A Hendra Virus G Glycoprotein Subunit Vaccine Protects African Green Monkeys from Nipah Virus Challenge

Abstract

In the 1990s, Hendra virus and Nipah virus (NiV), two closely related and previously unrecognized paramyxoviruses that cause severe disease and death in humans and a variety of animals, were discovered in Australia and Malaysia, respectively. Outbreaks of disease have occurred nearly every year since NiV was first discovered, with case fatality ranging from 10 to 100%. In the African green monkey (AGM), NiV causes a severe lethal respiratory and/or neurological disease that essentially mirrors fatal human disease. Thus, the AGM represents a reliable disease model for vaccine and therapeutic efficacy testing. We show that vaccination of AGMs with a recombinant subunit vaccine based on the henipavirus attachment G glycoprotein affords complete protection against subsequent NiV infection with no evidence of clinical disease, virus replication, or pathology observed in any challenged subjects. Success of the recombinant subunit vaccine in nonhuman primates provides crucial data in supporting its further preclinical development for potential human use.

Altered Immunogenicity of Donor Lungs via Removal of Passenger Leukocytes Using Ex Vivo Lung Perfusion

“…Histological preparation of lung tissue: Lung tissue biopsies, one central and two peripheral from each lobe, were fixed in 10% buffered formalin solution and paraffin-embedded (13). Four-micron sections were cut, deparaffinized, and stained with hematoxylin, eosin, and saffron.…”

A Recombinant Hendra Virus G Glycoprotein Subunit Vaccine Protects Nonhuman Primates against Hendra Virus Challenge

“…Production and purification of sG HeV were done as previously described (26). Two vaccines containing sG HeV and Alhydrogel (Accurate Chemical & Scientific Corporation, Westbury, NY) at a weight ratio of 1:25 were prepared with one formulation also containing CpG oligodeoxynucleotide (ODN) 2006 (InvivoGen, San Diego, CA) with a fully phosphorothioate-modified backbone (sG HeV -alum-CpG).…”

“…A recombinant adeno-associated virus vaccine expressing the NiV G protein completely protected hamsters against a homologous NiV challenge and protected 50% of the animals against a heterologous HeV infection (21). In addition, a recombinant subunit vaccine based on the HeV G protein (sG HeV ) completely protected small animals against lethal HeV and NiV infections (22)(23)(24)(25) and more recently was shown to be efficacious in the robust AGM model of NiV infection (26). sG HeV (amino acids 73 to 604) is an engineered secreted version of the full ectodomain of the G glycoprotein in which the transmembrane and cytoplasmic tail domains have been deleted from the N terminus (27).…”

Henipavirus Pathogenesis in Human Respiratory Epithelial Cells

“…Although the exact route of infection in humans is unknown, previous studies in several laboratory animal models reported an efficient infection through intranasal challenge (31)(32)(33)(34)(35), suggesting that the respiratory tract is one of the first targets of virus replication. In addition, both NiV and HeV have been isolated from oropharyngeal and respiratory secretions from humans and animals (36)(37)(38), which emphasizes the importance of the respiratory tract in virus replication and potential transmission.…”