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Статья
Preclinical evaluation of a replication-deficient intranasal ΔNS1 H5N1 influenza vaccine
2021
Background: We developed a novel intranasal influenza vaccine approach that is based on the construction of replication-deficient vaccine viruses that lack the entire NS1 gene (ΔNS1 virus). We previously showed that these viruses undergo abortive replication in the respiratory tract of animals. The local release of type I interferons and other cytokines and chemokines in the upper respiratory tract may have a "self-adjuvant effect", in turn increasing vaccine immunogenicity. As a result, ΔNS1 viruses elicit strong B- and T- cell mediated immune responses. Methodology/Principal Findings: We applied this technology to the development of a pandemic H5N1 vaccine candidate. The vaccine virus was constructed by reverse genetics in Vero cells, as a 5:3 reassortant, encoding four proteins HA, NA, M1, and M2 of the A/Vietnam/1203/04 virus while the remaining genes were derived from IVR-116. The HA cleavage site was modified in a trypsin dependent manner, serving as the second attenuation factor in addition to the deleted NS1 gene. The vaccine candidate was able to grow in the Vero cells that were cultivated in a serum free medium to titers exceeding 8 log10 TCID50/ml. The vaccine virus was replication deficient in interferon competent cells and did not lead to viral shedding in the vaccinated animals. The studies performed in three animal models confirmed the safety and immunogenicity of the vaccine. Intranasal immunization protected ferrets and mice from being infected with influenza H5 viruses of different clades. In a primate model (Macaca mulatta), one dose of vaccine delivered intranasally was sufficient for the induction of antibodies against homologous A/Vietnam/1203/04 and heterologous A/Indonesia/5/05 H5N1 strains. Conclusion/Significance: Our findings show that intranasal immunization with the replication deficient H5N1 ΔNS1 vaccine candidate is sufficient to induce a protective immune response against H5N1 viruses. This approach might be attractive as an alternative to conventional influenza vaccines. Clinical evaluation of ΔNS1 pandemic and seasonal influenza vaccine candidates are currently in progress. © 2009 Romanova et al.
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Версии
- 1. Version of Record от 2021-04-27
Метаданные
Название журнала
- PLoS ONE
Том
- 4
Выпуск
- 6
Страницы
- -
Ключевые слова
- influenza vaccine; nonstructural protein 1; influenza vaccine; Influenza virus hemagglutinin; animal cell; animal experiment; animal model; animal tissue; antibody production; article; chicken; controlled study; cross reaction; drug safety; female; ferret; genetic reassortment; human; human cell; immunogenicity; influenza; influenza vaccination; Influenza virus A H5N1; innate immunity; interferon induction; Macaca; male; mouse; nonhuman; nucleotide sequence; single drug dose; virus replication; virus virulence; animal; bronchus; cell line; Cercopithecus; chemistry; cytology; dog; drug screening; epithelium cell; genetics; intranasal drug administration; macrophage; metabolism; Vero cell; virology; Animalia; Macaca mulatta; Mus; Mustela; Primates; Administration, Intranasal; Animals; Bronchi; Cell Line; Cercopithecus aethiops; Chickens; Dogs; Drug Evaluation, Preclinical; Epithelial Cells; Ferrets; Hemagglutinin Glycoproteins, Influenza Virus; Humans; Influenza A Virus, H5N1 Subtype; Influenza Vaccines; Macrophages; Mice; Vero Cells; Virus Replication
Тип документа
- journal article
Тип лицензии Creative Commons
- CC
Правовой статус документа
- Свободная лицензия
Источник
- scopus
