Permissible variation in the 3' non-coding region of the haemagglutinin genome segment of the H5N1 candidate influenza vaccine virus NIBRG-14 [corrected]

PLoS One. 2012;7(5):e36241. doi: 10.1371/journal.pone.0036241. Epub 2012 May 11.

Abstract

The candidate H5N1 vaccine virus NIBRG-14 was created in response to a call from the World Health Organisation in 2004 to prepare candidate vaccine viruses (CVVs) to combat the threat of an H5N1 pandemic. NIBRG-14 was created by reverse genetics and is composed of the neuraminidase (NA) and modified haemagglutinin (HA) genes from A/Vietnam/1194/2004 and the internal genes of PR8, a high growing laboratory adapted influenza A(H1N1) strain. Due to time constraints, the non-coding regions (NCRs) of A/Vietnam/1194/2004 HA were not determined prior to creating NIBRG-14. Consequently, the sequence of the primers used to clone the modified A/Vietnam/1194/2004 HA was based upon previous experience of cloning H5N1 viruses. We report here that the HA 3' NCR sequence of NIBRG-14 is different to that of the parental wild type virus A/Vietnam/1194/2004; however this does not appear to impact on its growth or antigen yield. We introduced additional small changes into the 3'NCR of NIBRG-14; these had only minor effects on viral growth and antigen content. These findings may serve to assure the influenza vaccine community that generation of CVVs using best-guess NCR sequences, based on sequence alignments, are likely to produce robust viruses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions*
  • Animals
  • Base Sequence
  • Cell Line
  • Chick Embryo
  • Chlorocebus aethiops
  • Dogs
  • Genetic Engineering
  • Genetic Variation
  • Genome, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics*
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Humans
  • Influenza A Virus, H5N1 Subtype / genetics*
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Influenza A Virus, H5N1 Subtype / pathogenicity
  • Influenza A Virus, H5N1 Subtype / physiology
  • Influenza Vaccines / genetics*
  • Influenza Vaccines / immunology*
  • Molecular Sequence Data
  • RNA, Viral / genetics
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Vero Cells
  • Virus Cultivation
  • Virus Replication

Substances

  • 3' Untranslated Regions
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
  • RNA, Viral
  • Vaccines, Synthetic