Broad protection against influenza infection by vectored immunoprophylaxis in mice

• Published in: Nature biotechnology Vol. 31; no. 7; pp. 647 - 652
• Main Authors: Balazs, Alejandro B, Bloom, Jesse D, Hong, Christin M, Rao, Dinesh S, Baltimore, David
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.07.2013; Nature Publishing Group
• Subjects: 631/326/596/2561; 631/61/24/590; 692/699/255/1578; 692/700/459; Adeno-associated virus; Agriculture; Animals; Antibodies; Antibodies, Neutralizing - administration & dosage; Antigenic determinants; Antigens; Bioinformatics; Biomedical Engineering/Biotechnology; Biomedicine; Biotechnology; Dependovirus - genetics; Diseases; Elderly; Elderly patients; Epitopes - genetics; Epitopes - immunology; Genetic Vectors; Health aspects; Humans; Immunization; Immunology; Infection; Inflammation; Influenza; Influenza A Virus, H1N1 Subtype - genetics; Influenza A Virus, H1N1 Subtype - immunology; Influenza A Virus, H1N1 Subtype - pathogenicity; Influenza Vaccines - administration & dosage; Influenza Vaccines - genetics; Influenza virus; Influenza viruses; Influenza, Human - genetics; Influenza, Human - pathology; Influenza, Human - prevention & control; Influenza, Human - virology; Injection; letter; Life Sciences; Mice; Monoclonal antibodies; Prevention; Rodents; Swine influenza; Vaccines; Weight loss; United States; California
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/nbt.2618

Gene therapy encoding a single influenza broadly neutralizing antibody durably protects even immunocompromised mice from illness caused by diverse influenza strains. 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.