A treatment for and vaccine against the deadly Hendra and Nipah viruses

Abstract

Hendra virus and Nipah virus are bat-borne paramyxoviruses that are the prototypic members of the genus Henipavirus. The henipaviruses emerged in the 1990s, spilling over from their natural bat hosts and causing serious disease outbreaks in humans and livestock. Hendra virus emerged in Australia and since 1994 there have been 7 human infections with 4 case fatalities. Nipah virus first appeared in Malaysia and subsequent outbreaks have occurred in Bangladesh and India. In total, there have been an estimated 582 human cases of Nipah virus and of these, 54% were fatal. Their broad species tropism and ability to cause fatal respiratory and/or neurologic disease in humans and animals make them important transboundary biological threats. Recent experimental findings in animals have demonstrated that a human monoclonal antibody targeting the viral G glycoprotein is an effective post-exposure treatment against Hendra and Nipah virus infection. In addition, a subunit vaccine based on the G glycoprotein of Hendra virus affords protection against Hendra and Nipah virus challenge. The vaccine has been developed for use in horses in Australia and is the first vaccine against a Biosafety Level-4 (BSL-4) agent to be licensed and commercially deployed. Together, these advances offer viable approaches to address Hendra and Nipah virus infection of livestock and people.

Keywords: G glycoprotein; Hendra virus; Horse; Monoclonal antibody; Nipah virus; Vaccine.

Figure 1

Model of the Hendra virus soluble G glycoprotein subunit vaccine (HeV-sG) and its complex with the henipavirus-neutralizing human monoclonal antibody m102. A: The HeV-sG glycoprotein subunit vaccine is composed of the entire ectodomain (amino acids 76-604) of the HeV G glycoprotein. Here, HeV-sG is shown as dimer with one monomer colored green and the other cyan. The secondary structure elements of the two globular head domains are derived from the crystal structure of the HeV G head domain (Colgrave et al., 2011; Xu et al., 2012b), and the stalk regions of each G monomer (residues 77-136) are modeled (Kelley and Sternberg, 2009). N-linked glycosylation sites shown as gray spheres. The ephrin-binding face of the cyan globular head is facing forward with an overlay of the interacting ephrin-B2 G-H loop residues in yellow. B: The HeV-sG dimer shown in complex with two m102.3 Fab antibody fragments. The two HeV-sG monomers are colored green and cyan as in panel A and rotated slightly to the right. The two Fab m102.3 molecules are shown with their heavy chains colored in magenta and light chain in yellow, each binding one globular head domains of G. (Xu, K. et al., submitted).