Natural variation of poliovirus neutralization epitopes

Abstract

Poliovirus-neutralizing monoclonal antibodies were prepared against type 1, type 2, and type 3 wild laboratory (Mahoney, MEF1, and Saukett) and Sabin vaccine strains. Fifty-five poliovirus laboratory strains and field isolates were assayed by neutralization index test with a panel of homotypic monoclonal antibodies. A total of 27 monoclonal antibodies were used. Two categories of neutralization epitopes were found, i.e., cross-reacting (K), which is present on almost all strains of the same serotype, and strain-specific (V, variable), either wild (VW) or Sabin (VS). Several distinct neutralization epitopes were defined for each of the three poliovirus serotypes in almost every category. The study of antigenic variation of the Sabin type 1 vaccine virus during replication in human intestine showed that the VS neutralization epitope may be lost and even replaced by the VW epitopes of the parental Mahoney virus. A late isolate from a vaccine-fed infant recovered the complete neutralization epitope pattern of the Mahoney strain. Upon in vivo virus replication, a different kind of antigenic variation was also detected in which an epitope lost its function in virus neutralization but kept its antigenic conformation unaltered. Neutralization epitope analysis demonstrated that the presence of VS epitopes on a field isolate suggests the Sabin origin of the strain when the isolate displays the same epitope pattern as the original Sabin virus, or confirms it when the VS epitope(s) is mutually exclusive of VW epitopes. The lack of VS epitopes on a field isolate does not rule out its being of Sabin origin.

The antiviral activity of antibodies in vitro and in vivo

“…The data suggest that the attachment of 4-7 antibody molecules is required for the neutralization of picornaviruses of poliovirus/HRV dimensions. Studies by Horaud and colleagues (Blondel et al, 1986;Crainic et al, 1983;Diamond et al, 1985) have suggested that antibodies may bind to poliovirus without neutralization. This conclusion was made on the basis of studies using neutralizing antibodies which were analyzed for their activity (neutralization and binding) against a range of antigenic poliovirus variants (distinct serotypes and escape mutants).…”

Characterization of an Echovirus Type 30 Variant Isolated from Patients with Aseptic Meningitis

“…Thus, with respect to the prime phenomenon these two strains seemingly have an inverse relationship to each other. From the results of neutralization tests with crossabsorbed immune sera (Table 3), together with the general concept that enteroviruses have several neutralizing epitopes in the capsid proteins (3,8), we suggest that the Fukui strain has acquired a new antigenic determinant (s) but lacks one of the specific antigens present on the Bastianni strain. It is not clear whether the antigenic site(s) detected only in the Fukui 609/83 strain is a newly added structure independent of the original type-specific antigens or a derivative of the conformationally altered original epitopes.…”

Isolation and preliminary characterization of antigenic variant of echovirus type 11

“…The Fukui 212181 strain has acquired a new antigenic determinant(s) but lacks one of the specific antigens present on the Gregory strain. This finding suggests that several neutralizing epitopes might be present in the capsid proteins as in poliovirus [Crainic et al, 1983;Evans et al, 19831. It is not clear whether the antigenic site(s) detected only in the Fukui 212181 strain is a newly added structure independent of the original type specific antigens or a derivative of the conformationally altered original epitopes.…”