Safety and immunogenicity of a delta inulin-adjuvanted inactivated Japanese encephalitis virus vaccine in pregnant mares and foals.

Helle Bielefeldt-Ohmann,Nikolai Petrovsky,Cindy Se Tan,Lisa Kidd,Mitchell Coyle,Alysha Douma,Roy A Hall,Natalie A Prow,Jody Hobson-Peters,Wenqi Wang

doi:10.1186/s13567-014-0130-7

Abstract

In 2011, following severe flooding in Eastern Australia, an unprecedented epidemic of equine encephalitis occurred in South-Eastern Australia, caused by Murray Valley encephalitis virus (MVEV) and a new variant strain of Kunjin virus, a subtype of West Nile virus (WNVKUN). This prompted us to assess whether a delta inulin-adjuvanted, inactivated cell culture-derived Japanese encephalitis virus (JEV) vaccine (JE-ADVAX™) could be used in horses, including pregnant mares and foals, to not only induce immunity to JEV, but also elicit cross-protective antibodies against MVEV and WNVKUN. Foals, 74–152 days old, received two injections of JE-ADVAX™. The vaccine was safe and well-tolerated and induced a strong JEV-neutralizing antibody response in all foals. MVEV and WNVKUN antibody cross-reactivity was seen in 33% and 42% of the immunized foals, respectively. JE-ADVAX™ was also safe and well-tolerated in pregnant mares and induced high JEV-neutralizing titers. The neutralizing activity was passively transferred to their foals via colostrum. Foals that acquired passive immunity to JEV via maternal antibodies then were immunized with JE-ADVAX™ at 36–83 days of age, showed evidence of maternal antibody interference with low peak antibody titers post-immunization when compared to immunized foals of JEV-naïve dams. Nevertheless, when given a single JE-ADVAX™ booster immunization as yearlings, these animals developed a rapid and robust JEV-neutralizing antibody response, indicating that they were successfully primed to JEV when immunized as foals, despite the presence of maternal antibodies. Overall, JE-ADVAX™ appears safe and well-tolerated in pregnant mares and young foals and induces protective levels of JEV neutralizing antibodies with partial cross-neutralization of MVEV and WNVKUN.

Highlights

Flaviviruses of the Japanese encephalitis virus (JEV) serocomplex are amongst the most important encephalitic viruses worldwide, affecting humans, wild birds, and several mammalian species, including domestic animal species such as horses
JE-ADVAXTM responses in foals born to naïve mares In this trial, 19 foals, aged 74–152 days and born to non-vaccinated, flavivirus sero-negative mares, were enrolled
The results of this study corroborate and extend those of a previous study by Lobigs et al [13] and show that the cell culture-derived, inactivated JE-vaccine is safe in horses of any age and when delivered with the novel polysaccharide adjuvant Advax elicits a strong JEV-specific neutralizing antibody response in both pregnant adult horses and in very young foals which lasts at least 10–11 months in the majority of the animals (Tables 1 and 2)

Summary

Introduction

Flaviviruses of the Japanese encephalitis virus (JEV) serocomplex are amongst the most important encephalitic viruses worldwide, affecting humans, wild birds, and several mammalian species, including domestic animal species such as horses. An inactivated JEV vaccine, developed in Japan in the 1960s (JE-VAX), dramatically reduced the number of human and equine cases of JE in that country [10]. This vaccine ceased to be manufactured in 2005, due to perceived safety problems and excessive reactogenicity, with subsequent JEV vaccines being developed based on inactivated virus grown in cell culture [10,11]. Vaccine failure and fatal encephalitis due to naturally acquired JEV infection has been reported in a racing horse imported from Australia into Hong Kong [5]. Cases of equine JE have the potential to cause significant adverse economic effect on the horse industry, which is estimated to contribute greater than $6 billion to the GDP in Australia alone [12]

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