Live chimeric and inactivated Japanese encephalitis virus vaccines differ in their cross-protective values against Murray Valley encephalitis virus.
The Japanese encephalitis virus (JEV) serocomplex, which also includes Murray Valley encephalitis virus (MVEV), is a group of antigenically closely related, mosquito-borne flaviviruses that are responsible for severe encephalitic disease in humans. While vaccines against the prominent members of this serocomplex are available or under development, it is unlikely that they will be produced specifically against those viruses which cause less-frequent disease, such as MVEV. Here we have evaluated the cross-protective values of an inactivated JEV vaccine (JE-VAX) and a live chimeric JEV vaccine (ChimeriVax-JE) against MVEV in two mouse models of flaviviral encephalitis. We show that (i) a three-dose vaccination schedule with JE-VAX provides cross-protective immunity, albeit only partial in the more severe challenge model; (ii) a single dose of ChimeriVax-JE gives complete protection in both challenge models; (iii) the cross-protective immunity elicited with ChimeriVax-JE is durable (>or=5 months) and broad (also giving protection against West Nile virus); (iv) humoral and cellular immunities elicited with ChimeriVax-JE contribute to protection against lethal challenge with MVEV; (v) ChimeriVax-JE remains fully attenuated in immunodeficient mice lacking type I and type II interferon responses; and (vi) immunization with JE-VAX, but not ChimeriVax-JE, can prime heterologous infection enhancement in recipients of vaccination on a low-dose schedule, designed to mimic vaccine failure or waning of vaccine-induced immunity. Our results suggest that the live chimeric JEV vaccine will protect against other viruses belonging to the JEV serocomplex, consistent with the observation of cross-protection following live virus infections.
Lobigs
Mario
M
Division of Immunology and Genetics, John Curtin School of Medical Research, The Australian National University, P.O. Box 334, Canberra, A.C.T. 2601, Australia. Mario.Lobigs@anu.edu.au
Larena
Maximilian
M
Alsharifi
Mohammed
M
Lee
Eva
E
Pavy
Megan
M
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D003429:Cross Reactions; D004664:Encephalitis Virus, Japanese / Q000276:immunology*; D018068:Encephalitis Virus, Murray Valley / Q000276:immunology*; D004671:Encephalitis, Arbovirus / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007117:Immunization, Secondary; D007156:Immunologic Memory; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016019:Survival Analysis; D013997:Time Factors; D014613:Vaccines, Attenuated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic