Serving the Society Since 1986
Advanced Search
Volume 37 Issue 5
October 2022
    Citation: Ning Luan, Han Cao, Yunfei Wang, Kangyang Lin, Cunbao Liu. LNP-CpG ODN-adjuvanted varicella-zoster virus glycoprotein E induced comparable levels of immunity with ShingrixTM in VZV-primed mice .VIROLOGICA SINICA, 2022, 37(5) : 731-739.  http://dx.doi.org/10.1016/j.virs.2022.06.002
    shu

    LNP-CpG ODN-adjuvanted varicella-zoster virus glycoprotein E induced comparable levels of immunity with ShingrixTM in VZV-primed mice

    • Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China

    • Corresponding author: Cunbao Liu, cunbao_liu@163.com
    • Received Date: 02 March 2022
      Accepted Date: 01 June 2022
      Available online: 06 June 2022
    • Latent varicella-zoster virus (VZV) may be reactivated to cause herpes zoster, which affects one in three people during their lifetime. The currently available subunit vaccine ShingrixTM is superior to the attenuated vaccine Zostavax® in terms of both safety and efficacy, but the supply of its key adjuvant component QS21 is limited. With ionizable lipid nanoparticles (LNPs) that were recently approved by the FDA for COVID-19 mRNA vaccines as carriers, and oligodeoxynucleotides containing CpG motifs (CpG ODNs) approved by the FDA for a subunit hepatitis B vaccine as immunostimulators, we developed a LNP vaccine encapsulating VZV-glycoprotein E (gE) and CpG ODN, and compared its immunogenicity with ShingrixTM in C57BL/6J mice. The results showed that the LNP vaccine induced comparable levels of gE-specific IgG antibodies to ShingrixTM as determined by enzyme-linked immunosorbent assay (ELISA). Most importantly, the LNP vaccine induced comparable levels of cell-mediated immunity (CMI) that plays decisive roles in the efficacy of zoster vaccines to ShingrixTM in a VZV-primed mouse model that was adopted for preclinical studies of ShingrixTM. Number of IL-2 and IFN-γ secreting splenocytes and proportion of T helper 1 (Th1) cytokine-expressing CD4+ T cells in LNP-CpG-adjuvanted VZV-gE vaccinated mice were similar to that of ShingrixTM boosted mice. All of the components in this LNP vaccine can be artificially and economically synthesized in large quantities, indicating the potential of LNP-CpG-adjuvanted VZV-gE as a more cost-effective zoster vaccine.
    • 加载中

      1. Arruti, M., Pineiro, L.D., Salicio, Y., Cilla, G., Goenaga, M.A., Lopez de Munain, A., 2017.Incidence of varicella zoster virus infections of the central nervous system in the elderly:a large tertiary hospital-based series (2007-2014). J. Neurovirol. 23, 451-459.

      2. Arvin, A., 2005. Aging, immunity, and the varicella-zoster virus. N. Engl. J. Med. 352, 2266-2267.

      3. Asada, H., 2019. VZV-specific cell-mediated immunity, but not humoral immunity, correlates inversely with the incidence of herpes zoster and the severity of skin symptoms and zoster-associated pain:the SHEZ study. Vaccine 37, 6776-6781.

      4. Baxter, R., Ray, P., Tran, T.N., Black, S., Shinefield, H.R., Coplan, P.M., Lewis, E., Fireman, B., Saddier, P., 2013. Long-term effectiveness of varicella vaccine:a 14-Year, prospective cohort study. Pediatrics 131, e1389-1396.

      5. Berarducci, B., Ikoma, M., Stamatis, S., Sommer, M., Grose, C., Arvin, A.M., 2006.Essential functions of the unique N-terminal region of the varicella-zoster virus glycoprotein E ectodomain in viral replication and in the pathogenesis of skin infection. J. Virol. 80, 9481-9496.

      6. Breuer, J., 2018. Molecular genetic insights into varicella zoster virus (VZV), the vOka vaccine strain, and the pathogenesis of latency and reactivation. J. Infect. Dis. 218, S75-S80.

      7. Brewer, J.M., Pollock, K.G., Tetley, L., Russell, D.G., 2004. Vesicle size influences the trafficking, processing, and presentation of antigens in lipid vesicles. J. Immunol. 173, 6143-6150.

      8. Brewer, J.M., Tetley, L., Richmond, J., Liew, F.Y., Alexander, J., 1998. Lipid vesicle size determines the Th1 or Th2 response to entrapped antigen. J. Immunol. 161, 4000-4007.

      9. Cao, H., Wang, Y., Luan, N., Liu, C., 2021a. Immunogenicity of varicella-zoster virus glycoprotein E formulated with lipid nanoparticles and. Nucleic Immunostimulators in Mice. Vaccines (Basel) 9, 310.

      10. Cao, H., Yang, S., Wang, Y., Luan, N., Yin, X., Lin, K., Liu, C., 2021b. An established Th2-oriented response to an alum-adjuvanted SARS-CoV-2 subunit vaccine is not reversible by sequential immunization with nucleic acid-adjuvanted Th1-oriented subunit vaccines. Vaccines 9, 1261.

      11. Carstens, M.G., Camps, M.G., Henriksen-Lacey, M., Franken, K., Ottenhoff, T.H., Perrie, Y., Bouwstra, J.A., Ossendorp, F., Jiskoot, W., 2011. Effect of vesicle size on tissue localization and immunogenicity of liposomal DNA vaccines. Vaccine 29, 4761-4770.

      12. Chlibek, R., Bayas, J.M., Collins, H., de la Pinta, M.L., Ledent, E., Mols, J.F., Heineman, T.C., 2013. Safety and immunogenicity of an AS01-adjuvanted varicellazoster virus subunit candidate vaccine against herpes zoster in adults >=50 years of age. J. Infect. Dis. 208, 1953-1961.

      13. Cohen, J.I., 2015. A new vaccine to prevent herpes zoster. N. Engl. J. Med. 372, 2149-2150.

      14. Cunningham, A.L., Heineman, T.C., Lal, H., Godeaux, O., Chlibek, R., Hwang, S.J., McElhaney, J.E., Vesikari, T., Andrews, C., Choi, W.S., Esen, M., Ikematsu, H., Choma, M.K., Pauksens, K., Ravault, S., Salaun, B., Schwarz, T.F., Smetana, J., Abeele, C.V., Van den Steen, P., Vastiau, I., Weckx, L.Y., Levin, M.J., Group, Z.O.E.S., 2018. Immune responses to a recombinant glycoprotein E herpes zoster vaccine in adults aged 50 Years or older. J. Infect. Dis. 217, 1750-1760.

      15. Cunningham, A.L., Lal, H., Kovac, M., Chlibek, R., Hwang, S.J., Diez-Domingo, J., Godeaux, O., Levin, M.J., McElhaney, J.E., Puig-Barbera, J., Vanden Abeele, C., Vesikari, T., Watanabe, D., Zahaf, T., Ahonen, A., Athan, E., Barba-Gomez, J.F., Campora, L., de Looze, F., Downey, H.J., Ghesquiere, W., Gorfinkel, I., Korhonen, T., Leung, E., McNeil, S.A., Oostvogels, L., Rombo, L., Smetana, J., Weckx, L., Yeo, W., Heineman, T.C., Group, Z.O.E.S., 2016. Efficacy of the herpes zoster subunit vaccine in adults 70 Years of age or older. N. Engl. J. Med. 375, 1019-1032.

      16. Dendouga, N., Fochesato, M., Lockman, L., Mossman, S., Giannini, S.L., 2012. Cellmediated immune responses to a varicella-zoster virus glycoprotein E vaccine using both a TLR agonist and QS21 in mice. Vaccine 30, 3126-3135.

      17. Garcia-Valcarcel, M., Fowler, W.J., Harper, D.R., Jeffries, D.J., Layton, G.T., 1997.Induction of neutralizing antibody and T-cell responses to varicella-zoster virus (VZV) using Ty-virus-like particles carrying fragments of glycoprotein E (gE). Vaccine 15, 709-719.

      18. Gershon, A.A., Breuer, J., Cohen, J.I., Cohrs, R.J., Gershon, M.D., Gilden, D., Grose, C., Hambleton, S., Kennedy, P.G., Oxman, M.N., Seward, J.F., Yamanishi, K., 2015. Varicella zoster virus infection. Nat. Rev. Dis. Prim. 1, 15016.

      19. Gilbert, P.B., Gabriel, E.E., Miao, X., Li, X., Su, S.C., Parrino, J., Chan, I.S., 2014. Fold rise in antibody titers by measured by glycoprotein-based enzyme-linked immunosorbent assay is an excellent correlate of protection for a herpes zoster vaccine, demonstrated via the vaccine efficacy curve. J. Infect. Dis. 210, 1573-1581.

      20. Gilderman, L.I., Lawless, J.F., Nolen, T.M., Sterling, T., Rutledge, R.Z., Fernsler, D.A., Azrolan, N., Sutradhar, S.C., Wang, W.W., Chan, I.S., Schlienger, K., Schodel, F., Silber, J.L., Zostavax Protocol 010 Study, G., 2008. A double-blind, randomized, controlled, multicenter safety and immunogenicity study of a refrigerator-stable formulation of Zostavax. Clin. Vaccine Immunol. 15, 314-319.

      21. Haberthur, K., Engelmann, F., Park, B., Barron, A., Legasse, A., Dewane, J., Fischer, M., Kerns, A., Brown, M., Messaoudi, I., 2011. CD4 T cell immunity is critical for the control of simian varicella virus infection in a nonhuman primate model of VZV infection. PLoS Pathog. 7, e1002367.

      22. Hales, C.M., Harpaz, R., Joesoef, M.R., Bialek, S.R., 2013. Examination of links between herpes zoster incidence and childhood varicella vaccination. Ann. Intern. Med. 159, 739-745.

      23. Haumont, M., Jacquet, A., Massaer, M., Deleersnyder, V., Mazzu, P., Bollen, A., Jacobs, P., 1996. Purification, characterization and immunogenicity of recombinant varicellazoster virus glycoprotein gE secreted by Chinese hamster ovary cells. Virus Res. 40, 199-204.

      24. He, L., Sun, B., Guo, Y., Yan, K., Liu, D., Zang, Y., Jiang, C., Zhang, Y., Kong, W., 2021. Immune response of C57BL/6J mice to herpes zoster subunit vaccines formulated with nanoemulsion-based and liposome-based adjuvants. Int. Immunopharm. 101, 108216.

      25. Henriksen-Lacey, M., Devitt, A., Perrie, Y., 2011. The vesicle size of DDA:TDB liposomal adjuvants plays a role in the cell-mediated immune response but has no significant effect on antibody production. J. Contr. Release 154, 131-137.

      26. Hope-Simpson, R.E., 1965. The nature of herpes zoster:a long-term study and a new hypothesis. Proc. Roy. Soc. Med. 58, 9-20.

      27. Iqbal, M., Zafar, N., Fessi, H., Elaissari, A., 2015. Double emulsion solvent evaporation techniques used for drug encapsulation. Int. J. Pharm. 496, 173-190.

      28. Johnson, R.W., Rice, A.S., 2014. Clinical practice. Postherpetic neuralgia. N. Engl. J. Med. 371, 1526-1533.

      29. Krause, P.R., Klinman, D.M., 2000. Varicella vaccination:evidence for frequent reactivation of the vaccine strain in healthy children. Nat. Med. 6, 451-454.

      30. Laing, K.J., Russell, R.M., Dong, L., Schmid, D.S., Stern, M., Magaret, A., Haas, J.G., Johnston, C., Wald, A., Koelle, D.M., 2015. Zoster vaccination increases the breadth of CD4+ T cells responsive to varicella zoster virus. J. Infect. Dis. 212, 1022-1031.

      31. Lee, T., Suh, J., Choi, J.K., Lee, J., Park, S.H., 2021. Estimating the basic reproductive number of varicella in South Korea incorporating social contact patterns and seroprevalence. Hum. Vaccines Immunother. 17, 2488-2493.

      32. Leroux-Roels, I., Leroux-Roels, G., Clement, F., Vandepapeliere, P., Vassilev, V., Ledent, E., Heineman, T.C., 2012. A phase 1/2 clinical trial evaluating safety and immunogenicity of a varicella zoster glycoprotein e subunit vaccine candidate in young and older adults. J. Infect. Dis. 206, 1280-1290.

      33. Leung, J., Harpaz, R., Molinari, N.A., Jumaan, A., Zhou, F., 2011. Herpes zoster incidence among insured persons in the United States, 1993-2006:evaluation of impact of varicella vaccination. Clin. Infect. Dis. 52, 332-340.

      34. Levin, M.J., Bresnitz, E., Popmihajlov, Z., Weinberg, A., Liaw, K.L., Willis, E., Curtis, J.R., 2017. Studies with herpes zoster vaccines in immune compromised patients. Expert Rev. Vaccines 16, 1217-1230.

      35. Levin, M.J., Oxman, M.N., Zhang, J.H., Johnson, G.R., Stanley, H., Hayward, A.R., Caulfield, M.J., Irwin, M.R., Smith, J.G., Clair, J., Chan, I.S., Williams, H., Harbecke, R., Marchese, R., Straus, S.E., Gershon, A., Weinberg, A., Veterans Affairs Cooperative Studies Program Shingles Prevention Study, I., 2008. Varicella-zoster virus-specific immune responses in elderly recipients of a herpes zoster vaccine.J. Infect. Dis. 197, 825-835.

      36. Liu, C., Chu, X., Sun, P., Feng, X., Huang, W., Liu, H., Ma, Y., 2018a. Synergy effects of Polyinosinic-polycytidylic acid, CpG oligodeoxynucleotide, and cationic peptides to adjuvant HPV E7 epitope vaccine through preventive and therapeutic immunization in a TC-1 grafted mouse model. Hum. Vaccines Immunother. 14, 931-940.

      37. Liu, C., Chu, X., Yan, M., Qi, J., Liu, H., Gao, F., Gao, R., Ma, G., Ma, Y., 2018b.Encapsulation of Poly I:C and the natural phosphodiester CpG ODN enhanced the efficacy of a hyaluronic acid-modified cationic lipid-PLGA hybrid nanoparticle vaccine in TC-1-grafted tumors. Int. J. Pharm. 553, 327-337.

      38. Liu, C., Huang, P., Zhao, D., Xia, M., Zhong, W., Jiang, X., Tan, M., 2021. Effects of rotavirus NSP4 protein on the immune response and protection of the SR69A-VP8* nanoparticle rotavirus vaccine. Vaccine 39, 263-271.

      39. Mahalingam, R., Messaoudi, I., Gilden, D., 2010. Simian varicella virus pathogenesis. Curr. Top. Microbiol. Immunol. 342, 309-321.

      40. Malavige, G.N., Jones, L., Black, A.P., Ogg, G.S., 2008. Varicella zoster virus glycoprotein E-specific CD4+ T cells show evidence of recent activation and effector differentiation, consistent with frequent exposure to replicative cycle antigens in healthy immune donors. Clin. Exp. Immunol. 152, 522-531.

      41. Mo, C., Lee, J., Sommer, M., Grose, C., Arvin, A.M., 2002. The requirement of varicella zoster virus glycoprotein E (gE) for viral replication and effects of glycoprotein I on gE in melanoma cells. Virology 304, 176-186.

      42. Mo, C., Schneeberger, E.E., Arvin, A.M., 2000. Glycoprotein E of varicella-zoster virus enhances cell-cell contact in polarized epithelial cells. J. Virol. 74, 11377-11387.

      43. Moffat, J., Mo, C., Cheng, J.J., Sommer, M., Zerboni, L., Stamatis, S., Arvin, A.M., 2004. Functions of the C-terminal domain of varicella-zoster virus glycoprotein E in viral replication in vitro and skin and T-cell tropism in vivo. J. Virol. 78, 12406-12415.

      44. Monslow, M.A., Elbashir, S., Sullivan, N.L., Thiriot, D.S., Ahl, P., Smith, J., Miller, E., Cook, J., Cosmi, S., Thoryk, E., Citron, M., Thambi, N., Shaw, C., Hazuda, D., Vora, K.A., 2020. Immunogenicity generated by mRNA vaccine encoding VZV gE antigen is comparable to adjuvanted subunit vaccine and better than live attenuated vaccine in nonhuman primates. Vaccine 38, 5793-5802.

      45. Ogunjimi, B., Hens, N., Goeyvaerts, N., Aerts, M., Van Damme, P., Beutels, P., 2009. Using empirical social contact data to model person to person infectious disease transmission:an illustration for varicella. Math. Biosci. 218, 80-87.

      46. Oxman, M.N., Levin, M.J., Johnson, G.R., Schmader, K.E., Straus, S.E., Gelb, L.D., Arbeit, R.D., Simberkoff, M.S., Gershon, A.A., Davis, L.E., Weinberg, A., Boardman, K.D., Williams, H.M., Zhang, J.H., Peduzzi, P.N., Beisel, C.E., Morrison, V.A., Guatelli, J.C., Brooks, P.A., Kauffman, C.A., Pachucki, C.T., Neuzil, K.M., Betts, R.F., Wright, P.F., Griffin, M.R., Brunell, P., Soto, N.E., Marques, A.R., Keay, S.K., Goodman, R.P., Cotton, D.J., Gnann Jr., J.W., Loutit, J., Holodniy, M., Keitel, W.A., Crawford, G.E., Yeh, S.S., Lobo, Z., Toney, J.F., Greenberg, R.N., Keller, P.M., Harbecke, R., Hayward, A.R., Irwin, M.R., Kyriakides, T.C., Chan, C.Y., Chan, I.S., Wang, W.W., Annunziato, P.W., Silber, J.L., Shingles Prevention Study, G., 2005. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N. Engl. J. Med. 352, 2271-2284.

      47. Steain, M., Sutherland, J.P., Rodriguez, M., Cunningham, A.L., Slobedman, B., Abendroth, A., 2014. Analysis of T cell responses during active varicella-zoster virus reactivation in human ganglia. J. Virol. 88, 2704-2716.

      48. Takahashi, M., Otsuka, T., Okuno, Y., Asano, Y., Yazaki, T., 1974. Live vaccine used to prevent the spread of varicella in children in hospital. Lancet 2, 1288-1290.

      49. Upadhyay, S., Jeena, G.S., Shikha, Shukla, R.K., 2018. Recent advances in steroidal saponins biosynthesis and in vitro production. Planta 248, 519-544.

      50. Wang, P., 2021. Natural and synthetic saponins as vaccine adjuvants. Vaccines 9, 222.

      51. Wang, Y., Qi, J., Cao, H., Liu, C., 2021. Immune responses to varicella-zoster virus glycoprotein E formulated with poly(lactic-co-glycolic acid) nanoparticles and nucleic acid adjuvants in mice. Virol. Sin. 36, 122-132.

      52. Weinberg, A., Levin, M.J., 2010. VZV T cell-mediated immunity. Curr. Top. Microbiol.Immunol. 342, 341-357.

      53. Wroblewska, Z., Valyi-Nagy, T., Otte, J., Dillner, A., Jackson, A., Sole, D.P., Fraser, N.W., 1993. A mouse model for varicella-zoster virus latency. Microb. Pathog. 15, 141-151.

      54. Wui, S.R., Kim, K.S., Ryu, J.I., Ko, A., Do, H.T.T., Lee, Y.J., Kim, H.J., Lim, S.J., Park, S.A., Cho, Y.J., Kim, C.G., Lee, N.G., 2019. Efficient induction of cell-mediated immunity to varicella-zoster virus glycoprotein E co-lyophilized with a cationic liposome-based adjuvant in mice. Vaccine 37, 2131-2141.

      55. Zhu, R., Liu, J., Chen, C., Ye, X., Xu, L., Wang, W., Zhao, Q., Zhu, H., Cheng, T., Xia, N., 2016. A highly conserved epitope-vaccine candidate against varicella-zoster virus induces neutralizing antibodies in mice. Vaccine 34, 1589-1596.

    • 加载中
    PDF

    Article Metrics

    Article views(2495) PDF downloads(15) Cited by()

    Related
    Proportional views

      LNP-CpG ODN-adjuvanted varicella-zoster virus glycoprotein E induced comparable levels of immunity with ShingrixTM in VZV-primed mice

        Corresponding author: Cunbao Liu, cunbao_liu@163.com
      • Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China
      • Received Date: 02 March 2022
      • Accepted Date: 01 June 2022

      Abstract: Latent varicella-zoster virus (VZV) may be reactivated to cause herpes zoster, which affects one in three people during their lifetime. The currently available subunit vaccine ShingrixTM is superior to the attenuated vaccine Zostavax® in terms of both safety and efficacy, but the supply of its key adjuvant component QS21 is limited. With ionizable lipid nanoparticles (LNPs) that were recently approved by the FDA for COVID-19 mRNA vaccines as carriers, and oligodeoxynucleotides containing CpG motifs (CpG ODNs) approved by the FDA for a subunit hepatitis B vaccine as immunostimulators, we developed a LNP vaccine encapsulating VZV-glycoprotein E (gE) and CpG ODN, and compared its immunogenicity with ShingrixTM in C57BL/6J mice. The results showed that the LNP vaccine induced comparable levels of gE-specific IgG antibodies to ShingrixTM as determined by enzyme-linked immunosorbent assay (ELISA). Most importantly, the LNP vaccine induced comparable levels of cell-mediated immunity (CMI) that plays decisive roles in the efficacy of zoster vaccines to ShingrixTM in a VZV-primed mouse model that was adopted for preclinical studies of ShingrixTM. Number of IL-2 and IFN-γ secreting splenocytes and proportion of T helper 1 (Th1) cytokine-expressing CD4+ T cells in LNP-CpG-adjuvanted VZV-gE vaccinated mice were similar to that of ShingrixTM boosted mice. All of the components in this LNP vaccine can be artificially and economically synthesized in large quantities, indicating the potential of LNP-CpG-adjuvanted VZV-gE as a more cost-effective zoster vaccine.

        HTML

      Reference (55) Relative (20)

      目录

      This journal is a member of, and subscribes to the principles of, the Committee on Publication Ethics (COPE)

      鄂ICP备05001977号

         

      鄂公网安备 42010602003674号

      Copyright © 2019 Virologica Sinica. All rights reserved

      /

      DownLoad:  Full-Size Img  PowerPoint
      Return
      Return