Non-neutralizing monoclonal antibodies can prevent lethal alphavirus encephalitis

Abstract

Among the heterogeneous population of antibodies specifically induced during many acute viral infections, those having virus-neutralizing activity in vitro are generally considered to be most important for recovery and immunity to reinfection. Similarly, the ability to stimulate production of circulating neutralizing (NT) antibodies is a major criterion for evaluating the immunoprophylactic potential of many antiviral vaccines¹. Although there is obviously an association between NT antibody induction and host resistance, we present here data which indicate that other virus-specific antibodies lacking NT function may be equally important in conferring protective immunity to alphaviruses. We used monoclonal antibodies against Sindbis virus (SV) to demonstrate that passive protection of SV-infected mice from fatal paralytic central nervous system (CNS) disease may be mediated not only by antibodies which neutralize the infectivity of extracellular virus particles but also by those lacking this capacity, which react preferentially with virus-infected cells.