Ionizable Lipid Nanoparticles Enhanced the Synergistic Adjuvant Effect of CpG ODNs and QS21 in a Varicella Zoster Virus Glycoprotein E Subunit Vaccine

Luan, Ning; Cao, Han; Wang, Yunfei; Lin, Kangyang; Liu, Cunbao

doi:10.3390/pharmaceutics14050973

Cited by 7 publications

(5 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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.

View full text Add to dashboard Cite

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

show abstract

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.

View full text Add to dashboard Cite

show abstract

“…PMA + ionomycin (10 μg/mL, DAKEWE, Beijing, China) was added to the 96-well plates (Corning Inc., Corning, NY, USA) as a positive control. The cells were incubated overnight at 37 °C and 5% CO 2 , and the cell supernatants were collected to detect the levels of IL-2 and IFN-γ [ 22 ].…”

Section: Methodsmentioning

confidence: 99%

Comparison of the Immune Effects of an mRNA Vaccine and a Subunit Vaccine against Herpes Zoster Administered by Different Injection Methods

et al. 2023

Self Cite

View full text Add to dashboard Cite

Previous studies have shown that the herpes zoster subunit vaccine Shingrix™ performs well in clinical trials. However, the key ingredient in its adjuvant, QS21, is extracted from rare plants in South America, so vaccine production is limited. Compared with subunit vaccines, mRNA vaccines have the advantages of faster production and not requiring adjuvants, but currently, there is no authorized mRNA vaccine for herpes zoster. Therefore, this study focused on herpes zoster subunit and mRNA vaccines. We prepared a herpes zoster mRNA vaccine and compared the effects of vaccine type, immunization route, and adjuvant use on vaccine immunological efficacy. The mRNA vaccine was injected directly into mice via subcutaneous or intramuscular injection. The subunit vaccine was mixed with adjuvants before immunization. The adjuvants include B2Q or alum. B2Q is BW006S + 2395S + QS21. BW006S and 2395S are phosphodiester CpG oligodeoxynucleotides (CpG ODNs). Then, we compared the cell-mediated immunity (CIM) and humoral immunity levels of the different groups of mice. The results showed that the immune responses of mice inoculated with the mRNA vaccine prepared in this study were not significantly different from those of mice inoculated with the protein subunit vaccine supplemented with the B2Q. The mRNA vaccine-induced immune responses following subcutaneous or intramuscular injection, and the different immunization routes did not lead to significant differences in immune response intensity. Similar results were also observed for the protein subunit vaccine adjuvanted with B2Q but not alum. The above results suggest that our experiment can provide a reference for the preparation of mRNA vaccines against herpes zoster and has certain reference significance for the selection of the immunization route; that is, there is no significant difference in the immune response caused by subcutaneous versus an intramuscular injection, so the injection route can be determined according to the actual situation of individuals.

show abstract

“…These LNPs may improve the adjuvant effect of CpG oligodeoxynucleotides and QS21 on VZV‐gE, influencing both humoral immunity and CMI. These LNPs were used to create vaccinations that showed promise as varicella shots without the possibility of HZV, making them a unique kind of herpes zoster vaccination 87 (Figure 2, Table 2).…”

Section: Immunological Responses To Vzv Infectionmentioning

confidence: 99%

Varicella‐zoster virus‐related neurological complications: From infection to immunomodulatory therapies

Hakami,

Khan,

Abdulaziz

et al. 2024

Reviews in Medical Virology

View full text Add to dashboard Cite

The Varicella‐zoster virus (VZV), classified as a neurotropic member of the Herpesviridae family, exhibits a characteristic pathogenicity, predominantly inducing varicella, commonly known as chickenpox, during the initial infectious phase, and triggering the reactivation of herpes zoster, more commonly recognized as shingles, following its emergence from a latent state. The pathogenesis of VZV‐associated neuroinflammation involves a complex interplay between viral replication within sensory ganglia and immune‐mediated responses that contribute to tissue damage and dysfunction. Upon primary infection, VZV gains access to sensory ganglia, establishing latent infection within neurons. During reactivation, the virus can spread along sensory nerves, triggering a cascade of inflammatory mediators, chemokines, and immune cell infiltration in the affected neural tissues. The role of both adaptive and innate immune reactions, including the contributions of T and B cells, macrophages, and dendritic cells, in orchestrating the immune‐mediated damage in the central nervous system is elucidated. Furthermore, the aberrant activation of the natural defence mechanism, characterised by the dysregulated production of immunomodulatory proteins and chemokines, has been implicated in the pathogenesis of VZV‐induced neurological disorders, such as encephalitis, myelitis, and vasculopathy. The intricate balance between protective and detrimental immune responses in the context of VZV infection emphasises the necessity for an exhaustive comprehension of the immunopathogenic mechanisms propelling neuroinflammatory processes. Despite the availability of vaccines and antiviral therapies, VZV‐related neurological complications remain a significant concern, particularly in immunocompromised individuals and the elderly. Elucidating these mechanisms might facilitate the emergence of innovative immunomodulatory strategies and targeted therapies aimed at mitigating VZV‐induced neuroinflammatory damage and improving clinical outcomes. This comprehensive understanding enhances our grasp of viral pathogenesis and holds promise for pioneering therapeutic strategies designed to mitigate the neurological ramifications of VZV infections.

show abstract

Ionizable Lipid Nanoparticles Enhanced the Synergistic Adjuvant Effect of CpG ODNs and QS21 in a Varicella Zoster Virus Glycoprotein E Subunit Vaccine

Cited by 7 publications

References 58 publications

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

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

Comparison of the Immune Effects of an mRNA Vaccine and a Subunit Vaccine against Herpes Zoster Administered by Different Injection Methods

Varicella‐zoster virus‐related neurological complications: From infection to immunomodulatory therapies

Contact Info

Product

Resources

About