Objective: To explore a common B-and T-cell epitope-based vaccine that can elicit an immune response against encephalitis causing genus Henipaviruses, Hendra virus(He V) and Nipah virus(Ni V). Methods: Membrane protei...Objective: To explore a common B-and T-cell epitope-based vaccine that can elicit an immune response against encephalitis causing genus Henipaviruses, Hendra virus(He V) and Nipah virus(Ni V). Methods: Membrane proteins F, G and M of He V and Ni V were retrieved from the protein database and subjected to different bioinformatics tools to predict antigenic B-cell epitopes. Best B-cell epitopes were then analyzed to predict their T-cell antigenic potentiality. Antigenic B-and T-cell epitopes that shared maximum identity with He V and Ni V were selected. Stability of the selected epitopes was predicted. Finally, the selected epitopes were subjected to molecular docking simulation with HLA-DR to confirm their antigenic potentiality in silico. Results: One epitope from G proteins, one from M proteins and none from F proteins were selected based on their antigenic potentiality. The epitope from the G proteins was stable whereas that from M was unstable. The M-epitope was made stable by adding flanking dipeptides. The 15-mer G-epitope(VDPLRVQWRNNSVIS) showed at least 66% identity with all Ni V and He V G protein sequences, while the 15-mer M-epitope(GKLEFRRNNAIAFKG) with the dipeptide flanking residues showed 73% identity with all Ni V and He V M protein sequences available in the database. Molecular docking simulation with most frequent MHC class-II(MHC II) and class-I(MHC I) molecules showed that these epitopes could bind within HLA binding grooves to elicit an immune response. Conclusions: Data in our present study revealed the notion that the epitopes from G and M proteins might be the target for peptide-based subunit vaccine design against He V and Ni V. However, the biochemical analysis is necessary to experimentally validate the interaction of epitopes individually with the MHC molecules through elucidation of immunity induction.展开更多
Hendra virus,a novel member of the family Paramyxovirus that has emerged from bats in Australia,causes fatal disease in livestock and humans. Eleven spillover events have been identified since the first description of...Hendra virus,a novel member of the family Paramyxovirus that has emerged from bats in Australia,causes fatal disease in livestock and humans. Eleven spillover events have been identified since the first description of the virus in 1994,resulting in a total of 37 equine cases and six human cases. All human cases have been attributed to exposure to infected horses;there is no evidence of bat-to-human or human-to-human transmission. Low infectivity and a high case fatality rate are features of Hendra virus infection in both horses and humans. The temporal pattern of spillover events suggests seasonal factors(plausibly be environmental,biological or ecological) as the proximate triggers for spillover. Minimisation of the future occurrence and impact of Hendra virus infections requires an understanding of the ecology of flying foxes,of virus infection dynamics in flying foxes,and of the factors that promote spillover. Management strategies seek to minimize the opportunity for effective contact between bats and horses,and limit potential horse-to-horse and horse-to-human transmission. Incomplete knowledge of the ecology of the virus,of the proximate factors associated with spillover,and the inherent difficulties of effectively managing wild populations,preclude a management approach targeted at bats.展开更多
Nipah virus(NiV)and Hendra virus(HeV)are highly pathogenic henipaviruses within the Paramyxoviridae family,causing severe respiratory and neurological diseases in humans and animals with fatality rates up to 75%,and n...Nipah virus(NiV)and Hendra virus(HeV)are highly pathogenic henipaviruses within the Paramyxoviridae family,causing severe respiratory and neurological diseases in humans and animals with fatality rates up to 75%,and no licensed human vaccines or therapeutics.In this study,we identified a unique vulnerable epitope on the NiV attachment glycoprotein(G)recognized by the potent neutralizing antibody 14F8,which targets a receptor-binding site and neutralizes NiV effectively.Using the 2.8Åcrystal structure of the 14F8 Fab–NiV-G complex as a guide,we reconstructed this epitope on HeV-G via a single amino acid substitution(S586N),creating the HeV-G_(S586N) mutant.Immunization with HeV-G_(S586N) in BALB/c mice and cynomolgus monkeys elicited robust,broadly neutralizing antibody responses against both NiV and HeV,achieving higher NiV-neutralizing titers post-prime compared to wild-type HeV-G,as confirmed by pseudovirus and live-virus assays.Crystal structures of HeV-G_(S586N)(3.3Å)and its 14F8 complex(3.2Å)showed the S586N substitution induced a 9Åconformational rearrangement inβ-propeller blade 6,reshaping the molecular skeleton and solvent-accessible surface without direct N586–14F8 interaction,thus mimicking the NiV epitope.These findings position HeV-G_(S586N) as a promising broad-spectrum antigen for henipavirus prevention and demonstrate the value of structure-guided epitope reconstruction in universal vaccine design for emerging viral threats.展开更多
Hendra virus(HeV)is a highly pathogenic virus causing fatalities in humans and horses for which the natural reservoir is pteropid bats(also called flying foxes).Anthropogenic stressors,such as land-use change and biod...Hendra virus(HeV)is a highly pathogenic virus causing fatalities in humans and horses for which the natural reservoir is pteropid bats(also called flying foxes).Anthropogenic stressors,such as land-use change and biodiversity loss,may increase the risk of cross-species transmission from the reservoir to horses by increasing the activity of the reservoir and subsequently its contact with horses.However,only a few studies have investigated the effect of environmental changes on spillover events.This study aims to investigate the impacts of deforestation and predator species richness on HeV spillover in Australia.展开更多
文摘Objective: To explore a common B-and T-cell epitope-based vaccine that can elicit an immune response against encephalitis causing genus Henipaviruses, Hendra virus(He V) and Nipah virus(Ni V). Methods: Membrane proteins F, G and M of He V and Ni V were retrieved from the protein database and subjected to different bioinformatics tools to predict antigenic B-cell epitopes. Best B-cell epitopes were then analyzed to predict their T-cell antigenic potentiality. Antigenic B-and T-cell epitopes that shared maximum identity with He V and Ni V were selected. Stability of the selected epitopes was predicted. Finally, the selected epitopes were subjected to molecular docking simulation with HLA-DR to confirm their antigenic potentiality in silico. Results: One epitope from G proteins, one from M proteins and none from F proteins were selected based on their antigenic potentiality. The epitope from the G proteins was stable whereas that from M was unstable. The M-epitope was made stable by adding flanking dipeptides. The 15-mer G-epitope(VDPLRVQWRNNSVIS) showed at least 66% identity with all Ni V and He V G protein sequences, while the 15-mer M-epitope(GKLEFRRNNAIAFKG) with the dipeptide flanking residues showed 73% identity with all Ni V and He V M protein sequences available in the database. Molecular docking simulation with most frequent MHC class-II(MHC II) and class-I(MHC I) molecules showed that these epitopes could bind within HLA binding grooves to elicit an immune response. Conclusions: Data in our present study revealed the notion that the epitopes from G and M proteins might be the target for peptide-based subunit vaccine design against He V and Ni V. However, the biochemical analysis is necessary to experimentally validate the interaction of epitopes individually with the MHC molecules through elucidation of immunity induction.
文摘Hendra virus,a novel member of the family Paramyxovirus that has emerged from bats in Australia,causes fatal disease in livestock and humans. Eleven spillover events have been identified since the first description of the virus in 1994,resulting in a total of 37 equine cases and six human cases. All human cases have been attributed to exposure to infected horses;there is no evidence of bat-to-human or human-to-human transmission. Low infectivity and a high case fatality rate are features of Hendra virus infection in both horses and humans. The temporal pattern of spillover events suggests seasonal factors(plausibly be environmental,biological or ecological) as the proximate triggers for spillover. Minimisation of the future occurrence and impact of Hendra virus infections requires an understanding of the ecology of flying foxes,of virus infection dynamics in flying foxes,and of the factors that promote spillover. Management strategies seek to minimize the opportunity for effective contact between bats and horses,and limit potential horse-to-horse and horse-to-human transmission. Incomplete knowledge of the ecology of the virus,of the proximate factors associated with spillover,and the inherent difficulties of effectively managing wild populations,preclude a management approach targeted at bats.
基金funding support from the National Natural Science Foundation of China(32200762)the Defense Industrial Technology Development Program(JCKY2020802B001).
文摘Nipah virus(NiV)and Hendra virus(HeV)are highly pathogenic henipaviruses within the Paramyxoviridae family,causing severe respiratory and neurological diseases in humans and animals with fatality rates up to 75%,and no licensed human vaccines or therapeutics.In this study,we identified a unique vulnerable epitope on the NiV attachment glycoprotein(G)recognized by the potent neutralizing antibody 14F8,which targets a receptor-binding site and neutralizes NiV effectively.Using the 2.8Åcrystal structure of the 14F8 Fab–NiV-G complex as a guide,we reconstructed this epitope on HeV-G via a single amino acid substitution(S586N),creating the HeV-G_(S586N) mutant.Immunization with HeV-G_(S586N) in BALB/c mice and cynomolgus monkeys elicited robust,broadly neutralizing antibody responses against both NiV and HeV,achieving higher NiV-neutralizing titers post-prime compared to wild-type HeV-G,as confirmed by pseudovirus and live-virus assays.Crystal structures of HeV-G_(S586N)(3.3Å)and its 14F8 complex(3.2Å)showed the S586N substitution induced a 9Åconformational rearrangement inβ-propeller blade 6,reshaping the molecular skeleton and solvent-accessible surface without direct N586–14F8 interaction,thus mimicking the NiV epitope.These findings position HeV-G_(S586N) as a promising broad-spectrum antigen for henipavirus prevention and demonstrate the value of structure-guided epitope reconstruction in universal vaccine design for emerging viral threats.
基金supported by a National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(no.NRF-2021R1C1C2012611)
文摘Hendra virus(HeV)is a highly pathogenic virus causing fatalities in humans and horses for which the natural reservoir is pteropid bats(also called flying foxes).Anthropogenic stressors,such as land-use change and biodiversity loss,may increase the risk of cross-species transmission from the reservoir to horses by increasing the activity of the reservoir and subsequently its contact with horses.However,only a few studies have investigated the effect of environmental changes on spillover events.This study aims to investigate the impacts of deforestation and predator species richness on HeV spillover in Australia.
