The neutralization (N) site on the gp56 (E2)
surface glycoprotein of the TC-83
vaccine strain of
Venezuelan equine encephalomyelitis (VEE) virus has been characterized using
monoclonal antibodies. Five new
epitopes (E2d-h) were identified three of which could be mapped into the critical N site by using a competitive binding assay (CBA).
Antibodies reactive with these three
epitopes had either N or N and hemagglutination-inhibition activity. All
epitopes contained within this N site elicited
monoclonal antibodies that could protect mice from peripheral virus challenge.
Antibodies reactive with the N site on other subtypes of VEE virus (IC and II) bound to, but failed to neutralize, TC-83 virus.
Epitopes defined by these
antibodies could be located outside of the N site on TC-83 virus by CBA. Antigenic activity of all
epitopes except E2d was resistant to treatment with 2% SDS, 3% beta-
mercaptoethanol, or cleavage with Staphylococcus aureus V8
protease. Those
antibodies which defined
epitopes located within the N site of TC-83 with CBA bound the same V8 fragments in immunoblots. Those
antibodies which defined
epitopes not located within the N site bound a different set of fragments than
neutralizing antibodies. These results indicate that there is a specific N site on the E2 of VEE virus which undergoes significant antigenic drift while maintaining structural and functional integrity.