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1.
Vet Microbiol ; 295: 110167, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38954881

RESUMO

Hendra virus (HeV) is lethal to horses and a zoonotic threat to humans in Australia, causing severe neurological and/or respiratory disease with high mortality. An equine vaccine has been available since 2012. Foals acquire antibodies from their dams by ingesting colostrum after parturition, therefore it is assumed that foals of mares vaccinated against HeV will have passive HeV antibodies circulating during the first several months of life until they are actively vaccinated. However, no studies have yet examined passive or active immunity against HeV in foals. Here, we investigated anti-HeV antibody levels in vaccinated mares and their foals. Testing for HeV neutralising antibodies is cumbersome due to the requirement for Biosafety level 4 (BSL-4) containment to conduct virus neutralisation tests (VNT). For this study, a subset of samples was tested for HeV G-specific antibodies by both an authentic VNT with infectious HeV and a microsphere-based immunoassay (MIA), revealing a strong correlation. An indicative neutralising level was then applied to the results of a larger sample set tested using the MIA. Mares had high levels of HeV-specific neutralising antibodies at the time of parturition. Foals acquired high levels of maternal antibodies which then waned to below predictive protective levels in most foals by 6 months old when vaccination commenced. Foals showed a suboptimal response to vaccination, suggesting maternal antibodies may interfere with active vaccination. The correlation analysis between the authentic HeV VNT and HeV MIA will enable further high throughput serological studies to inform optimal vaccination protocols for both broodmares and foals.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vírus Hendra , Infecções por Henipavirus , Doenças dos Cavalos , Vacinação , Vacinas Virais , Animais , Cavalos , Vírus Hendra/imunologia , Doenças dos Cavalos/prevenção & controle , Doenças dos Cavalos/virologia , Doenças dos Cavalos/imunologia , Anticorpos Antivirais/sangue , Infecções por Henipavirus/prevenção & controle , Infecções por Henipavirus/veterinária , Infecções por Henipavirus/imunologia , Infecções por Henipavirus/virologia , Feminino , Vacinação/veterinária , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Anticorpos Neutralizantes/sangue , Imunidade Materno-Adquirida , Animais Recém-Nascidos/imunologia , Gravidez , Testes de Neutralização/veterinária , Austrália , Colostro/imunologia
2.
Viruses ; 16(5)2024 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-38793674

RESUMO

The Nipah virus (NiV) and the Hendra virus (HeV) are highly pathogenic zoonotic diseases that can cause fatal infections in humans and animals. Early detection is critical for the control of NiV and HeV infections. We present the development of two antigen-detection ELISAs (AgELISAs) using the henipavirus-receptor EphrinB2 and monoclonal antibodies (mAbs) to detect NiV and HeV. The NiV AgELISA detected only NiV, whereas the NiV/HeV AgELISA detected both NiV and HeV. The diagnostic specificities of the NiV AgELISA and the NiV/HeV AgELISA were 100% and 97.8%, respectively. Both assays were specific for henipaviruses and showed no cross-reactivity with other viruses. The AgELISAs detected NiV antigen in experimental pig nasal wash samples taken at 4 days post-infection. With the combination of both AgELISAs, NiV can be differentiated from HeV. Complementing other henipavirus detection methods, these two newly developed AgELISAs can rapidly detect NiV and HeV in a large number of samples and are suitable for use in remote areas where other tests are not available.


Assuntos
Anticorpos Monoclonais , Anticorpos Antivirais , Ensaio de Imunoadsorção Enzimática , Efrina-B2 , Vírus Hendra , Infecções por Henipavirus , Vírus Nipah , Vírus Hendra/imunologia , Animais , Vírus Nipah/imunologia , Anticorpos Monoclonais/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Efrina-B2/metabolismo , Efrina-B2/imunologia , Infecções por Henipavirus/diagnóstico , Infecções por Henipavirus/virologia , Infecções por Henipavirus/imunologia , Anticorpos Antivirais/imunologia , Suínos , Humanos , Sensibilidade e Especificidade , Receptores Virais/metabolismo , Antígenos Virais/imunologia
3.
Nat Commun ; 15(1): 4330, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773072

RESUMO

The Hendra and Nipah viruses (HNVs) are highly pathogenic pathogens without approved interventions for human use. In addition, the interaction pattern between the attachment (G) and fusion (F) glycoproteins required for virus entry remains unclear. Here, we isolate a panel of Macaca-derived G-specific antibodies that cross-neutralize HNVs via multiple mechanisms. The most potent antibody, 1E5, confers adequate protection against the Nipah virus challenge in female hamsters. Crystallography demonstrates that 1E5 has a highly similar binding pattern to the receptor. In cryo-electron microscopy studies, the tendency of 1E5 to bind to the upper or lower heads results in two distinct quaternary structures of G. Furthermore, we identify the extended outer loop ß1S2-ß1S3 of G and two pockets on the apical region of fusion (F) glycoprotein as the essential sites for G-F interactions. This work highlights promising drug candidates against HNVs and contributes deeper insights into the viruses.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Microscopia Crioeletrônica , Infecções por Henipavirus , Proteínas Virais de Fusão , Animais , Anticorpos Neutralizantes/imunologia , Feminino , Anticorpos Antivirais/imunologia , Infecções por Henipavirus/virologia , Infecções por Henipavirus/imunologia , Proteínas Virais de Fusão/imunologia , Proteínas Virais de Fusão/química , Humanos , Proteínas do Envelope Viral/imunologia , Proteínas do Envelope Viral/química , Vírus Nipah/imunologia , Internalização do Vírus/efeitos dos fármacos , Henipavirus/imunologia , Cricetinae , Reações Cruzadas/imunologia , Vírus Hendra/imunologia , Macaca , Mesocricetus , Cristalografia por Raios X
4.
Trop Med Int Health ; 29(5): 354-364, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38415314

RESUMO

OBJECTIVES: Nipah and Hendra are deadly zoonotic diseases with pandemic potential. To date, no human vaccine or monoclonal antibody (mAb) has been licensed to prevent disease caused by these pathogens. The aim of this scoping review was to identify and describe all Phase I, II, and III clinical trials of vaccine candidates or mAbs candidates designed to prevent Nipah and Hendra in humans and to compare the characteristics of the vaccine candidates to characteristics outlined in the Target Product Profile drafted by the World Health Organisation as part of the WHO Research & Development Blueprint for Action to Prevent Epidemics. METHODS: We searched 23 clinical trial registries, the Cochrane Central Register of Clinical Trials, and grey literature up to June 2023 to identify vaccine and mAb candidates being evaluated in registered clinical trials. Vaccine candidate and trial characteristics were double-extracted for evaluation and the vaccine candidate characteristics were compared with the preferred and critical criteria of the World Health Organisation's Target Product Profile for Nipah virus vaccine. RESULTS: Three vaccine candidates (Hendra Virus Soluble Glycoprotein Vaccine [HeV-sG-V], PHV02, and mRNA-1215) and one mAb (m102.4) had a registered human clinical trial by June 2023. All trials were phase 1, dose-ranging trials taking place in the United States of America or Australia and enrolling healthy adults. Although all vaccine candidates meet the dose regimen and route of administration criteria of the Target Product Profile, other criteria such as measures of efficacy and reactogenicity will need to be evaluated in the future as evidence becomes available. CONCLUSION: Multiple vaccine candidates and one mAb candidate have reached the stage of human clinical trials and are reviewed here. Monitoring progress during evaluation of these candidates and candidates entering clinical trials in the future can help highlight many of the challenges that remain.


Assuntos
Anticorpos Monoclonais , Vírus Hendra , Infecções por Henipavirus , Vírus Nipah , Vacinas Virais , Humanos , Infecções por Henipavirus/prevenção & controle , Infecções por Henipavirus/imunologia , Anticorpos Monoclonais/uso terapêutico , Vírus Hendra/imunologia , Vírus Nipah/imunologia , Vacinas Virais/imunologia , Vacinas Virais/uso terapêutico , Ensaios Clínicos como Assunto , Animais
5.
Proc Natl Acad Sci U S A ; 119(22): e2122769119, 2022 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-35617431

RESUMO

Hendra virus (HeV) and Nipah virus (NiV) are deadly zoonotic Henipaviruses (HNVs) responsible for recurrent outbreaks in humans and domestic species of highly fatal (50 to 95%) disease. A HeV variant (HeV-g2) of unprecedented genetic divergence has been identified in two fatally diseased horses, and in two flying fox species in regions of Australia not previously considered at risk for HeV spillover. Given the HeV-g2 divergence from HeV while retaining equivalent pathogenicity and spillover potential, understanding receptor usage and antigenic properties is urgently required to guide One Health biosecurity. Here, we show that the HeV-g2 G glycoprotein shares a conserved receptor tropism with prototypic HeV and that a panel of monoclonal antibodies recognizing the G and F glycoproteins potently neutralizes HeV-g2­ and HeV G/F­mediated entry into cells. We determined a crystal structure of the Fab fragment of the hAH1.3 antibody bound to the HeV G head domain, revealing an antigenic site associated with potent cross-neutralization of both HeV-g2 and HeV. Structure-guided formulation of a tetravalent monoclonal antibody (mAb) mixture, targeting four distinct G head antigenic sites, results in potent neutralization of HeV and HeV-g2 and delineates a path forward for implementing multivalent mAb combinations for postexposure treatment of HNV infections.


Assuntos
Anticorpos Monoclonais , Anticorpos Neutralizantes , Anticorpos Antivirais , Vírus Hendra , Fragmentos Fab das Imunoglobulinas , Proteínas do Envelope Viral , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/química , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/química , Anticorpos Antivirais/imunologia , Cristalografia por Raios X , Epitopos/química , Epitopos/genética , Vírus Hendra/genética , Vírus Hendra/imunologia , Humanos , Fragmentos Fab das Imunoglobulinas/química , Testes de Neutralização , Profilaxia Pós-Exposição , Domínios Proteicos , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia
6.
Nat Struct Mol Biol ; 28(5): 426-434, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33927387

RESUMO

Hendra virus (HeV) and Nipah virus (NiV) are henipaviruses (HNVs) causing respiratory illness and severe encephalitis in humans, with fatality rates of 50-100%. There are no licensed therapeutics or vaccines to protect humans. HeV and NiV use a receptor-binding glycoprotein (G) and a fusion glycoprotein (F) to enter host cells. HNV F and G are the main targets of the humoral immune response, and the presence of neutralizing antibodies is a correlate of protection against NiV and HeV in experimentally infected animals. We describe here two cross-reactive F-specific antibodies, 1F5 and 12B2, that neutralize NiV and HeV through inhibition of membrane fusion. Cryo-electron microscopy structures reveal that 1F5 and 12B2 recognize distinct prefusion-specific, conserved quaternary epitopes and lock F in its prefusion conformation. We provide proof-of-concept for using antibody cocktails for neutralizing NiV and HeV and define a roadmap for developing effective countermeasures against these highly pathogenic viruses.


Assuntos
Anticorpos Antivirais/imunologia , Anticorpos Amplamente Neutralizantes/imunologia , Vírus Hendra/imunologia , Vírus Nipah/imunologia , Proteínas Virais de Fusão/imunologia , Animais , Anticorpos Monoclonais Humanizados/imunologia , Células CHO , Cricetulus , Reações Cruzadas , Células HEK293 , Infecções por Henipavirus/imunologia , Infecções por Henipavirus/prevenção & controle , Humanos , Camundongos , Internalização do Vírus
7.
Cell ; 183(6): 1536-1550.e17, 2020 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-33306954

RESUMO

Hendra (HeV) and Nipah (NiV) viruses are emerging zoonotic pathogens in the Henipavirus genus causing outbreaks of disease with very high case fatality rates. Here, we report the first naturally occurring human monoclonal antibodies (mAbs) against HeV receptor binding protein (RBP). All isolated mAbs neutralized HeV, and some also neutralized NiV. Epitope binning experiments identified five major antigenic sites on HeV-RBP. Animal studies demonstrated that the most potent cross-reactive neutralizing mAbs, HENV-26 and HENV-32, protected ferrets in lethal models of infection with NiV Bangladesh 3 days after exposure. We solved the crystal structures of mAb HENV-26 in complex with both HeV-RBP and NiV-RBP and of mAb HENV-32 in complex with HeV-RBP. The studies reveal diverse sites of vulnerability on RBP recognized by potent human mAbs that inhibit virus by multiple mechanisms. These studies identify promising prophylactic antibodies and define protective epitopes that can be used in rational vaccine design.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Vírus Hendra/imunologia , Henipavirus/imunologia , Testes de Neutralização , Vírus Nipah/imunologia , Receptores Virais/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/isolamento & purificação , Antígenos Virais/imunologia , Sítios de Ligação , Ligação Competitiva , Encéfalo/patologia , Quirópteros/virologia , Reações Cruzadas/imunologia , Cristalografia por Raios X , Efrina-B2/metabolismo , Feminino , Furões/virologia , Humanos , Interferometria , Fígado/patologia , Modelos Moleculares , Ligação Proteica , Conformação Proteica , Domínios Proteicos , Receptores Virais/química , Receptores Virais/metabolismo
8.
Annu Rev Virol ; 7(1): 447-473, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32991264

RESUMO

Hendra virus (HeV) and Nipah virus (NiV) are bat-borne zoonotic para-myxoviruses identified in the mid- to late 1990s in outbreaks of severe disease in livestock and people in Australia and Malaysia, respectively. HeV repeatedly re-emerges in Australia while NiV continues to cause outbreaks in South Asia (Bangladesh and India), and these viruses have remained transboundary threats. In people and several mammalian species, HeV and NiV infections present as a severe systemic and often fatal neurologic and/or respiratory disease. NiV stands out as a potential pandemic threat because of its associated high case-fatality rates and capacity for human-to-human transmission. The development of effective vaccines, suitable for people and livestock, against HeV and NiV has been a research focus. Here, we review the progress made in NiV and HeV vaccine development, with an emphasis on those approaches that have been tested in established animal challenge models of NiV and HeV infection and disease.


Assuntos
Doenças Transmissíveis Emergentes/prevenção & controle , Vírus Hendra/imunologia , Infecções por Henipavirus/prevenção & controle , Vírus Nipah/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/imunologia , Quirópteros/virologia , Doenças Transmissíveis Emergentes/imunologia , Doenças Transmissíveis Emergentes/virologia , Modelos Animais de Doenças , Infecções por Henipavirus/imunologia , Humanos , Camundongos , Zoonoses Virais/prevenção & controle , Zoonoses Virais/transmissão
9.
PLoS One ; 15(5): e0232339, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32374743

RESUMO

Habitat-mediated global change is driving shifts in species' distributions which can alter the spatial risks associated with emerging zoonotic pathogens. Many emerging infectious pathogens are transmitted by highly mobile species, including bats, which can act as spill-over hosts for pathogenic viruses. Over three years, we investigated the seroepidemiology of paramyxoviruses and Australian bat lyssavirus in a range-expanding fruit bat, the Grey-headed flying fox (Pteropus poliocephalus), in a new camp in Adelaide, South Australia. Over six, biannual, sampling sessions, we quantified median florescent intensity (MFI) antibody levels for four viruses for a total of 297 individual bats using a multiplex Luminex binding assay. Where appropriate, florescence thresholds were determined using finite mixture modelling to classify bats' serological status. Overall, apparent seroprevalence of antibodies directed at Hendra, Cedar and Tioman virus antigens was 43.2%, 26.6% and 95.7%, respectively. We used hurdle models to explore correlates of seropositivity and antibody levels when seropositive. Increased body condition was significantly associated with Hendra seropositivity (Odds ratio = 3.67; p = 0.002) and Hendra virus levels were significantly higher in pregnant females (p = 0.002). While most bats were seropositive for Tioman virus, antibody levels for this virus were significantly higher in adults (p < 0.001). Unexpectedly, all sera were negative for Australian bat lyssavirus. Temporal variation in antibody levels suggests that antibodies to Hendra virus and Tioman virus may wax and wane on a seasonal basis. These findings suggest a common exposure to Hendra virus and other paramyxoviruses in this flying fox camp in South Australia.


Assuntos
Quirópteros/virologia , Vírus Hendra/isolamento & purificação , Lyssavirus/isolamento & purificação , Animais , Quirópteros/sangue , Quirópteros/imunologia , Quirópteros/fisiologia , Feminino , Vírus Hendra/imunologia , Lyssavirus/imunologia , Masculino , Reprodução , Estudos Soroepidemiológicos
10.
Viruses ; 12(4)2020 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-32340278

RESUMO

The genus Henipavirus (HNVs) includes two fatal viruses, namely Nipah virus (NiV) and Hendra virus (HeV). Since 1994, NiV and HeV have been endemic to the Asia-Pacific region and responsible for more than 600 cases of infections. Two emerging HNVs, Ghana virus (GhV) and Mojiang virus (MojV), are speculated to be associated with unrecognized human diseases in Africa and China, respectively. Despite many efforts to develop vaccines against henipaviral diseases, there is presently no licensed human vaccine. As HNVs are highly pathogenic and diverse, it is necessary to develop universal vaccines to prevent future outbreaks. The attachment enveloped glycoprotein (G protein) of HNVs mediates HNV attachment to the host cell's surface receptors. G proteins have been used as a protective antigen in many vaccine candidates for HNVs. We performed quantitative studies on the antibody responses elicited by the G proteins of NiV, HeV, GhV, and MojV. We found that the G proteins of NiV and HeV elicited only a limited cross-reactive antibody response. Further, there was no cross-protection between MojV, GhV, and highly pathogenic HNVs. We then constructed a bivalent vaccine where the G proteins of NiV and HeV were fused with the human IgG1 Fc domain. The immunogenicity of the bivalent vaccine was compared with that of monovalent vaccines. Our results revealed that the Fc-based bivalent vaccine elicited a potent antibody response against both NiV and HeV. We also constructed a tetravalent Fc heterodimer fusion protein that contains the G protein domains of four HNVs. Immunization with the tetravalent vaccine elicited broad antibody responses against NiV, HeV, GhV, and MojV in mice, indicating compatibility among the four antigens in the Fc-fusion protein. These data suggest that our novel bivalent and tetravalent Fc-fusion proteins may be efficient candidates to prevent HNV infection.


Assuntos
Anticorpos Amplamente Neutralizantes/imunologia , Infecções por Henipavirus/prevenção & controle , Henipavirus/genética , Henipavirus/imunologia , Fragmentos Fc das Imunoglobulinas/imunologia , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Animais , Anticorpos Antivirais/imunologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Vírus Hendra/imunologia , Henipavirus/classificação , Camundongos , Testes de Neutralização , Vírus Nipah/imunologia , Filogenia , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia
11.
PLoS Pathog ; 16(3): e1008412, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32226041

RESUMO

Bats are the natural reservoir host for a number of zoonotic viruses, including Hendra virus (HeV) which causes severe clinical disease in humans and other susceptible hosts. Our understanding of the ability of bats to avoid clinical disease following infection with viruses such as HeV has come predominantly from in vitro studies focusing on innate immunity. Information on the early host response to infection in vivo is lacking and there is no comparative data on responses in bats compared with animals that succumb to disease. In this study, we examined the sites of HeV replication and the immune response of infected Australian black flying foxes and ferrets at 12, 36 and 60 hours post exposure (hpe). Viral antigen was detected at 60 hpe in bats and was confined to the lungs whereas in ferrets there was evidence of widespread viral RNA and antigen by 60 hpe. The mRNA expression of IFNs revealed antagonism of type I and III IFNs and a significant increase in the chemokine, CXCL10, in bat lung and spleen following infection. In ferrets, there was an increase in the transcription of IFN in the spleen following infection. Liquid chromatography tandem mass spectrometry (LC-MS/MS) on lung tissue from bats and ferrets was performed at 0 and 60 hpe to obtain a global overview of viral and host protein expression. Gene Ontology (GO) enrichment analysis of immune pathways revealed that six pathways, including a number involved in cell mediated immunity were more likely to be upregulated in bat lung compared to ferrets. GO analysis also revealed enrichment of the type I IFN signaling pathway in bats and ferrets. This study contributes important comparative data on differences in the dissemination of HeV and the first to provide comparative data on the activation of immune pathways in bats and ferrets in vivo following infection.


Assuntos
Antígenos Virais/imunologia , Vírus Hendra/imunologia , Infecções por Henipavirus/imunologia , Imunidade Celular , Imunidade Inata , Pulmão/imunologia , Modelos Imunológicos , Animais , Antígenos Virais/genética , Quimiocina CXCL10/genética , Quimiocina CXCL10/imunologia , Quirópteros , Furões , Vírus Hendra/genética , Infecções por Henipavirus/genética , Infecções por Henipavirus/patologia , Interferons/genética , Interferons/imunologia , Pulmão/patologia , Pulmão/virologia , Especificidade da Espécie
12.
Proc Natl Acad Sci U S A ; 116(50): 25057-25067, 2019 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-31767754

RESUMO

Nipah virus (NiV) is a highly pathogenic paramyxovirus that causes frequent outbreaks of severe neurologic and respiratory disease in humans with high case fatality rates. The 2 glycoproteins displayed on the surface of the virus, NiV-G and NiV-F, mediate host-cell attachment and membrane fusion, respectively, and are targets of the host antibody response. Here, we provide a molecular basis for neutralization of NiV through antibody-mediated targeting of NiV-F. Structural characterization of a neutralizing antibody (nAb) in complex with trimeric prefusion NiV-F reveals an epitope at the membrane-distal domain III (DIII) of the molecule, a region that undergoes substantial refolding during host-cell entry. The epitope of this monoclonal antibody (mAb66) is primarily protein-specific and we observe that glycosylation at the periphery of the interface likely does not inhibit mAb66 binding to NiV-F. Further characterization reveals that a Hendra virus-F-specific nAb (mAb36) and many antibodies in an antihenipavirus-F polyclonal antibody mixture (pAb835) also target this region of the molecule. Integrated with previously reported paramyxovirus F-nAb structures, these data support a model whereby the membrane-distal region of the F protein is targeted by the antibody-mediated immune response across henipaviruses. Notably, our domain-specific sequence analysis reveals no evidence of selective pressure at this region of the molecule, suggestive that functional constraints prevent immune-driven sequence variation. Combined, our data reveal the membrane-distal region of NiV-F as a site of vulnerability on the NiV surface.


Assuntos
Anticorpos Neutralizantes , Vírus Hendra , Proteínas Virais de Fusão , Internalização do Vírus , Anticorpos Monoclonais , Anticorpos Neutralizantes/química , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/metabolismo , Linhagem Celular Tumoral , Glicosilação , Células HEK293 , Vírus Hendra/química , Vírus Hendra/imunologia , Vírus Hendra/metabolismo , Vírus Hendra/fisiologia , Humanos , Modelos Moleculares , Ligação Proteica , Proteínas Virais de Fusão/química , Proteínas Virais de Fusão/imunologia , Proteínas Virais de Fusão/metabolismo
13.
J Virol Methods ; 274: 113731, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31513861

RESUMO

Maintenance of Hendra virus (HeV) in pteropid bat populations has been associated with spillover events in horses, humans and dogs. Experimental studies have demonstrated infections for several other species including guinea pigs, cats and ferrets. The criteria of a sensitive and specific serological test that is effective for a range of species, but which does not require use of live virus, has not been satisfactorily addressed by currently available tests. We have evaluated the use of two HeV neutralizing monoclonal antibodies (mAbs) in a blocking format enzyme-linked immunosorbent assay (bELISA) to detect serum antibody against a recombinant expressed HeV G protein (sol G) in several animal species. The human mAb m102.4 neutralises both HeV and the closely related Nipah virus (NiV); the mouse mAb 1.2 neutralises only HeV. Given these functional differences, we have investigated both antibodies using a bELISA format. Diagnostic sensitivity (DSe) and diagnostic specificity (DSp) were optimized using individual thresholds for mAb 1.2 and m102.4. For mAb 1.2 the positive threshold of >33% inhibition yielded DSe and DSp values of 100% (95% CI 95.3-100.0) and 99.5 (95% CI 98.8-99.8) respectively; for mAb m102.4 a positive threshold of >49% inhibition gave DSe and DSp values of 100 (95% CI 95.3-100.0) and 99.8 (95% CI 99.2-100.0) respectively. At these thresholds the DSe was 100% for both tests relative to the virus neutralization test. Importantly, the occurrence of false positive reactions did not overlap across the assays. Therefore, by sequential and selective application of these assays, it is possible to identify false positive reactions and achieve a DSp that approximates 100% in the test population.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Vírus Hendra/imunologia , Infecções por Henipavirus/diagnóstico , Infecções por Henipavirus/veterinária , Animais , Anticorpos Monoclonais/imunologia , Antígenos Virais/imunologia , Humanos , Sensibilidade e Especificidade
14.
Aust Vet J ; 96(5): 161-166, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29691855

RESUMO

OBJECTIVE: To determine the antibody responses to a commercial Hendra virus vaccine (Equivac® HeV) in a field environment. METHODS: A group of 61 horses received a primary vaccination course comprising two doses administered 3-6 weeks apart (V1, V2) and a 3rd dose (V3) given 6 months after the second. This was followed by booster vaccinations at 12 monthly intervals (V4, V5). Antibody titres were assessed using a virus-neutralisation test. RESULTS: Neutralising antibodies against HeV were not detected prior to vaccination. Antibodies were detected in 54/57 horses at 3 weeks after V1 and 51/51 had titres ≥ 32 at 8 weeks after V2. At 6 months after V2, antibody titres decreased in most (31/34) horses and were not detected in three horses. A rapid increase in antibody titres was recorded in 35/36 horses at 1 week following V3. By the first annual booster vaccination (V4), antibodies were still detectable in 29/29 horses, although titres had decreased; in 26/29 horses, titres remained ≥ 32. All horses showed an increase in antibody titres after V4. There was no statistically significant increase in mean antibody titre after V5, compared with after V4. CONCLUSION: Horses administered Equivac® HeV, using a primary vaccination course followed by annual booster vaccinations, mounted an effective secondary immune response and acquired antibody responses that were consistent with protective immunity against HeV in the form of virus-neutralising antibodies. No adverse events were observed after vaccine administration.


Assuntos
Anticorpos Neutralizantes/sangue , Vírus Hendra/imunologia , Infecções por Henipavirus/veterinária , Doenças dos Cavalos/imunologia , Doenças dos Cavalos/prevenção & controle , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/sangue , Infecções por Henipavirus/sangue , Infecções por Henipavirus/imunologia , Infecções por Henipavirus/prevenção & controle , Doenças dos Cavalos/sangue , Cavalos , Imunização Secundária/veterinária , Modelos Lineares , Faculdades de Medicina Veterinária , Vacinação , Vacinas Virais/administração & dosagem , Vacinas Virais/sangue
15.
PLoS Negl Trop Dis ; 12(3): e0006343, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29538374

RESUMO

Henipavirus infection causes severe respiratory and neurological disease in humans that can be fatal. To characterize the pathogenic mechanisms of henipavirus infection in vivo, we performed experimental infections in ferrets followed by genome-wide gene expression analysis of lung and brain tissues. The Hendra, Nipah-Bangladesh, and Nipah-Malaysia strains caused severe respiratory and neurological disease with animals succumbing around 7 days post infection. Despite the presence of abundant viral shedding, animal-to-animal transmission did not occur. The host gene expression profiles of the lung tissue showed early activation of interferon responses and subsequent expression of inflammation-related genes that coincided with the clinical deterioration. Additionally, the lung tissue showed unchanged levels of lymphocyte markers and progressive downregulation of cell cycle genes and extracellular matrix components. Infection in the brain resulted in a limited breadth of the host responses, which is in accordance with the immunoprivileged status of this organ. Finally, we propose a model of the pathogenic mechanisms of henipavirus infection that integrates multiple components of the host responses.


Assuntos
Infecções por Henipavirus/genética , Infecções por Henipavirus/imunologia , Henipavirus/fisiologia , Interações Hospedeiro-Patógeno , Transcriptoma , Animais , Encéfalo/metabolismo , Encéfalo/virologia , Ciclo Celular , Modelos Animais de Doenças , Matriz Extracelular/genética , Furões/virologia , Vírus Hendra/imunologia , Vírus Hendra/patogenicidade , Henipavirus/genética , Infecções por Henipavirus/virologia , Humanos , Inflamação , Interferons/genética , Pulmão/metabolismo , Pulmão/virologia , Vírus Nipah/imunologia , Vírus Nipah/patogenicidade , Eliminação de Partículas Virais
16.
J Vet Diagn Invest ; 30(3): 362-369, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29463198

RESUMO

Obtaining statistically sound numbers of sera from Hendra virus (HeV)-infected horses is problematic because affected individuals usually die or are euthanized before developing a serum antibody response. As a consequence, test validation becomes a challenge. Our approach is an extension of OIE principles for provisional recognition and included 7 validation panels tested across multiple laboratories that provided estimates for test performance characteristics. At a 0.4 S/P cutoff, 16 of 19 sera from HeV-infected horses gave positive results in the HeV soluble G, indirect ELISA (HeVsG iELISA; DSe 84.2% [95% CI: 60.4-96.6%]); 463 of 477 non-infected horse sera tested negative (DSp 97.1% [95% CI: 95.1-98.4%]). The HeVsG iELISA eliminated almost all false-positive results from the previously used HeV iELISA, with marginally decreased relative sensitivity. Assay robustness was evaluated in inter-laboratory and proficiency testing panels. The HeVsG iELISA is considered to be fit for purpose for serosurveillance and international movement of horses when virus neutralization is used for follow-up testing of positive or inconclusive serum samples.


Assuntos
Anticorpos Antivirais/sangue , Ensaio de Imunoadsorção Enzimática/veterinária , Vírus Hendra/imunologia , Doenças dos Cavalos/virologia , Animais , Cavalos , Sensibilidade e Especificidade
17.
Aust Vet J ; 96(4): 132-141, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29399777

RESUMO

OBJECTIVE: To evaluate the effect of Equivac® HeV Hendra virus vaccine on Thoroughbred racing performance. DESIGN: Retrospective pre-post intervention study. METHODS: 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. RESULTS: 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). CONCLUSION: 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.


Assuntos
Vírus Hendra/imunologia , Cavalos/fisiologia , Vacinas Virais/efeitos adversos , Animais , Desempenho Atlético , Feminino , Infecções por Henipavirus/imunologia , Infecções por Henipavirus/prevenção & controle , Infecções por Henipavirus/virologia , Doenças dos Cavalos/imunologia , Doenças dos Cavalos/prevenção & controle , Doenças dos Cavalos/virologia , Masculino , Estudos Retrospectivos , Corrida/fisiologia , Vacinas Virais/imunologia , Vacinas Virais/uso terapêutico
18.
Curr Top Microbiol Immunol ; 419: 191-213, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28674944

RESUMO

Hendra and Nipah viruses (family Paramyxoviridae, genus Henipavirus) are zoonotic RNA viruses that cause lethal disease in humans and are designated as Biosafety Level 4 (BSL4) agents. Moreover, henipaviruses belong to the same group of viruses that cause disease more commonly in humans such as measles, mumps and respiratory syncytial virus. Due to the relatively recent emergence of the henipaviruses and the practical constraints of performing functional genomics studies at high levels of containment, our understanding of the henipavirus infection cycle is incomplete. In this chapter we describe recent loss-of-function (i.e. RNAi) functional genomics screens that shed light on the henipavirus-host interface at a genome-wide level. Further to this, we cross-reference RNAi results with studies probing host proteins targeted by henipavirus proteins, such as nuclear proteins and immune modulators. These functional genomics studies join a growing body of evidence demonstrating that nuclear and nucleolar host proteins play a crucial role in henipavirus infection. Furthermore these studies will underpin future efforts to define the role of nucleolar host-virus interactions in infection and disease.


Assuntos
Genômica , Vírus Hendra/imunologia , Infecções por Henipavirus/genética , Infecções por Henipavirus/imunologia , Interações Hospedeiro-Patógeno , MicroRNAs/metabolismo , Vírus Nipah/imunologia , Proteínas Nucleares/metabolismo , Infecções por Henipavirus/metabolismo , Infecções por Henipavirus/virologia , Humanos , MicroRNAs/genética , Proteínas Nucleares/genética
19.
PLoS One ; 12(6): e0180062, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28636633

RESUMO

Hendra virus is a zoonotic paramyxovirus, which causes severe respiratory and neurological disease in horses and humans. Since 2012, the Hendra virus sub-unit G vaccine has been available for horse vaccination in Australia. Uptake of the vaccine has been limited and spill-over events of Hendra virus infection in horses continue to occur. We conducted an online, questionnaire-based cross-sectional study of 376 horse owners belonging to a variety of different equestrian clubs in Queensland, Australia, to identify risk factors for non-vaccination against Hendra virus. A total of 43.1% (N = 162) of horse owners indicated that they currently did not vaccinate against Hendra virus infection, while 56.9% (N = 214) currently vaccinated against Hendra virus infection. A total of 52 risk factors were evaluated relating to equestrian activities, horse management, perceived risk and severity of horse and human infection with Hendra virus, side effects of Hendra vaccination, other vaccinations conducted by horse owners and horse owners' attitudes towards veterinarians. The final multivariable logistics regression model identified the following risk factors associated with increased odds of non-vaccination against Hendra virus: 1) perceived low risk (compared to high) of Hendra virus infection to horses (considering the horse owners' location and management practices) or horse owners were unsure about the risk of infection, 2) perceived moderate severity (compared to very severe or severe) of Hendra virus infection in humans, 3) horse owners non-vaccination of their pets, 4) horse owners non-vaccination against strangles disease in horses, 5) handling of more than three horses per week (compared to one horse only) and 6) perceived attitude that veterinarians had a high motivation of making money from Hendra virus vaccination (compared to veterinarians having a low motivation of making money from Hendra virus vaccination). Horse owners were more likely to vaccinate against Hendra virus if horses were used for dressage, show jumping or eventing. The study also identified horse owners' concerns about side-effects and about the lack of evidence on vaccine efficacy.


Assuntos
Vírus Hendra/imunologia , Infecções por Henipavirus/prevenção & controle , Doenças dos Cavalos/prevenção & controle , Vacinação , Animais , Austrália , Estudos Transversais , Conhecimentos, Atitudes e Prática em Saúde , Infecções por Henipavirus/virologia , Doenças dos Cavalos/virologia , Cavalos , Humanos , Internet , Razão de Chances , Propriedade , Fatores de Risco , Inquéritos e Questionários , Vacinação/efeitos adversos , Vacinação/economia , Médicos Veterinários/economia , Médicos Veterinários/psicologia
20.
Transbound Emerg Dis ; 64(6): 1898-1911, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28054443

RESUMO

Hendra virus was identified in horses and humans in 1994, in Queensland, Australia. Flying foxes are the natural host. Horses are thought to acquire infection by direct or indirect contact with infected flying fox urine. Humans are infected from close contact with infected horses. To reduce risk of infection in horses and humans, Australian horse owners are encouraged to vaccinate horses against the virus and adopt property risk mitigation practices that focus on reducing flying fox horse contact and contamination of horses' environment with flying fox bodily fluids. This study investigates uptake of four Hendra virus risk mitigation practices in a sample of non- and partially vaccinating horse owners living close to previous Hendra virus cases. Protection motivation theory was used to develop a conceptual model to investigate risk perception and coping factors associated with uptake of risk mitigation practices. An online survey was administered via Facebook pages of veterinary clinics close to previous Hendra virus cases. Factors associated with uptake of risk mitigation practices were investigated using univariate and multivariate binary logistic regression. Belief that a risk mitigation practice would be effective in reducing Hendra virus risk was significantly associated with the uptake of that practice. Issues around the practicality of implementing risk mitigation practices were found to be the greatest barrier to uptake. Factors that relate to risk immediacy, such as nearby infection, were identified as more likely to trigger uptake of risk mitigation practices. The role of veterinarians in supporting Hendra risk mitigation was identified as more influential than that of respected others or friends. Findings from this study are being used to assist stakeholders in Australia responsible for promotion of risk mitigation practice in identifying additional pathways and reliable influencing factors that could be utilized for engaging and communicating with horse owners to promote Hendra virus risk mitigation behaviour.


Assuntos
Quirópteros/virologia , Vírus Hendra/imunologia , Infecções por Henipavirus/prevenção & controle , Doenças dos Cavalos/prevenção & controle , Vacinação/veterinária , Vacinas Virais/imunologia , Adulto , Animais , Austrália/epidemiologia , Infecções por Henipavirus/epidemiologia , Infecções por Henipavirus/transmissão , Infecções por Henipavirus/virologia , Doenças dos Cavalos/epidemiologia , Doenças dos Cavalos/transmissão , Doenças dos Cavalos/virologia , Cavalos , Hospitais Veterinários , Humanos , Pessoa de Meia-Idade , Risco , Inquéritos e Questionários , Médicos Veterinários , Zoonoses
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