Recombinant neuraminidase vaccine protects against lethal influenza

Vaccine. 1996 Apr;14(6):561-9. doi: 10.1016/0264-410x(95)00157-v.


The N2 neuraminidase gene of A/Victoria/3/75 influenza virus was engineered to encode a secretable protein (NAs) by replacing the natural N-terminal membrane anchor sequence with the cleavable signal sequence of the corresponding influenza hemagglutinin gene. Soluble NAs was expressed by a baculovirus/insect cell system and accumulated in the medium at levels between 6 and 8 microgram ml-1. A combination of biochemical and standard chromatographic techniques allowed the purification of NAs to homogeneity. Cross-linking analysis indicated that NAs was partly recovered as an authentic tetrameric protein, while the remaining fraction was composed of dimeric molecules and small amounts of monomeric NAs. Purified NAs was supplemented with low-reactogenic adjuvants and used to immunize mice. After a challenge infection with a lethal dose of homologous mouse-adapted X47 influenza virus, vaccinated animals showed resistance against severe disease symptoms and were protected from lethality. Based on the results of a passive immunization experiment, it may be concluded that performed antibody plays a central role in the mechanism by which vaccination with NAs confers viral protection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Immune Sera / administration & dosage
  • Immunization, Passive
  • Influenza A virus / genetics*
  • Influenza A virus / immunology*
  • Influenza Vaccines / genetics*
  • Influenza Vaccines / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Neuraminidase / chemistry
  • Neuraminidase / genetics*
  • Neuraminidase / immunology*
  • Neuraminidase / isolation & purification
  • Orthomyxoviridae Infections / mortality
  • Orthomyxoviridae Infections / prevention & control*
  • Recombinant Fusion Proteins / chemical synthesis
  • Recombinant Fusion Proteins / metabolism
  • Vaccines, Synthetic / immunology*


  • Immune Sera
  • Influenza Vaccines
  • Recombinant Fusion Proteins
  • Vaccines, Synthetic
  • Neuraminidase