![]() Members of this large panel of antibodies target diverse antigenic sites, many of which are sites of vulnerability for neutralization for at least one virus. In this study, we isolated hmAbs from circulating B cells of an individual with occupation-related exposure to the equine HeV vaccine (Equivac HeV), the same individual from whom therapeutic mAbs HENV-26 and HENV-32 were previously isolated ( Dong et al., 2020 Middleton et al., 2014). While these studies have laid a foundation for our understanding of how to target henipaviruses therapeutically, many questions remain regarding the antigenicity of the attachment glycoprotein, and whether escape mutations from these mAbs can develop in vivo. More recently, two human mAbs, HENV-26 and HENV-32, were shown to neutralize HeV and NiV by distinct mechanisms and protect from NiV Bangladesh (NiV B) strain challenge in a ferret model ( Dong et al., 2020). This mAb potently neutralizes both HeV and NiV in vitro and protects against infection and disease in experimental henipavirus challenge models using ferrets or non-human primates ( Bossart et al., 2011 Geisbert et al., 2014 Mire et al., 2016). One of these studies used phage display technology to isolate a human monoclonal antibody (hmAb), designated m102.4 ( Zhu et al., 2008). These data have been corroborated in multiple studies by investigators using murine, rabbit, or human antibody discovery technologies to isolate potently neutralizing antibodies to HeV and/or NiV ( Aguilar et al., 2009 Mire et al., 2020 Zhu et al., 2006). Passive immune transfer studies in both hamsters and ferrets have provided evidence that neutralizing antibodies are a correlate of immunoprotection from henipaviruses ( Bossart et al., 2009 Guillaume et al., 2004, 2006). The risk of a global health crisis associated with henipaviruses is exacerbated by the lack of licensed antiviral drugs or vaccines for Henipavirus (HNV) and a dearth of knowledge of the human immune response to these viruses ( Escaffre et al., 2013 Gómez Román et al., 2020). Such consideration prompted the World Health Organization (WHO) to designate henipavirus infections as priority diseases requiring extensive and immediate research and development ( Sweileh, 2017). While HeV and NiV outbreaks historically have been confined geographically to Australia and Southeast Asia, respectively, the risk of pandemic spread of these highly pathogenic agents related to regional and global population densities and the difficulty of avoiding international transmission via infected travelers have been highlighted by recent experience with SARS-CoV-2 ( Morens and Fauci, 2020). ![]() These factors together with their resultant increase in intermediate host contact (humans and domestic animals) are associated with increasing geographic range and frequency of henipavirus disease spillover ( Martin et al., 2018 Walsh et al., 2017). ![]() Anthropogenic and climatic influences on flying foxes are affecting their roosting, feeding, and migration habits as well as their susceptibility to heat-stress, disease, and injury ( Kessler et al., 2018 Plowright et al., 2015). ![]() More direct routes of infection, including human-to-human transmission, and mortality rates approaching 100% have been observed during recent NiV outbreaks ( Chadha et al., 2006 Clayton et al., 2012 Gurley et al., 2007). ![]() NiV, which was discovered 4 years after HeV when hundreds of pig handlers fell ill with encephalitic disease ( Chua et al., 1999), has continued to cause sporadic outbreaks in Bangladesh and India ( Arunkumar et al., 2019 Soman Pillai et al., 2020). Spillover has occurred sporadically with some seasonal and climatic trends since then, causing disease in 105 horses and 7 humans, with high case fatality rates ( Queensland Government, 2020). HeV was identified in 1994, having caused the death of 14 of 21 infected horses and 1 of 2 infected humans in Queensland, Australia ( Murray et al., 1995b Selvey et al., 1995). HeV is transmitted from flying foxes to horses and from horses to in-contact humans, causing severe respiratory and/or encephalitic disease mediated by endothelial vasculitis in both ( Escaffre et al., 2013 Field, 2016 Murray et al., 1995a). Multiple species of pteropid bats (flying foxes) act as reservoir hosts for these negative-sense, single-stranded RNA viruses in the Paramyxoviridae family with which they are understood to have co-evolved ( Chua et al., 2002 Halpin et al., 2011 Halpin et al., 2000 Vidgen et al., 2015). Hendra virus (HeV) ( Guirakhoo et al., 2002) and Nipah virus (NiV), the prototypic henipaviruses, are emerging zoonotic paramyxoviruses known to cause severe disease in humans and diverse other mammalian orders. ![]()
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