Abstract
BackgroundAnnual seasonal and pandemic influenza vaccines need to be produced in a very tight time frame. Haemagglutinin (HA) is the major immunogenic component of influenza vaccines, and there is a lot of interest in improving candidate vaccine viruses.ObjectivesIt has been shown elsewhere that mutations introduced in the non-coding region of influenza genome segments can upregulate protein expression. Our objective was to assess a virus based on the laboratory strain A/PR/8/34 (PR8) containing a modified 3′ non-coding region of RNA segment 4 (haemagglutinin).MethodsNIBRG-93 was generated using reverse genetics. HA protein expression and growth properties were assessed. The virus phenotype suggested that it could be a candidate for use as a live attenuated vaccine, so in vivo studies were performed to assess its suitability.ResultsNIBRG-93 virus has enhanced haemagglutinin production and is significantly attenuated. Electron microscopy (EM) shows that the modified virus produces a large proportion of ‘virus-like particles’ that consist of budded cell membrane covered in HA but lacking M1 protein. The virus was shown to be attenuated in mice and offered complete protection against lethal challenge.ConclusionsWe demonstrate that NIBRG-93 is an effective live attenuated vaccine virus protecting mice against lethal challenge and reducing virus shedding.
Highlights
Influenza virus evolves rapidly due to antigenic drift or shift and annual vaccination remains the most effective protection against the disease
Considerable research goes into improving candidate vaccine viruses (CVVs), the viruses used in the manufacture of vaccine
A useful CVV for inactivated vaccine production needs to provide a high yield of stable haemagglutinin antigen, the major component of inactivated vaccine
Summary
Influenza virus evolves rapidly due to antigenic drift or shift and annual vaccination remains the most effective protection against the disease. Production of seasonal vaccine can only begin once the composition has been agreed and, takes place according to a very tight schedule.[1] Influenza vaccines are most commonly inactivated split or subunit preparations, but more recently there has been an increase in the development and use of live attenuated vaccines.[2]. A useful CVV for inactivated vaccine production needs to provide a high yield of stable haemagglutinin antigen, the major component of inactivated vaccine. A useful candidate for a live attenuated vaccine has to express the recommended HA and NA antigens but retain an attenuated phenotype. Annual seasonal and pandemic influenza vaccines need to be produced in a very tight time frame. Haemagglutinin (HA) is the major immunogenic component of influenza vaccines, and there is a lot of interest in improving candidate vaccine viruses
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