A recombinant Hendra virus G glycoprotein-based subunit vaccine protects ferrets from lethal Hendra virus challenge

The henipaviruses, Hendra virus (Hey) and Nipah virus (NiV), are two deadly zoonotic viruses for which no vaccines or therapeutics have yet been approved for human or livestock use. In 14 outbreaks since 1994 Hey has been responsible for multiple fatalities in horses and humans, with all known human infections resulting from close contact with infected horses. A vaccine that prevents virus shedding in infected horses could interrupt the chain of transmission to humans and therefore prevent Hey disease in both. Here we characterise HeV infection in a ferret model and show that it closely mirrors the disease seen in humans and horses with induction of systemic vasculitis, including involvement of the pulmonary and central nervous systems. This model of Hey infection in the ferret was used to assess the immunogenicity and protective efficacy of a subunit vaccine based on a recombinant soluble version of the HeV attachment glycoprotein G (HeVsG), adjuvanted with CpG. We report that ferrets vaccinated with a 100 mu g, 20 mu g or 4 mu g dose of HeVsG remained free of clinical signs of Hey infection following a challenge with 5000 TCID50 of HeV. In addition, and of considerable importance, no evidence of virus or viral genome was detected in any tissues or body fluids in any ferret in the 100 and 20 mu g groups, while genome was detected in the nasal washes only of one animal in the 414 group. Together, our findings indicate that 100 mu g or 20 mu g doses of HeVsG vaccine can completely prevent a productive Hey infection in the ferret, suggesting that vaccination to prevent the infection and shedding of Hey is possible. (C) 2011 Elsevier Ltd. All rights reserved.