Two independent teams have shown proof of
concept that gene transfer could be used to establish broad protection against
influenza A viruses.1,2 Both laboratories are working to move their influenza A virus hemagglutinin-expressing vectors into humans for immunogenicity and
The Wilson team showed that mice receiving prophylactic nasal
doses of AAV2/9 expressing FI6 survived a lethal influenza challenge three,
four or seven days later. Mice pretreated one day before lethal challenge did
not survive, although the symptoms of infection were delayed.
The Baltimore group showed that mice intramuscularly injected
with AAV2/8 encoding F10 were protected from lethal challenge with either of
three different influenza H1 strains. Protection lasted for at least 11 months
after gene transfer.
For both gene transfer approaches, showing adequate
expression and safety in the clinic should be the next step, according to Gary
Nabel, SVP and CSO of Sanofi.
Baas, T. SciBX 6(24); doi:10.1038/scibx.2013.591
Published online June 20, 2013
1. Limberis, M.P. et
al. Sci. Transl. Med.; published online May 29, 2013;
Contact: Maria P. Limberis, University of Pennsylvania, Philadelphia, Pa.
Contact: James M. Wilson, same affiliation as above
2. Balazs, A.B. et al.
Nat. Biotechnol.; published online June 2, 2013; doi:10.1038/nbt.2618
Contact: David Baltimore, California Institute of Technology, Pasadena,
3. Dreyfus, C. et al.
Science 337, 1343-1348 (2012)
4. Baas, T. SciBX 5(33);
5. Corti, D. et al.
Science 333, 850-856 (2011)
6. Sui, J. et al. Nat.
Struct. Mol. Biol. 16, 265-273 (2009)
7. Limberis, M.P. &
Wilson, J.M. Proc. Natl. Acad. Sci. USA 103, 12993-12998 (2006)
8. Balazs, A.B. et al.
Nature 481, 81-84 (2011)
9. Johnson, P.R. et al.
Nat. Med. 15, 901-906 (2009)
AND INSTITUTIONS MENTIONED
California Institute of Technology, Pasadena, Calif.
The Children's Hospital of Philadelphia Research Institute, Philadelphia, Pa.
Humabs BioMed S.A., Bellizona, Switzerland
Icahn School of Medicine at Mount Sinai, New York, N.Y.
National Institutes of Health, Bethesda, Md.
ReGenX Biosciences LLC, Washington, D.C.
(Euronext:SAN; NYSE:SNY), Paris, France
University of Pennsylvania, Philadelphia, Pa.