Protection from Hendra virus infection with Canarypox recombinant vaccine.

Vanessa Guillaume-Vasselin,Catherine Charreyre,Branka Horvat,Kévin P Dhondt,Amelie Poulard,Laurent Lemaitre,Laurence Tedeschi

doi:10.1038/npjvaccines.2016.3

Abstract

Hendra virus (HeV) is an emerging zoonotic pathogen, which causes severe respiratory illness and encephalitis in humans and horses. Since its first appearance in 1994, spillovers of HeV from its natural reservoir fruit bats occur on almost an annual basis. The high mortality rate in both humans and horses and the wide-ranging reservoir distribution are making HeV a serious public health problem, especially for people exposed to sick horses. This study has aimed to develop an efficient low-cost HeV vaccine for horses based on Canarypox recombinant vector expressing HeV glycoproteins, attachment glycoprotein (G) and fusion protein (F). This vaccine was used to immunise hamsters and then challenged intraperitoneally with HeV 3 weeks later. The higher tested dose of the vaccine efficiently prevented oropharyngeal virus shedding and protected animals from clinical disease and virus-induced mortality. Vaccine induced generation of seroneutralising antibodies and prevented virus-induced histopathological changes and a production of viral RNA and antigens in animal tissues. Interestingly, some vaccinated animals, including those immunised at a lower dose, were protected in the absence of detectable specific antibodies, suggesting the induction of an efficient virus-specific cellular immunity. Finally, ponies immunised using the same vaccination protocol as hamsters developed strong seroneutralising titres against both HeV and closely related Nipah virus, indicating that this vaccine may have the ability to induce cross-protection against Henipavirus infection. These data suggest that Canarypox-based vectors encoding for HeV glycoproteins present very promising new vaccine candidate to prevent infection and shedding of the highly lethal HeV.

Highlights

Hendra virus (HeV) along with the closely related Nipah virus (NiV)is a highly pathogenic Henipavirus of the Paramyxoviridae family
Expression of HeV glycoproteins G and F by Canarypox-based vaccines five out of eight hamsters (63%) vaccinated with the low dose were protected from clinical disease (Figure 2b)
Wide distribution of the Henipavirus natural host raises the risk of potential pandaemics caused by this virus in the future[22] and urges the better understanding of its pathogenesis and the development of efficient antiviral approaches.[23]

Summary

Introduction

Hendra virus (HeV) along with the closely related Nipah virus (NiV)is a highly pathogenic Henipavirus of the Paramyxoviridae family. While HeV appeared in 1994 in Australia in horses and humans,[1] NiV was first identified in 1998 in Malaysia in pigs and humans.[2] Both are zoonotic viruses and are able to infect a wide range of mammalian species including pigs, horses, cattle, cats and dogs.[3] Since their first appearance, numerous outbreaks of both viruses have occurred with evidence of human-to-human transmission and a mortality rate that can approach 75% for NiV.[4] Between. Flying foxes of the genus Pteropus are considered to be the natural reservoir for Henipaviruses, and their geographic distribution includes all regions where HeV and NiV outbreaks have occurred. Transmission and spillover infection is thought to occur through food contaminations or direct contact with secretions from infected animals.[6,7] Horses become infected when the HeV spills over from Pteropus flying foxes and infection could be transmitted to humans following the exposure to the secretions of infected horses. HeV has low infectivity in horses and humans but a high mortality rate in both species (75% and 57% respectively).[8]

Objectives

Methods

Findings

Conclusion