Mechanisms of neutralizing antibody response probed using synthetic virus-like structures

Class-switched neutralizing antibody production is rapidly induced upon many viral infections and often long-lived, but the underlying mechanisms remain incompletely understood. Here we show that several features of this antibody response can be reconstituted by synthetic virus-like structures containing minimal, highly purified biochemical ingredients commonly found in enveloped viruses, and without viral replication or any other adjuvants. These findings reveal a shared mechanism for the production of neutralizing antibodies upon viral infection. High epitope density is capable but not necessary for driving antibody secretion. Instead, even a few molecules of surface antigen, when combined with nucleic acids within these structures, can trigger strong antiviral IgG production. As a result, B cells integrate both signals from individual viral particulate antigens to initiate a neutralizing IgG response. ### Competing Interest Statement W. Cheng has a patent pending on SVLS. B. Chackerian has equity in Flagship Laboratories 72. J. Zikherman is on the scientific advisory board for Walking Fish Therapeutics. No other disclosures were reported.