tetano
Editor, Senior Moderator
Influenza Other Respir Viruses. 2014 Aug 2. doi: 10.1111/irv.12274. [Epub ahead of print]
A promoter mutation in the haemagglutinin segment of influenza A virus generates an effective candidate live attenuated vaccine.
Harvey R1, Johnson RE, MacLellan-Gibson K, Robertson JS, Engelhardt OG.
Author information
Abstract
BACKGROUND:
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.
OBJECTIVES:
It 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).
METHODS:
NIBRG-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.
RESULTS:
NIBRG-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.
CONCLUSIONS:
We demonstrate that NIBRG-93 is an effective live attenuated vaccine virus protecting mice against lethal challenge and reducing virus shedding.
? 2014 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.
KEYWORDS:
Candidate vaccine virus; haemagglutinin; influenza; live attenuated; promoter mutation; vaccine
PMID:
25087607
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25087607
A promoter mutation in the haemagglutinin segment of influenza A virus generates an effective candidate live attenuated vaccine.
Harvey R1, Johnson RE, MacLellan-Gibson K, Robertson JS, Engelhardt OG.
Author information
Abstract
BACKGROUND:
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.
OBJECTIVES:
It 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).
METHODS:
NIBRG-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.
RESULTS:
NIBRG-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.
CONCLUSIONS:
We demonstrate that NIBRG-93 is an effective live attenuated vaccine virus protecting mice against lethal challenge and reducing virus shedding.
? 2014 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.
KEYWORDS:
Candidate vaccine virus; haemagglutinin; influenza; live attenuated; promoter mutation; vaccine
PMID:
25087607
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25087607