Broad protection against influenza infection by vectored immunoprophylaxis in mice
Neutralizing antibodies that target epitopes conserved among many strains of influenza virus have been recently isolated from humans. Here we demonstrate that adeno-associated viruses (AAV) encoding two such broadly neutralizing antibodies are protective against diverse influenza strains. Serum from mice that received a single intramuscular AAV injection efficiently neutralized all H1, H2 and H5 influenza strains tested. After infection with diverse strains of H1N1 influenza, treated mice showed minimal weight loss and lung inflammation. Protection lasted for at least 11 months after AAV injection. Notably, even immunodeficient and older mice were protected by this method, suggesting that expression of a monoclonal antibody alone is sufficient to protect mice from illness. If translated to humans, this prophylactic approach may be uniquely capable of protecting immunocompromised or elderly patient populations not reliably protected by existing vaccines.
© 2013 Nature Publishing Group. Received 25 February; accepted 21 May; published online 9 June 2013. The authors wish to thank D. Majumdar, A. Sigal and J. Zhao for their helpful comments, and other members of the Baltimore Lab for their assistance in carrying out this work. This project was supported by a contract from the National Institute of Allergy and Infectious Disease (NIAID) and by the Joint Center for Translational Medicine as well as a Caltech Translational Innovation Partnership Award. A.B.B. is supported by the amfAR postdoctoral research fellowship no. 107756-47-RFVA. D.S.R. is supported by career development award 1K08CA133521 from the National Institutes of Health. The bidirectional reverse-genetics plasmids29 from the PR/34 strain of influenza were a kind gift from R. Webby of St. Jude Children's Research Hospital. The pHW2000 plasmid was a kind gift from Y. Kawaoka of the University of Wisconsin. Author Contributions: A.B.B. conceived the study, designed and performed experiments, and wrote the manuscript. J.D.B. conceived the study and designed experiments, C.M.H. performed experiments, D.S.R. performed histological analysis, and D.B. conceived the study and wrote the manuscript.
Accepted Version - nihms566395.pdf
Supplemental Material - nbt.2618-S1.pdf