Topographical analysis of epitope relationships on the envelope glycoprotein of yellow fever 17D vaccine and the wild type Asibi parent virus.

Monoclonal antibodies (MCA), with defined molecular specificity, were used in a competition binding enzyme-linked immunosorbent assay (ELISA) to locate the relative positions of the epitopes on the envelope glycoprotein of yellow fever 17D vaccine virus and its wild type parent virus, Asibi (AS). Five topographically distinct antigenic domains were defined on the E glycoprotein of the 17D vaccine. Three of these (A, B, and C) were represented by one MCA each, a fourth (D) was represented by two MCA, and a fifth domain (E) comprised a major cluster of at least five overlapping epitopes. Asibi virus also possessed domain E which is proposed to be a conserved antigenic region within the envelope glycoprotein of all flaviviruses. Domains A and C were not represented on Asibi virus and one epitope, situated proximal to the E domain, showed structural alterations in physical overlap. Functional activities were assigned to physically mapped epitopes by haemagglutination inhibition (HAI), virus neutralisation (N), and passive protection in mice. The HAI and N functions were not necessarily linked but only MCA with N activity were able to protect mice passively against lethal infection. All domains demonstrated a heterogeneous range of biological properties dependent upon the virus strain rather than the epitope.