Abstract
The unprecedented emergence in Asia of multiple avian influenza virus (AIV) subtypes with a broad host range poses a major challenge in the design of vaccination strategies that are both effective and available in a timely manner. The present study focused on the protective effects of a genetically modified AIV as a source for the preparation of vaccines for epidemic and pandemic influenza. It has previously been demonstrated that a live attenuated AIV based on the internal backbone of influenza A/Guinea fowl/Hong Kong/WF10/99 (H9N2), called WF10att, is effective at protecting poultry species against low- and high-pathogenicity influenza strains. More importantly, this live attenuated virus provided effective protection when administered in ovo. In order to characterize the WF10att backbone further for use in epidemic and pandemic influenza vaccines, this study evaluated its protective effects in mice. Intranasal inoculation of modified attenuated viruses in mice provided adequate protective immunity against homologous lethal challenges with both the wild-type influenza A/WSN/33 (H1N1) and A/Vietnam/1203/04 (H5N1) viruses. Adequate heterotypic immunity was also observed in mice vaccinated with modified attenuated viruses carrying H7N2 surface proteins. The results presented in this report suggest that the internal genes of a genetically modified AIV confer similar protection in a mouse model and thus could be used as a master donor strain for the generation of live attenuated vaccines for epidemic and pandemic influenza.
Highlights
In the 20th century, humans experienced three pandemics of influenza with significant death tolls (Horimoto & Kawaoka, 2001)
The emergence of highly pathogenic H5N1 avian influenza virus (AIV) in Asia, with an unusually broad host range and the ability to infect and kill people, has raised concerns that another pandemic is looming over us (Horimoto & Kawaoka, 2001)
Our results showed that genetically modified WF10 reassortant viruses induced protective immunity against the highly lethal influenza A/WSN/33 (H1N1) and A/Vietnam/ 1203/04 (H5N1) strains in mice
Summary
In the 20th century, humans experienced three pandemics of influenza with significant death tolls (Horimoto & Kawaoka, 2001). FluMist is a live attenuated influenza vaccine composed of the three dominant circulating strains of human influenza virus types A and B. This vaccine has been shown to be efficacious and safe for delivery in children and adults aged 5–49 and is not transmissible to susceptible contacts (Belshe, 2004; Harper et al, 2004). The two type A influenza viruses present within the FluMist vaccine are reassortants containing the surface genes of the currently circulating H1N1 and H3N2 strains and six internal genes from the master donor virus influenza A/Ann Arbor/6/60 (H2N2) (MDV-A) with a cold-adapted (ca), temperature-sensitive (ts) and attenuated (att) phenotype (Maassab, 1967)
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