ORCID Profile
0000-0002-4619-3667
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Publisher: Elsevier BV
Date: 12-2020
Publisher: MDPI AG
Date: 19-02-2014
DOI: 10.3390/V6020909
Publisher: Cold Spring Harbor Laboratory
Date: 18-02-2021
DOI: 10.1101/2021.02.17.431743
Abstract: Hendra virus (HeV) and Nipah virus (NiV), the prototypic members of the Henipavirus (HNV) genus, are emerging, zoonotic paramyxoviruses known to cause severe disease across six mammalian orders, including humans (Eaton et al., 2006). While several research groups have made strides in developing candidate vaccines and therapeutics against henipaviruses, such countermeasures have not been licensed for human use, and significant gaps in knowledge about the human immune response to these viruses exist. To address these gaps, we isolated a large panel of human monoclonal antibodies (mAbs) from the B cells of an in idual with prior occupation-related exposure to the equine HeV vaccine (Equivac® HeV). Competition-binding and hydrogen-deuterium exchange mass spectrometry (HDX-MS) studies identified at least six distinct antigenic sites on the HeV/NiV receptor binding protein (RBP) that are recognized by human mAbs. Antibodies recognizing multiple antigenic sites potently neutralized NiV and/or HeV isolates in vitro. The most potent class of cross-reactive antibodies achieved neutralization by blocking viral attachment to the host cell receptors ephrin-B2 and ephrin-B3. Antibodies from this class mimic receptor binding by inducing a receptor-bound conformation to the HeV-RBP protein tetramer, exposing an epitope that appears to lie hidden in the interface between protomers within the HeV-RBP tetramer. Antibodies that recognize this cryptic epitope potently neutralized HeV and NiV. Flow cytometric studies using cell-surface-displayed HeV-RBP protein showed that cross-reactive, neutralizing mAbs from each of these classes cooperate for binding. In a highly stringent hamster model of NiV B infection, antibodies from both classes reduced morbidity and mortality and achieved synergistic protection in combination and provided therapeutic benefit when combined into two bispecific platforms. These studies identified multiple candidate mAbs that might be suitable for use in a cocktail therapeutic approach to achieve synergistic antiviral potency and reduce the risk of virus escape during treatment.
Publisher: Proceedings of the National Academy of Sciences
Date: 26-05-2022
Abstract: A new Hendra virus variant (HeV-g2) has been recently identified in two independent studies, increasing the concern of HeV spillover. Here, we show that HeV-g2 utilizes the same host receptor as HeV and that a panel of previously described HeV neutralizing antibodies cross-neutralizes HeV-g2 potently. Furthermore, we describe a monoclonal antibody (hAH1.3) neutralizing HeV and HeV-g2 and reveal its epitope using X-ray crystallography. We show that targeting four nonoverlapping epitopes on the HeV attachment protein simultaneously leads to potent HeV and HeV-g2 neutralization, supporting the development of a tetravalent monoclonal antibody cocktail. Collectively, our data provide a comprehensive assessment of available countermeasures against this newly described HeV-g2 variant and delineate multiple strategies for pandemic preparedness.
Publisher: Public Library of Science (PLoS)
Date: 31-12-2018
Publisher: Wiley
Date: 04-02-2018
DOI: 10.1111/AVJ.12679
Abstract: To evaluate the effect of Equivac® HeV Hendra virus vaccine on Thoroughbred racing performance. Retrospective pre-post intervention study. Thoroughbreds with at least one start at one of six major south-eastern Queensland race tracks between 1 July 2012 and 31 December 2016 and with starts in the 3-month periods before and after Hendra virus vaccinations were identified. Piecewise linear mixed models compared the trends in 'Timeform rating' and 'margin to winner' before and after initial Hendra virus vaccination. Generalised linear mixed models similarly compared the odds of 'winning', 'placing' (1st-3rd) and 'winning any prize money'. Timeform rating trends were also compared before and after the second and subsequent vaccinations. Analysis of data from 4208 race starts by 755 horses revealed no significant difference in performance in the 3 months before versus 3 months after initial Hendra vaccination for Timeform rating (P = 0.32), 'Margin to winner' (P = 0.45), prize money won (P = 0.25), wins (P = 0.64) or placings (P = 0.77). Further analysis for Timeform rating for 7844 race starts by 928 horses failed to identify any significant change in Timeform rating trends before versus after the second and subsequent vaccinations (P = 0.16) or any evidence of a cumulative effect for the number of vaccines received (P = 0.22). No evidence of an effect of Hendra virus vaccination on racing performance was found. The findings allow owners, trainers, industry regulators and animal health authorities to make informed decisions about vaccination.
Publisher: Hindawi Limited
Date: 19-07-2020
DOI: 10.1111/TBED.13673
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1016/J.VETMIC.2014.07.029
Abstract: In May 2013, the first cases of Australian bat lyssavirus infections in domestic animals were identified in Australia. Two horses (filly-H1 and gelding-H2) were infected with the Yellow-bellied sheathtail bat (YBST) variant of Australian bat lyssavirus (ABLV). The horses presented with neurological signs, pyrexia and progressing ataxia. Intra-cytoplasmic inclusion bodies (Negri bodies) were detected in some Purkinje neurons in haematoxylin and eosin (H&E) stained sections from the brain of one of the two infected horses (H2) by histological examination. A morphological diagnosis of sub-acute moderate non-suppurative, predominantly angiocentric, meningo-encephalomyelitis of viral aetiology was made. The presumptive diagnosis of ABLV infection was confirmed by the positive testing of the affected brain tissue from (H2) in a range of laboratory tests including fluorescent antibody test (FAT) and real-time PCR targeting the nucleocapsid (N) gene. Retrospective testing of the oral swab from (H1) in the real-time PCR also returned a positive result. The FAT and immunohistochemistry (IHC) revealed an abundance of ABLV antigen throughout the examined brain sections. ABLV was isolated from the brain (H2) and oral swab/saliva (H1) in the neuroblastoma cell line (MNA). Alignment of the genome sequence revealed a 97.7% identity with the YBST ABLV strain.
Publisher: Wiley
Date: 11-06-2020
DOI: 10.1111/AVJ.12957
Publisher: Wiley
Date: 24-08-2014
DOI: 10.1111/AVJ.12227
Abstract: The first two confirmed cases of Australian bat lyssavirus (ABLV) infection in horses are presented. Both cases occurred in the same week in May 2013 in paddock mates in south-east Queensland. Australia has been one of only a few countries considered free from rabies-like viruses in domestic animal species. ABLV infection had previously only been confirmed in bats and humans. All three confirmed human cases were fatal, the latest in February 2013. An additional human case of possible abortive infection in 1996 has also been reported. Both equine cases reported here resulted in euthanasia. The risks of infection across other mammalian species are still to be determined. These two equine cases highlight that ABLV should be considered as a differential diagnosis in animals with similar clinical presentations in Australia. There is a need for greater awareness regarding the zoonotic risk, use of personal protective equipment, pre- and post-exposure prophylactic measures and laboratory diagnostic options. The authors recommend ABLV testing for all Australian cases of progressive equine neurological disease.
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 03-2022
Publisher: Cold Spring Harbor Laboratory
Date: 17-07-2021
DOI: 10.1101/2021.07.16.452724
Abstract: A novel Hendra virus (HeV) variant, not detected by routine testing, was identified and isolated from a Queensland horse that suffered acute, fatal disease consistent with HeV infection. Whole genome sequencing and phylogenetic analysis demonstrated the variant to have ~83% nucleotide identity to the prototype HeV strain. An updated RT-qPCR assay was designed for routine HeV surveillance. In silico and in vitro comparison of the receptor-binding protein with prototypic HeV showed that the human monoclonal antibody m102.4 used for post-exposure prophylaxis, as well as the current equine vaccine, should be effective against this variant. Genetic similarity of this virus to sequences detected from grey-headed flying-foxes suggests the variant circulates at-least in this species. Studies determining infection kinetics, pathogenicity, reservoir-species associations, viral–host co-evolution and spillover dynamics for this virus are urgently needed. Surveillance and biosecurity practices should be updated to appreciate HeV spillover risk across all regions frequented by flying foxes.
Publisher: Elsevier BV
Date: 12-2022
Publisher: Elsevier BV
Date: 12-2020
Publisher: Elsevier BV
Date: 12-2020
Publisher: Elsevier BV
Date: 12-2020
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 05-2022
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: Australia
No related grants have been discovered for Edward J Annand.