Immunisation with gamma globulin to Murray Valley encephalitis virus and with an inactivated Japanese encephalitis virus vaccine as prophylaxis against Australian encephalitis: Evaluation in a mouse model

In northwestern Australia, the flavivirus Murray Valley encephalitis (MVE) poses a significant health risk to infants in some aboriginal communities, particularly during each wet season. While there are too few cases to warrant the development of a vaccine against MVE, a safe, effective prophylaxis for these children is still urgently required. The use of passive transfer of human gamma globulin to MVE or immunisation with a vaccine to the closely related Japanese encephalitis (JE) virus were investigated as potential strategies. When 40 μg of IgG was purified from MVE‐immune human sera and transferred to 3‐week‐old mice, the animals were protected from lethal IP inoculation with MVE virus while still producing a detectable immune response to the virus. Similarly, sera from adult mice infected sublethally with MVE or JE virus provided significant protection against MVE infection. However, sera from mice sublethally infected with the related Kunjin or immunised with the inactivated JE vaccine (Biken) provided no protection against MVE challenge. In fact, mice immunised passively with the latter appeared to succumb to MVE challenge more rapidly than mice that received serum from unimmunised animals, suggesting that antibody to the vaccine had accelerated the progression of disease. These preliminary trials in mice indicate that passive immunisation with human gamma globulin has the greatest potential as a strategy for MVE prophylaxis, whilst the apparent enhancement of MVE by antibodies to the JE vaccine requires further investigation, with particular reference to current vaccination programs in areas of Australia and Papua New Guinea, where both JE and MVE occur. J. Med. Virol. 61:259–265, 2000. © 2000 Wiley‐Liss, Inc.

[1]  R. Hall,et al.  DNA-based and alphavirus-vectored immunisation with prM and E proteins elicits long-lived and protective immunity against the flavivirus, Murray Valley encephalitis virus. , 1998, Virology.

[2]  A. Pronin,et al.  Immunological basis for protection in a murine model of tick-borne encephalitis by a recombinant adenovirus carrying the gene encoding the NS1 non-structural protein. , 1998, The Journal of general virology.

[3]  M. Eibl,et al.  Pre- and postexposure protection by passive immunoglobulin but no enhancement of infection with a flavivirus in a mouse model , 1997, Journal of virology.

[4]  S. Ritchie,et al.  An outbreak of Japanese encephalitis in the Torres Strait, Australia, 1995 , 1996, Medical Journal of Australia.

[5]  M. J. Howard,et al.  Protective immune responses to the E and NS1 proteins of Murray Valley encephalitis virus in hybrids of flavivirus-resistant mice. , 1996, The Journal of general virology.

[6]  D. Nadal,et al.  Tickborne encephalitis despite specific immunoglobulin prophylaxis , 1995, The Lancet.

[7]  M. J. Howard,et al.  Immunodominant epitopes on the NS1 protein of MVE and KUN viruses serve as targets for a blocking ELISA to detect virus-specific antibodies in sentinel animal serum. , 1995, Journal of virological methods.

[8]  J. Mackenzie,et al.  Mapping the Flv locus controlling resistance to flaviviruses on mouse chromosome 5 , 1994, Journal of virology.

[9]  David W Smith,et al.  Australian Encephalitis in Western Australia, 1978–1991 , 1993, The Medical journal of Australia.

[10]  J. Mackenzie,et al.  Immunoaffinity purification of the NS1 protein of Murray Valley encephalitis virus: selection of the appropriate ligand and optimal conditions for elution. , 1991, Journal of virological methods.

[11]  S. Halstead,et al.  Measurement of antibody-dependent infection enhancement of four dengue virus serotypes by monoclonal and polyclonal antibodies. , 1990, The Journal of general virology.

[12]  E. Gould,et al.  Antibody-dependent enhancement of yellow fever and Japanese encephalitis virus neurovirulence. , 1989, The Journal of general virology.

[13]  A. Barrett,et al.  Antibody-mediated early death in vivo after infection with yellow fever virus. , 1986, The Journal of general virology.

[14]  A. Barrett,et al.  Neutralizing (54K) and non-neutralizing (54K and 48K) monoclonal antibodies against structural and non-structural yellow fever virus proteins confer immunity in mice. , 1986, The Journal of general virology.

[15]  J. Schlesinger,et al.  Protection against 17D yellow fever encephalitis in mice by passive transfer of monoclonal antibodies to the nonstructural glycoprotein gp48 and by active immunization with gp48. , 1985, Journal of immunology.

[16]  S. Halstead,et al.  Enhancement of dengue virus infection in monocytes by flavivirus antisera. , 1980, The American journal of tropical medicine and hygiene.

[17]  J. S. Porterfield,et al.  Antibody-mediated enhancement of Flavivirus replication in macrophage-like cell lines , 1979, Nature.

[18]  SB Halstead,et al.  Dengue viruses and mononuclear phagocytes. I. Infection enhancement by non-neutralizing antibody , 1977, The Journal of experimental medicine.

[19]  J. S. Porterfield,et al.  The flaviviruses (group B arboviruses): a cross-neutralization study. , 1974, The Journal of general virology.

[20]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[21]  K. Lafferty,et al.  The enhancement of virus infectivity by antibody , 1967 .

[22]  R. Hawkes,et al.  ENHANCEMENT OF THE INFECTIVITY OF ARBOVIRUSES BY SPECIFIC ANTISERA PRODUCED IN DOMESTIC FOWLS. , 1964, The Australian journal of experimental biology and medical science.

[23]  N. Karabatsos,et al.  Antigenic relationships between flaviviruses as determined by cross-neutralization tests with polyclonal antisera. , 1989, The Journal of general virology.

[24]  S. Halstead,et al.  Immune enhancement of viral infection. , 1982, Progress in allergy.