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The Journal of general virology2010; 91(Pt 6); 1407-1417; doi: 10.1099/vir.0.019190-0

An inactivated Vero cell-grown Japanese encephalitis vaccine formulated with Advax, a novel inulin-based adjuvant, induces protective neutralizing antibody against homologous and heterologous flaviviruses.

Abstract: Advax is a polysaccharide-based adjuvant that potently stimulates vaccine immunogenicity without the increased reactogenicity seen with other adjuvants. This study investigated the immunogenicity of a novel Advax-adjuvanted Vero cell culture candidate vaccine against Japanese encephalitis virus (JEV) in mice and horses. The results showed that, in mice, a two-immunization, low-dose (50 ng JEV antigen) regimen with adjuvanted vaccine produced solid neutralizing immunity comparable to that elicited with live ChimeriVax-JE immunization and superior to that elicited with tenfold higher doses of a traditional non-adjuvanted JEV vaccine (JE-VAX; Biken Institute) or a newly approved alum-adjuvanted vaccine (Jespect; Novartis). Mice vaccinated with the Advax-adjuvanted, but not the unadjuvanted vaccine, were protected against live JEV challenge. Equine immunizations against JEV with Advax-formulated vaccine similarly showed enhanced vaccine immunogenicity, confirming that the adjuvant effects of Advax are not restricted to rodent models. Advax-adjuvanted JEV vaccine elicited a balanced T-helper 1 (Th1)/Th2 immune response against JEV with protective levels of cross-neutralizing antibody against other viruses belonging to the JEV serocomplex, including Murray Valley encephalitis virus (MVEV). The adjuvanted JEV vaccine was well tolerated with minimal reactogenicity and no systemic toxicity in immunized animals. The cessation of manufacture of traditional mouse brain-derived unadjuvanted JEV vaccine in Japan has resulted in a JEV vaccine shortage internationally. There is also an ongoing lack of human vaccines against other JEV serocomplex flaviviruses, such as MVEV, making this adjuvanted, cell culture-grown JEV vaccine a promising candidate to address both needs with one vaccine.
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Publication Date: 2010-02-03 PubMed ID: 20130134PubMed Central: PMC2888167DOI: 10.1099/vir.0.019190-0Google Scholar: Lookup
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  • N.I.H.
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study discusses the enhanced potential of a new vaccine called Advax-adjuvanted Vero cell culture candidate against Japanese encephalitis virus (JEV) in mice and horses. It shows that this vaccine can induce a strong immune response at much lower doses than traditional JEV vaccines and provides broad protection against JEV and related viruses.

Aims and Methods of the Study

  • The primary aim of this study was to investigate the immunogenicity, or the ability of a vaccine to stimulate an immune response, of a new Japanese encephalitis virus (JEV) vaccine called Advax-adjuvanted Vero cell culture candidate.
  • The researchers carried out the study on mice and horses, using different doses of the Advax-adjuvanted vaccine and comparing it with other JEV vaccines such as ChimeriVax-JE, JE-VAX, and Jespect.
  • They also examined the survival rates of mice post live JEV exposure and the immunogenicity of the Advax-adjuvanted vaccine in horses to confirm its effectiveness in different animal models.
  • The study further explored the vaccine’s ability to elicit a balanced T-helper 1 (Th1)/Th2 immune response against JEV and related viruses.

Key Findings of the Study

  • The study found that the Advax-adjuvanted vaccine could induce a robust neutralizing immunity in mice, similar to live ChimeriVax-JE immunization and superior to traditional non-adjuvanted JEV vaccines (JE-VAX) or alum-adjuvanted vaccines (Jespect).
  • Only mice vaccinated with the Advax-adjuvanted vaccine survived live JEV challenge, demonstrating its potential protective capability.
  • The effectiveness of the Advax-adjuvanted JEV vaccine was also confirmed in horses, establishing the broader relevance of the vaccine across species.
  • The vaccine elicited a balanced Th1/Th2 immune response and provided protective levels of cross-neutralizing antibody against other viruses belonging to the JEV serocomplex such as the Murray Valley encephalitis virus (MVEV).
  • The Advax-adjuvanted JEV vaccine was well tolerated with minimal side effects and no systemic toxicity observed in immunized animals.

Significance and Implications

  • The findings of this study are significant as they reveal the promising potential of the Advax-adjuvanted vaccine in addressing the global shortage of traditional mouse-brain derived unadjuvanted JEV vaccines and the lack of human vaccines for other JEV serocomplex flaviviruses like MVEV.
  • The study establishes that Advax, as an adjuvant, is capable of enhancing the efficacy of a JEV vaccine at much lower doses, without increasing adverse reactions.
  • Thus, the Advax-adjuvanted Vero cell culture candidate vaccine for JEV could be a key solution to address the unmet need for effective and well-tolerated vaccines against Japanese encephalitis and related diseases.

Cite This Article

APA
Lobigs M, Pavy M, Hall RA, Lobigs P, Cooper P, Komiya T, Toriniwa H, Petrovsky N. (2010). An inactivated Vero cell-grown Japanese encephalitis vaccine formulated with Advax, a novel inulin-based adjuvant, induces protective neutralizing antibody against homologous and heterologous flaviviruses. J Gen Virol, 91(Pt 6), 1407-1417. https://doi.org/10.1099/vir.0.019190-0

Publication

The Journal of general virology
ISSN: 1465-2099
NlmUniqueID: 0077340
Country: England
Language: English
Volume: 91
Issue: Pt 6
Pages: 1407-1417

Researcher Affiliations

Lobigs, Mario
  • John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia. Mario.Lobigs@anu.edu.au
Pavy, Megan
    Hall, Roy A
      Lobigs, Päivi
        Cooper, Peter
          Komiya, Tomoyoshi
            Toriniwa, Hiroko
              Petrovsky, Nikolai

                MeSH Terms

                • Adjuvants, Immunologic / administration & dosage
                • Animals
                • Antibodies, Neutralizing / blood
                • Antibodies, Viral / blood
                • Chlorocebus aethiops
                • Cross Reactions
                • Encephalitis, Japanese / prevention & control
                • Female
                • Flavivirus / immunology
                • Horses
                • Inulin / administration & dosage
                • Inulin / analogs & derivatives
                • Japanese Encephalitis Vaccines / administration & dosage
                • Japanese Encephalitis Vaccines / immunology
                • Mice
                • Mice, Inbred BALB C
                • Mice, Inbred C57BL
                • Survival Analysis
                • Th1 Cells / immunology
                • Th2 Cells / immunology
                • Vaccination / methods
                • Vaccines, Inactivated / administration & dosage
                • Vaccines, Inactivated / immunology
                • Vero Cells

                Grant Funding

                • HHSN272200800039C / NIAID NIH HHS
                • U01 AI061142 / NIAID NIH HHS
                • U01-AI061142 / NIAID NIH HHS

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                48. Li L, Saade F, Petrovsky N. The future of human DNA vaccines. J Biotechnol 2012 Dec 31;162(2-3):171-82.
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                50. Gordon DL, Sajkov D, Woodman RJ, Honda-Okubo Y, Cox MM, Heinzel S, Petrovsky N. Randomized clinical trial of immunogenicity and safety of a recombinant H1N1/2009 pandemic influenza vaccine containing Advax™ polysaccharide adjuvant. Vaccine 2012 Aug 3;30(36):5407-16.
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                54. Layton RC, Petrovsky N, Gigliotti AP, Pollock Z, Knight J, Donart N, Pyles J, Harrod KS, Gao P, Koster F. Delta inulin polysaccharide adjuvant enhances the ability of split-virion H5N1 vaccine to protect against lethal challenge in ferrets. Vaccine 2011 Aug 26;29(37):6242-51.
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                57. Cristillo AD, Ferrari MG, Hudacik L, Lewis B, Galmin L, Bowen B, Thompson D, Petrovsky N, Markham P, Pal R. Induction of mucosal and systemic antibody and T-cell responses following prime-boost immunization with novel adjuvanted human immunodeficiency virus-1-vaccine formulations. J Gen Virol 2011 Jan;92(Pt 1):128-40.
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                58. Cooper PD, Petrovsky N. Delta inulin: a novel, immunologically active, stable packing structure comprising β-D-[2 -> 1] poly(fructo-furanosyl) α-D-glucose polymers. Glycobiology 2011 May;21(5):595-606.
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