This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Parkin, N. T. Articles by Coelingh, K. Search for Related Content PubMed PubMed Citation Articles by Parkin, N. T. Articles by Coelingh, K.

 Previous Article  |  Next Article 

J. Virol., 04 1997, 2772-2778, Vol 71, No. 4
Copyright © 1997, American Society for Microbiology

Genetically engineered live attenuated influenza A virus vaccine candidates

NT Parkin, P Chiu and K Coelingh
AVIRON, Mountain View, California 94043, USA.

We have generated new influenza A virus live attenuated vaccine candidates by site-directed mutagenesis and reverse genetics. By mutating specific amino acids in the PB2 polymerase subunit, two temperature-sensitive (ts) attenuated viruses were obtained. Both candidates have 38 degrees C shutoff temperatures in MDCK cells, are attenuated in the respiratory tracts of mice and ferrets, and have very low reactogenicity in ferrets. Infection of mice or ferrets with either mutant conferred significant protection from challenge with the homologous wild-type virus. Three tests for genetic stability were used to assess the propensity for reversion to virulence: 14 days of replication in nude mice, growth at 37 degrees C in tissue culture, and serial passage in ferrets. One candidate, which contains mutations intended to reduce the ability of PB2 to bind to cap structures, was stable in all three assays, whereas the second candidate, which contains mutations found only in other ts strains of influenza virus, lost its ts phenotype in the last two assays. This approach has therefore enabled the creation of live attenuated influenza A virus vaccine candidates suitable for human testing.

This article has been cited by other articles:

• Wang, S., Taaffe, J., Parker, C., Solorzano, A., Cao, H., Garcia-Sastre, A., Lu, S. (2006). Hemagglutinin (HA) Proteins from H1 and H3 Serotypes of Influenza A Viruses Require Different Antigen Designs for the Induction of Optimal Protective Antibody Responses as Studied by Codon-Optimized HA DNA Vaccines. J. Virol. 80: 11628-11637 [Abstract] [Full Text]  
• Neumann, G., Whitt, M. A., Kawaoka, Y. (2002). A decade after the generation of a negative-sense RNA virus from cloned cDNA - what have we learned?. J. Gen. Virol. 83: 2635-2662 [Abstract] [Full Text]  
• Massin, P., van der Werf, S., Naffakh, N. (2001). Residue 627 of PB2 Is a Determinant of Cold Sensitivity in RNA Replication of Avian Influenza Viruses. J. Virol. 75: 5398-5404 [Abstract] [Full Text]  
• Solorzano, A., Zheng, H., Fodor, E., Brownlee, G. G., Palese, P., García-Sastre, A. (2000). Reduced levels of neuraminidase of influenza A viruses correlate with attenuated phenotypes in mice. J. Gen. Virol. 81: 737-742 [Abstract] [Full Text]