Antibody-Based Strategies to Prevent and Treat Influenza

Passive immunization using antibodies is a promising alternative to other antiviral treatment options. The potential for seasonal protection arising from a single injection of antibodies is appealing and has been pursued for a number of infectious agents. However, until recently, antibody-based strategies to combat infectious agents have been hampered due to the fact that most antibodies have been found to be strain specific, with the virus evolving resistance in many cases. The discovery of broadly neutralizing antibodies (bNAbs) in influenza, dengue virus, and HIV, which bind to multiple, structurally diverse strains, has provided renewed interest in this area. This review will focus on new technologies that enable the discovery of bNAbs, the challenges and opportunities of immunotherapies as an important addition to existing antiviral therapy, and the role of antibody discovery in informing rational vaccine discovery – with agents targeting influenza specifically addressed. Multiple candidates have entered the clinic and raise the possibility that a single antibody or small combination of antibodies can effectively neutralize a wide variety of strains. However, challenges remain – including combating escape variants, pharmacodynamics of antibody distribution, and development of efficacy biomarkers beyond virologic endpoints.National Institutes of Health (U.S.) (Award 1R01AI111395)National Institutes of Health (U.S.) (Merit Award R37 GM057073-13)Singapore. National Research Foundation (Singapore-MIT Alliance for Research and Technology