Generation of an attenuated H5N1 avian influenza virus vaccine with all eight genes from avian viruses
| Autor: | Sujuan Chen, Jianhong Lu, Xiaorong Zhang, Xiu Fan Liu, Huoying Shi, Lei Sun |
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| Rok vydání: | 2007 |
| Předmět: |
Genes
Viral viruses animal diseases Orthomyxoviridae Hemagglutinin Glycoproteins Influenza Virus Biology Vaccines Attenuated Virus Replication medicine.disease_cause H5N1 genetic structure Virus Microbiology Mice Formaldehyde Influenza Human Reassortant Viruses medicine Influenza A virus Animals Humans Amino Acid Sequence Mice Inbred BALB C Attenuated vaccine Base Sequence Influenza A Virus H5N1 Subtype General Veterinary General Immunology and Microbiology Public Health Environmental and Occupational Health virus diseases biology.organism_classification Virology Influenza A virus subtype H5N1 Infectious Diseases Vaccines Inactivated Influenza Vaccines Influenza in Birds DNA Viral Inactivated vaccine Molecular Medicine Female Chickens |
| Zdroj: | Vaccine. 25:7379-7384 |
| ISSN: | 0264-410X |
| DOI: | 10.1016/j.vaccine.2007.08.011 |
| Popis: | In the face of disease outbreaks in poultry and the potential pandemic threat to humans caused by the highly pathogenic avian influenza viruses (HPAIVs) of H5N1 subtype, improvement in biosecurity and the use of inactivated vaccines are two main options for the control of this disease. Vaccine candidates of influenza A viruses of H5N1 subtype have been generated in several laboratories by plasmid-based reverse genetics with hemagglutinin (HA) and neuraminidase (NA) genes from the epidemic strains of avian viruses in a background of internal genes from the vaccine donor strain of human strains, A/Puerto Rico/8/34 (PR8). These reassortant viruses containing genes from both avian and human viruses might impose biosafety concerns, also may be do if C4/F AIV would be a live attenuated vaccine or cold-adaptive strain vaccine. In order to generate better and safer vaccine candidate viruses, we genetically constructed attenuated reassortant H5N1 influenza A virus, designated as C4/F AIV, by plasmid-based reverse genetics with all eight genes from the avian strains. The C4/F AIV virus contained HA and NA genes from an epidemic strain A/Chicken/Huadong/04 (H5N1) (C4/H5N1) in a background of internal genes derived from a low pathogenic strain of A/Chicken/F/98(H9N2). The reassortant virus was attenuated by removal of the multibasic amino acid motif in the HA gene by mutation and deletion (from PQRERRRKKR (downward arrow) G to PQIETR (downward arrow) G). The intravenous pathogenicity index (IVPI) of C4/F AIV virus was 0, whereas that of the donor virus C4/H5N1 was 3.0. The virus HA titer of C4/H5N1 in the allantoic fluid from infected embryonated eggs was as high as 1:2048. The inactivated vaccine prepared from the reassortant virus C4/F AIV-induced high HI titer in vaccinated chickens and gave 100% protection when challenged with highly pathogenic avian influenza virus of H5N1 subtype. |
| Databáze: | OpenAIRE |
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