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Glycosylation generates an efficacious and immunogenic vaccine against H7N9 influenza virus
- Source :
- PLoS Biology, Vol 18, Iss 12, p e3001024 (2020), PLoS Biology
- Publication Year :
- 2020
- Publisher :
- Public Library of Science (PLoS), 2020.
-
Abstract
- Zoonotic avian influenza viruses pose severe health threats to humans. Of several viral subtypes reported, the low pathogenic avian influenza H7N9 virus has since February 2013 caused more than 1,500 cases of human infection with an almost 40% case-fatality rate. Vaccination of poultry appears to reduce human infections. However, the emergence of highly pathogenic strains has increased concerns about H7N9 pandemics. To develop an efficacious H7N9 human vaccine, we designed vaccine viruses by changing the patterns of N-linked glycosylation (NLG) on the viral hemagglutinin (HA) protein based on evolutionary patterns of H7 HA NLG changes. Notably, a virus in which 2 NLG modifications were added to HA showed higher growth rates in cell culture and elicited more cross-reactive antibodies than did other vaccine viruses with no change in the viral antigenicity. Developed into an inactivated vaccine formulation, the vaccine virus with 2 HA NLG additions exhibited much better protective efficacy against lethal viral challenge in mice than did a vaccine candidate with wild-type (WT) HA by reducing viral replication in the lungs. In a ferret model, the 2 NLG-added vaccine viruses also induced hemagglutination-inhibiting antibodies and significantly suppressed viral replication in the upper and lower respiratory tracts compared with the WT HA vaccines. In a mode of action study, the HA NLG modification appeared to increase HA protein contents incorporated into viral particles, which would be successfully translated to improve vaccine efficacy. These results suggest the strong potential of HA NLG modifications in designing avian influenza vaccines.<br />This study shows that changing the pattern of N-glycosylation of the pathogenic avian influenza H7N9 virus hemagglutinin protein increases the amount of hemagglutinin incorporated into the viral membrane; the candidate vaccine virus induces neutralizing antibodies and protects animal models from lethal viral challenge.
- Subjects :
- 0301 basic medicine
RNA viruses
Glycosylation
Physiology
Cross Protection
viruses
Hemagglutinin Glycoproteins, Influenza Virus
Chick Embryo
medicine.disease_cause
Antibodies, Viral
Influenza A Virus, H7N9 Subtype
Biochemistry
Mice
0302 clinical medicine
Immunogenicity, Vaccine
Medical Conditions
Immune Physiology
Chlorocebus aethiops
Influenza A virus
Medicine and Health Sciences
Public and Occupational Health
030212 general & internal medicine
Biology (General)
Pathology and laboratory medicine
Vaccines
Immune System Proteins
General Neuroscience
Viral Vaccine
Vaccination
Medical microbiology
Vaccination and Immunization
Body Fluids
Infectious Diseases
Blood
Influenza Vaccines
Viruses
Pathogens
Anatomy
General Agricultural and Biological Sciences
Research Article
Infectious Disease Control
QH301-705.5
Guinea Pigs
Immunology
Biology
Cross Reactions
Microbiology
General Biochemistry, Genetics and Molecular Biology
Virus
Antibodies
H7N9
03 medical and health sciences
Virology
Influenza, Human
Vaccine Development
medicine
Animals
Humans
Influenza viruses
Antigens
Vero Cells
General Immunology and Microbiology
Ferrets
Organisms
Viral pathogens
Biology and Life Sciences
Proteins
Viral Vaccines
Blood Serum
Vaccine efficacy
Influenza A virus subtype H5N1
Viral Replication
Microbial pathogens
030104 developmental biology
HEK293 Cells
Viral replication
A549 Cells
Inactivated vaccine
Preventive Medicine
Immune Serum
Orthomyxoviruses
Subjects
Details
- Language :
- English
- ISSN :
- 15457885 and 15449173
- Volume :
- 18
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- PLoS Biology
- Accession number :
- edsair.doi.dedup.....2ff18a2d8230b1ef414f8ded8685d7f0