The Effect of a TLR4 Agonist/Cationic Liposome Adjuvant on Varicella-Zoster Virus Glycoprotein E Vaccine Efficacy: Antigen Presentation, Uptake, and Delivery to Lymph Nodes
Abstract:Adjuvant CIA09, composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)-based cationic liposomes and the toll-like receptor 4 agonist de-O-acylated lipooligosaccharide (dLOS), has been shown to enhance antibody and cellular immune responses to varicella-zoster virus (VZV) glycoprotein E (gE), recombinant tuberculosis vaccine antigen, and inactivated Japanese encephalitis vaccine. In this study, we investigated its modes of action using VZV gE as a model antigen. Liposomes adsorbed gE and cooperatively wit… Show more
“…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.…”
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
“…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.…”
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
“…dLOS-induced cytokine production in mouse peritoneal macrophages is comparable to MPLA but exhibits superior activation capabilities in human monocytes and DCs [ 114 ]. In preclinical animal studies, the adjuvant CIA09, comprising cationic liposomes and dLOS, effectively boosted antibody and cell-mediated immune responses against recombinant tuberculosis antigens, inactivated Japanese encephalitis vaccine (JEV), and recombinant varicella-zoster virus (VZV) glycoprotein E (gE) antigen [ 115 , 116 , 117 , 118 ].…”
Section: Enhancement Of Lbnp Vaccine Efficacy Via Toll-like Receptor ...mentioning
Infectious diseases are a predominant problem in human health. While the incidence of many pathogenic infections is controlled by vaccines, some pathogens still pose a challenging task for vaccine researchers. In order to face these challenges, the field of vaccine development has changed tremendously over the last few years. For non-replicating recombinant antigens, novel vaccine delivery systems that attempt to increase the immunogenicity by mimicking structural properties of pathogens are already approved for clinical applications. Lipid-based nanoparticles (LbNPs) of different natures are vesicles made of lipid layers with aqueous cavities, which may carry antigens and other biomolecules either displayed on the surface or encapsulated in the cavity. However, the efficacy profile of recombinant LbNP vaccines is not as high as that of live-attenuated ones. This review gives a compendious picture of two approaches that affect the immunogenicity of recombinant LbNP vaccines: (i) the incorporation of immunostimulatory agents and (ii) the utilization of pre-existing or promiscuous cellular immunity, which might be beneficial for the development of tailored prophylactic and therapeutic LbNP vaccine candidates.
“… 42 , 64 Further, as a carrier of nanovaccine, cationic liposomes have been notably acknowledged for better cellular uptake, antigen delivery and DCs initiation. 40 , 65 They are well-known DCs inducers and enhance expression of CD40, CD80, and CD86, resulting in the presentation of class I antigen and priming of antigen-specific CD8+ T cells. 26 , 66 Figure 2.…”
Section: Effect Of the Nanovaccines On Dcsmentioning
An attractive type of cancer immunotherapy is cancer therapeutic vaccines that induce antitumor immunity effectively. Although supportive results in the recent vaccine studies, there are still numerous drawbacks, such as poor stability, weak immunogenicity and strong toxicity, to be tackled for promoting the potency and durability of antitumor efficacy. NPs (Nanoparticles)-based vaccines offer unique opportunities to breakthrough the current bottleneck. As a rule, nanovaccines are new the generations of vaccines that use NPs as carriers and/or adjuvants. Several advantages of nanovaccines are constantly explored, including optimal nanometer size, high stability, plenty of antigen loading, enhanced immunogenicity, tunable antigen presentation, more retention in lymph nodes and promote patient compliance by a lower frequency of dosing. Here, we summarized the merits and highlight the diverse role nanovaccines play in improving antitumor responses.
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