Broad protection against influenza infection by vectored immunoprophylaxis in mice

被引:107
作者
Balazs, Alejandro B. [1 ]
Bloom, Jesse D. [2 ]
Hong, Christin M. [1 ]
Rao, Dinesh S. [3 ]
Baltimore, David [1 ]
机构
[1] CALTECH, Div Biol, Pasadena, CA 91125 USA
[2] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98104 USA
[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA
基金
美国国家卫生研究院;
关键词
MEDIATED GENE-TRANSFER; A VIRUS; ANTIBODY; EVOLUTION; H5N1;
D O I
10.1038/nbt.2618
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
引用
收藏
页码:647 / U110
页数:8
相关论文
共 30 条
[1]  
[Anonymous], 1993, MMWR Recomm Rep, V42, P1
[2]   Challenges for vaccination in the elderly [J].
Aspinall R. ;
Del Giudice G. ;
Effros R.B. ;
Grubeck-Loebenstein B. ;
Sambhara S. .
Immunity & Ageing, 4 (1)
[3]   Antibody-based protection against HIV infection by vectored immunoprophylaxis [J].
Balazs, Alejandro B. ;
Chen, Joyce ;
Hong, Christin M. ;
Rao, Dinesh S. ;
Yang, Lili ;
Baltimore, David .
NATURE, 2012, 481 (7379) :81-U88
[4]   Permissive Secondary Mutations Enable the Evolution of Influenza Oseltamivir Resistance [J].
Bloom, Jesse D. ;
Gong, Lizhi Ian ;
Baltimore, David .
SCIENCE, 2010, 328 (5983) :1272-1275
[5]   Trial of 2009 Influenza A (H1N1) Monovalent MF59-Adjuvanted Vaccine. [J].
Clark, Tristan W. ;
Pareek, Manish ;
Hoschler, Katja ;
Dillon, Helen ;
Nicholson, Karl G. ;
Groth, Nicola ;
Stephenson, Iain .
NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (25) :2424-2435
[6]   Vaccine production capacity for seasonal and pandemic (H1N1) 2009 influenza [J].
Collin, Nicolas ;
de Radigues, Xavier .
VACCINE, 2009, 27 (38) :5184-5186
[7]   A Neutralizing Antibody Selected from Plasma Cells That Binds to Group 1 and Group 2 Influenza A Hemagglutinins [J].
Corti, Davide ;
Voss, Jarrod ;
Gamblin, Steven J. ;
Codoni, Giosiana ;
Macagno, Annalisa ;
Jarrossay, David ;
Vachieri, Sebastien G. ;
Pinna, Debora ;
Minola, Andrea ;
Vanzetta, Fabrizia ;
Silacci, Chiara ;
Fernandez-Rodriguez, Blanca M. ;
Agatic, Gloria ;
Bianchi, Siro ;
Giacchetto-Sasselli, Isabella ;
Calder, Lesley ;
Sallusto, Federica ;
Collins, Patrick ;
Haire, Lesley F. ;
Temperton, Nigel ;
Langedijk, Johannes P. M. ;
Skehel, John J. ;
Lanzavecchia, Antonio .
SCIENCE, 2011, 333 (6044) :850-856
[8]   Development of formulations that enhance physical stability of viral vectors for gene therapy [J].
Croyle, MA ;
Cheng, X ;
Wilson, JM .
GENE THERAPY, 2001, 8 (17) :1281-1290
[9]   Highly Conserved Protective Epitopes on Influenza B Viruses [J].
Dreyfus, Cyrille ;
Laursen, Nick S. ;
Kwaks, Ted ;
Zuijdgeest, David ;
Khayat, Reza ;
Ekiert, Damian C. ;
Lee, Jeong Hyun ;
Metlagel, Zoltan ;
Bujny, Miriam V. ;
Jongeneelen, Mandy ;
van der Vlugt, Remko ;
Lamrani, Mohammed ;
Korse, Hans J. W. M. ;
Geelen, Eric ;
Sahin, Ozcan ;
Sieuwerts, Martijn ;
Brakenhoff, Just P. J. ;
Vogels, Ronald ;
Li, Olive T. W. ;
Poon, Leo L. M. ;
Peiris, Malik ;
Koudstaal, Wouter ;
Ward, Andrew B. ;
Wilson, Ian A. ;
Goudsmit, Jaap ;
Friesen, Robert H. E. .
SCIENCE, 2012, 337 (6100) :1343-1348
[10]   Antibody Recognition of a Highly Conserved Influenza Virus Epitope [J].
Ekiert, Damian C. ;
Bhabha, Gira ;
Elsliger, Marc-Andre ;
Friesen, Robert H. E. ;
Jongeneelen, Mandy ;
Throsby, Mark ;
Goudsmit, Jaap ;
Wilson, Ian A. .
SCIENCE, 2009, 324 (5924) :246-251