

confidence: 99%

A Novel High-Potency Tetanus Vaccine

Przedpelski

Tepp

Pellett

et al. 2020

mBio

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Chemically inactivated tetanus toxoid (CITT) is clinically effective and widely used. However, CITT is a crude nonmalleable vaccine that contains hundreds of Clostridium tetani proteins, and the active component is present in variable and sometimes minor percentages of vaccine mass. Recombinant production of a genetically inactivated tetanus vaccine offers an opportunity to replace and improve the current tetanus vaccine. Previous studies showed the feasibility of engineering full-length tetanus toxin (TT) in Escherichia coli. In the present study, full-length TT was engineered with eight individual amino acid mutations (8MTT) to inactivate catalysis, translocation, and host receptor-binding functions, retaining 99.4% amino acid identity to native tetanus toxin. 8MTT purified as a 150-kDa single-chain protein, which trypsin nicked to a 100-kDa heavy chain and 50-kDa light chain. The 8MTT was not toxic for outbred mice and was >50 million-fold less toxic than native TT. Relative to CITT, 8MTT vaccination elicited a strong immune response and showed good vaccine potency against TT challenge. The strength of the immune response to both vaccines varied among individual outbred mice. These data support 8MTT as a candidate vaccine against tetanus and a malleable candidate conjugate vaccine platform to enhance the immune response to polysaccharides and other macromolecular molecules to facilitate a rapid response to emerging microbial pathogens. IMPORTANCE Chemical inactivation is a clinically effective mechanism to detoxify protein toxins to produce vaccines against microbial infections and to serve as a platform for production of conjugate polysaccharide vaccines. This method is widely used for the production of protein toxin vaccines, including tetanus toxoid. However, chemical modification alters the protein structure with unknown effects on antigenicity. Here, a recombinant full-length tetanus toxin (TT) is engineered with 8 mutations (8MTT) that inactivate three toxin functions: catalysis, translocation, and receptor binding. 8MTT is nontoxic and elicits a potent immune response in outbred mice. 8MTT also represents a malleable platform for the production of conjugate vaccines, which can facilitate a rapid vaccine response against emerging microbial pathogens.

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Section: Discussionmentioning

confidence: 99%

A Novel High-Potency Tetanus Vaccine

Przedpelski

Tepp

Pellett

et al. 2020

mBio

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“…Shingrix (GSK) is a recombinant subunit vaccine comprising a VZV gE expressed in CHO cells and the liposome-based adjuvant AS01 B . Other work has sought to investigate subunit vaccines against HZ using gE proteins generated from CHO or insect cells formulated with novel adjuvants (Cao et al, 2021;Lee et al, 2020;Luan et al, 2022a, Luan et al, 2022bWang et al, 2021;Wui et al, 2019;Wui et al, 2021). Here, we investigated and showed that the gE protein could be solubly expressed and purified from E. coli, and then formulated as a subunit vaccine candidate with an appropriate adjuvant to elicit not only a robust neutralizing titer but also a strong CMI response.…”

Section: Discussionmentioning

confidence: 99%

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

Chen

Sun

Zhang

et al. 2023

Sci. China Life Sci.

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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

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“…The genes encoding the truncated gE (1-545 aa) [17,18], full-length IE63, IE63-2A-gE (2A: GSGATNFSLLKQAGDVEENPGP), and IE63-linker-gE (linker: LQGGGSRGGG) were synthesized commercially by GenScript Biotech Corp. (Nanjing, China) and were inserted into the pcDNA3.1(+) vector for the expression of heterologous proteins in mammalian cells.…”

Section: Dna Plasmidsmentioning

confidence: 99%

“…Therefore, VZV gE is the most commonly chosen antigen for HZ vaccines to induce humoral and cellular immune responses. Previous studies showed an enhanced antibody response when mice were immunized with a truncated form of gE [17,18]. Therefore, we chose the extracellular domain of gE as the antigen in this study.…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity of Varicella Zoster Virus DNA Vaccines Encoding Glycoprotein E and Immediate Early Protein 63 in Mice

Liu

Lin

Cai

et al. 2022

Viruses

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Herpes zoster (HZ) is caused by the reactivation of latent varicella-zoster virus (VZV) from the sensory ganglia due to aging or immunosuppression. Glycoprotein E (gE) is a widely used vaccine antigen for specific humoral and cellular immune responses. Immediate early protein 63 (IE63) is expressed during latency, suggesting that it is a potential antigen against HZ reactivation. In this study, HZ DNA vaccines encoding gE, IE63, IE63-2A-gE (where 2A is a self-cleaving sequence), or IE63-linker-gE were developed and investigated for immunogenicity in mice. The results showed that each HZ DNA vaccine induced VZV-specific antibody production. The neutralizing antibody titer elicited by IE63-2A-gE was comparable to that elicited by gE or live attenuated HZ vaccine (LAV). IE63-2A-gE-induced gE or IE63-specific INF-γ+ T cell frequencies in splenocytes were comparable to those of LAV. Furthermore, IE63-2A-gE, gE, or IE63 led to a significant increase in IFN-γ (IE63 stimulation) and IL-2 (gE stimulation) secretion compared to LAV, showing a Th1-biased immune response. Moreover, IE63-2A-gE and gE induced cytotoxic activity of CD8+ T cells compared to that of LAV. This study elucidates that the IE63-2A-gE DNA vaccine can induce both humoral and cell-mediated immune responses, which provides a candidate for the development of an HZ vaccine.

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Evaluation of glycoprotein E subunit and live attenuated varicella‐zoster virus vaccines formulated with a single‐strand RNA‐based adjuvant

Cited by 8 publications

References 45 publications

A Novel High-Potency Tetanus Vaccine

A Novel High-Potency Tetanus Vaccine

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

Immunogenicity of Varicella Zoster Virus DNA Vaccines Encoding Glycoprotein E and Immediate Early Protein 63 in Mice

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