Synergistic neutralizing activities of antibodies to outer membrane proteins of the two infectious forms of vaccinia virus in the presence of complement.

The two forms of infectious vaccinia virus particles, known as intracellular mature virions and extracellular enveloped virions, are liberated by cell lysis and exocytosis, respectively. The extracellular enveloped form, which is highly resistant to antibody neutralization, contains an outer membrane surrounding an intracellular mature form. We provide evidence that complement mediates antibody-dependent lysis of the outer membrane of extracellular virus, exposing the inner infectious virus to neutralization by a second antibody. These results can help explain the disparity between the in vitro neutralizing and in vivo protective effects of antibodies to extracellular envelope proteins as well as the enhanced protection afforded by specific combinations of antibodies.