1887

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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2010-06-01
2019-11-13
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References

  1. Appaiahgari, M. B. & Vrati, S. ( 2004; ). Immunogenicity and protective efficacy in mice of a formaldehyde-inactivated Indian strain of Japanese encephalitis virus grown in Vero cells. Vaccine 22, 3669–3675.[CrossRef]
    [Google Scholar]
  2. Barrett, A. D. & Gould, E. A. ( 1986; ). Comparison of neurovirulence of different strains of yellow fever virus in mice. J Gen Virol 67, 631–637.[CrossRef]
    [Google Scholar]
  3. Beasley, D. W., Lewthwaite, P. & Solomon, T. ( 2008; ). Current use and development of vaccines for Japanese encephalitis. Expert Opin Biol Ther 8, 95–106.[CrossRef]
    [Google Scholar]
  4. Broom, A. K., Wallace, M. J., Mackenzie, J. S., Smith, D. W. & Hall, R. A. ( 2000; ). Immunization with gamma globulin of Murray Valley encephalitis virus and with an inactivated Japanese encephalitis virus vaccine as prophylaxis against Australian encephalitis: evaluation in a mouse model. J Med Virol 61, 259–265.[CrossRef]
    [Google Scholar]
  5. Chu, J. H., Chiang, C. C. & Ng, M. L. ( 2007; ). Immunization of flavivirus West Nile recombinant envelope domain III protein induced specific immune response and protection against West Nile virus infection. J Immunol 178, 2699–2705.[CrossRef]
    [Google Scholar]
  6. Colombage, G., Hall, R., Pavy, M. & Lobigs, M. ( 1998; ). DNA-based and alphavirus-vectored immunisation with prM and E proteins elicits long-lived and protective immunity against the flavivirus, Murray Valley encephalitis virus. Virology 250, 151–163.[CrossRef]
    [Google Scholar]
  7. Coutelier, J. P., van der Logt, J. T., Heessen, F. W., Warnier, G. & Van Snick, J. ( 1987; ). IgG2a restriction of murine antibodies elicited by viral infections. J Exp Med 165, 64–69.[CrossRef]
    [Google Scholar]
  8. Ferguson, M., Kurane, I., Wimalaratne, O., Shin, J. & Wood, D. ( 2007; ). WHO informal consultation on the scientific basis of specifications for production and control of inactivated Japanese encephalitis vaccines for human use, Geneva, Switzerland, 1–2 June 2006. Vaccine 25, 5233–5243.[CrossRef]
    [Google Scholar]
  9. Ferguson, M., Johnes, S., Li, L., Heath, A. & Barrett, A. ( 2008; ). Effect of genomic variation in the challenge virus on the neutralization titres of recipients of inactivated JE vaccines – report of a collaborative study on PRNT50 assays for Japanese encephalitis virus (JE) antibodies. Biologicals 36, 111–116.[CrossRef]
    [Google Scholar]
  10. Fischer, M., Casey, C. & Chen, R. T. ( 2007; ). Promise of new Japanese encephalitis vaccines. Lancet 370, 1806–1808.[CrossRef]
    [Google Scholar]
  11. Goverdhan, M. K., Kulkarni, A. B., Gupta, A. K., Tupe, C. D. & Rodrigues, J. J. ( 1992; ). Two-way cross-protection between West Nile and Japanese encephalitis viruses in bonnet macaques. Acta Virol 36, 277–283.
    [Google Scholar]
  12. Gupta, R. K. ( 1998; ). Aluminum compounds as vaccine adjuvants. Adv Drug Deliv Rev 32, 155–172.[CrossRef]
    [Google Scholar]
  13. Halstead, S. B. ( 2003; ). Neutralization and antibody-dependent enhancement of dengue viruses. Adv Virus Res 60, 421–467.
    [Google Scholar]
  14. Halstead, S. B. & Tsai, T. F. ( 2004; ). Japanese encephalitis vaccines. In Vaccines, 4th edn, pp. 919–958. Edited by S. A. Plotkin & W. A. Orenstein. Philadelphia: Saunders.
  15. Hammon, W. M. & Sather, G. E. ( 1956; ). Immunity of hamsters to West Nile and Murray Valley viruses following immunization with St Louis and Japanese B. Proc Soc Exp Biol Med 91, 521–524.[CrossRef]
    [Google Scholar]
  16. Hawkes, R. A. ( 1964; ). Enhancement of the infectivity of arboviruses by specific antisera produced in domestic fowls. Aust J Exp Biol Med Sci 42, 465–482.[CrossRef]
    [Google Scholar]
  17. Hoke, C. H., Nisalak, A., Sangawhipa, N., Jatanasen, S., Laorakapongse, T., Innis, B. L., Kotchasenee, S., Gingrich, J. B., Latendresse, J. & other authors ( 1988; ). Protection against Japanese encephalitis by inactivated vaccines. N Engl J Med 319, 608–614.[CrossRef]
    [Google Scholar]
  18. Hombach, J., Solomon, T., Kurane, I., Jacobson, J. & Wood, D. ( 2005; ). Report on a WHO consultation on immunological endpoints for evaluation of new Japanese encephalitis vaccines, WHO, Geneva, 2–3 September, 2004. Vaccine 23, 5205–5211.[CrossRef]
    [Google Scholar]
  19. Huber, V. C., McKeon, R. M., Brackin, M. N., Miller, L. A., Keating, R., Brown, S. A., Makarova, N., Perez, D. R., Macdonald, G. H. & other authors ( 2006; ). Distinct contributions of vaccine-induced immunoglobulin G1 (IgG1) and IgG2a antibodies to protective immunity against influenza. Clin Vaccine Immunol 13, 981–990.[CrossRef]
    [Google Scholar]
  20. Huisman, W., Martina, B. E., Rimmelzwaan, G. F., Gruters, R. A. & Osterhaus, A. D. ( 2009; ). Vaccine-induced enhancement of viral infections. Vaccine 27, 505–512.[CrossRef]
    [Google Scholar]
  21. Kanesa-Thasan, N., Putnak, J. R., Mangiafico, J. A., Saluzzo, J. E. & Ludwig, G. V. ( 2002; ). Short report: absence of protective neutralizing antibodies to West Nile virus in subjects following vaccination with Japanese encephalitis or dengue vaccines. Am J Trop Med Hyg 66, 115–116.
    [Google Scholar]
  22. Konishi, E. & Suzuki, T. ( 2002; ). Ratios of subclinical to clinical Japanese encephalitis (JE) virus infections in vaccinated populations: evaluation of an inactivated JE vaccine by comparing the ratios with those in unvaccinated populations. Vaccine 21, 98–107.[CrossRef]
    [Google Scholar]
  23. Kuzuhara, S., Nakamura, H., Hayashida, K., Obata, J., Abe, M., Sonoda, K., Nishiyama, K., Sugawara, K., Takeda, K. & other authors ( 2003; ). Non-clinical and phase I clinical trials of a Vero cell-derived inactivated Japanese encephalitis vaccine. Vaccine 21, 4519–4526.[CrossRef]
    [Google Scholar]
  24. Licon Luna, R. M., Lee, E., Müllbacher, A., Blanden, R. V., Langman, R. & Lobigs, M. ( 2002; ). Lack of both Fas ligand and perforin protects from flavivirus-mediated encephalitis in mice. J Virol 76, 3202–3211.[CrossRef]
    [Google Scholar]
  25. Lobigs, M., Pavy, M. & Hall, R. A. ( 2003; ). Cross-protective and infection-enhancing immunity in mice vaccinated against flaviviruses belonging to the Japanese encephalitis virus serocomplex. Vaccine 21, 1572–1579.[CrossRef]
    [Google Scholar]
  26. Lobigs, M., Larena, M., Alsharifi, M., Lee, E. & Pavy, M. ( 2009; ). Live chimeric and inactivated Japanese encephalitis virus vaccines differ in their cross-protective values against Murray Valley encephalitis virus. J Virol 83, 2436–2445.[CrossRef]
    [Google Scholar]
  27. Mackenzie, J. S., Gubler, D. J. & Petersen, L. R. ( 2004; ). Emerging flaviviruses: the spread and resurgence of Japanese encephalitis, West Nile and dengue viruses. Nat Med 10, S98–S109.[CrossRef]
    [Google Scholar]
  28. Markine-Goriaynoff, D. & Coutelier, J. P. ( 2002; ). Increased efficacy of the immunoglobulin G2a subclass in antibody-mediated protection against lactate dehydrogenase-elevating virus-induced polioencephalomyelitis revealed with switch mutants. J Virol 76, 432–435.[CrossRef]
    [Google Scholar]
  29. Martin, R. M., Brady, J. L. & Lew, A. M. ( 1998; ). The need for IgG2c specific antiserum when isotyping antibodies from C57BL/6 and NOD mice. J Immunol Methods 212, 187–192.[CrossRef]
    [Google Scholar]
  30. Martina, B. E., Koraka, P., van den Doel, P., van Amerongen, G., Rimmelzwaan, G. F. & Osterhaus, A. D. ( 2008; ). Immunization with West Nile virus envelope domain III protects mice against lethal infection with homologous and heterologous virus. Vaccine 26, 153–157.[CrossRef]
    [Google Scholar]
  31. McKee, A. S., Munks, M. W. & Marrack, P. ( 2007; ). How do adjuvants work? Important considerations for new generation adjuvants. Immunity 27, 687–690.[CrossRef]
    [Google Scholar]
  32. Moghaddam, A., Olszewska, W., Wang, B., Tregoning, J. S., Helson, R., Sattentau, Q. J. & Openshaw, P. J. ( 2006; ). A potential molecular mechanism for hypersensitivity caused by formalin-inactivated vaccines. Nat Med 12, 905–907.[CrossRef]
    [Google Scholar]
  33. Monath, T. P. ( 2002a; ). Japanese encephalitis vaccines: current vaccines and future prospects. Curr Top Microbiol Immunol 267, 105–138.
    [Google Scholar]
  34. Monath, T. P. ( 2002b; ). Editorial: Jennerian vaccination against West Nile virus. Am J Trop Med Hyg 66, 113–114.
    [Google Scholar]
  35. Monath, T. P., Guirakhoo, F., Nichols, R., Yoksan, S., Schrader, R., Murphy, C., Blum, P., Woodward, S., McCarthy, K. & other authors ( 2003; ). Chimeric live, attenuated vaccine against Japanese encephalitis (ChimeriVax-JE): phase 2 clinical trials for safety and immunogenicity, effect of vaccine dose and schedule, and memory response to challenge with inactivated Japanese encephalitis antigen. J Infect Dis 188, 1213–1230.[CrossRef]
    [Google Scholar]
  36. Mullbacher, A., Lobigs, M. & Lee, E. ( 2003; ). Immunobiology of mosquito-borne encephalitic flaviviruses. Adv Virus Res 60, 87–120.
    [Google Scholar]
  37. Nimmerjahn, F. & Ravetch, J. V. ( 2005; ). Divergent immunoglobulin G subclass activity through selective Fc receptor binding. Science 310, 1510–1512.[CrossRef]
    [Google Scholar]
  38. Petrovsky, N. ( 2006; ). Novel human polysaccharide adjuvants with dual Th1 and Th2 potentiating activity. Vaccine 24 (Suppl. 2), 26–29.
    [Google Scholar]
  39. Petrovsky, N. ( 2008; ). Freeing vaccine adjuvants from dangerous immunological dogma. Expert Rev Vaccines 7, 7–10.[CrossRef]
    [Google Scholar]
  40. Polack, F. P. ( 2007; ). Atypical measles and enhanced respiratory syncytial virus disease (ERD) made simple. Pediatr Res 62, 111–115.[CrossRef]
    [Google Scholar]
  41. Poland, J. D., Cropp, C. B., Craven, R. B. & Monath, T. P. ( 1990; ). Evaluation of the potency and safety of inactivated Japanese encephalitis vaccine in US inhabitants. J Infect Dis 161, 878–882.[CrossRef]
    [Google Scholar]
  42. Ranasinghe, C. & Ramshaw, I. A. ( 2009; ). Genetic heterologous prime–boost vaccination strategies for improved systemic and mucosal immunity. Expert Rev Vaccines 8, 1171–1181.[CrossRef]
    [Google Scholar]
  43. Silva, D. G., Cooper, P. D. & Petrovsky, N. ( 2004; ). Inulin-derived adjuvants efficiently promote both Th1 and Th2 immune responses. Immunol Cell Biol 82, 611–616.[CrossRef]
    [Google Scholar]
  44. Solomon, T. ( 2004; ). Flavivirus encephalitis. N Engl J Med 351, 370–378.[CrossRef]
    [Google Scholar]
  45. Srivastava, A. K., Putnak, J. R., Lee, S. H., Hong, S. P., Moon, S. B., Barvir, D. A., Zhao, B., Olson, R. A., Kim, S. O. & other authors ( 2001; ). A purified inactivated Japanese encephalitis virus vaccine made in Vero cells. Vaccine 19, 4557–4565.[CrossRef]
    [Google Scholar]
  46. Sugawara, K., Nishiyama, K., Ishikawa, Y., Abe, M., Sonoda, K., Komatsu, K., Horikawa, Y., Takeda, K., Honda, T. & other authors ( 2002; ). Development of Vero cell-derived inactivated Japanese encephalitis vaccine. Biologicals 30, 303–314.[CrossRef]
    [Google Scholar]
  47. Takasaki, T., Yabe, S., Nerome, R., Ito, M., Yamada, K. & Kurane, I. ( 2003; ). Partial protective effect of inactivated Japanese encephalitis vaccine on lethal West Nile virus infection in mice. Vaccine 21, 4514–4518.[CrossRef]
    [Google Scholar]
  48. Tang, F., Zhang, J. S., Liu, W., Zhao, Q. M., Zhang, F., Wu, X. M., Yang, H., Ly, H. & Cao, W. C. ( 2008; ). Failure of Japanese encephalitis vaccine and infection in inducing neutralizing antibodies against West Nile virus, People's Republic of China. Am J Trop Med Hyg 78, 999–1001.
    [Google Scholar]
  49. Tauber, E., Kollaritsch, H., Korinek, M., Rendi-Wagner, P., Jilma, B., Firbas, C., Schranz, S., Jong, E., Klingler, A. & other authors ( 2007; ). Safety and immunogenicity of a Vero-cell-derived, inactivated Japanese encephalitis vaccine: a non-inferiority, phase III, randomised controlled trial. Lancet 370, 1847–1853.[CrossRef]
    [Google Scholar]
  50. Toriniwa, H. & Komiya, T. ( 2008; ). Long-term stability of Vero cell-derived inactivated Japanese encephalitis vaccine prepared using serum-free medium. Vaccine 26, 3680–3689.[CrossRef]
    [Google Scholar]
  51. Tsai, T. F., Popovici, F., Cernescu, C., Campbell, G. L. & Nedelcu, N. I. ( 1998; ). West Nile encephalitis epidemic in southeastern Romania. Lancet 352, 767–771.[CrossRef]
    [Google Scholar]
  52. Wallace, M. J., Smith, D. W., Broom, A. K., Mackenzie, J. S., Hall, R. A., Shellam, G. R. & McMinn, P. C. ( 2003; ). Antibody-dependent enhancement of Murray Valley encephalitis virus virulence in mice. J Gen Virol 84, 1723–1728.[CrossRef]
    [Google Scholar]
  53. Williams, D. T., Daniels, P. W., Lunt, R. A., Wang, L. F., Newberry, K. M. & Mackenzie, J. S. ( 2001; ). Experimental infections of pigs with Japanese encephalitis virus and closely related Australian flaviviruses. Am J Trop Med Hyg 65, 379–387.
    [Google Scholar]
  54. Yang, K. D., Yeh, W. T., Yang, M. Y., Chen, R. F. & Shaio, M. F. ( 2001; ). Antibody-dependent enhancement of heterotypic dengue infections involved in suppression of IFNγ production. J Med Virol 63, 150–157.[CrossRef]
    [Google Scholar]
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