Mutations have been identified in variants of poliovirus, type 1 (Mahoney) on the basis of their resistance to neutralization by individual monoclonal antibodies. The phenotypes of these variants were defined in terms of antibody binding; the pattern of epitopes expressed or able to be exploited for neutralization were complex. Single amino acid changes can have distant (in terms of linear sequence) and generalized effects on the antigenic structure of poliovirus and similarly constituted virions.
"This method combines medium-resolution 3D maps of complexes between PV type 2 (PV2) and monoclonal antibody fragments obtained from cryo-electron microscopy (cryoEM) images and known structure of the PV2 at high resolution determined using X-ray crystallography. This structural information is complementary to the data obtained by analysis of antigenic mutants (Blondel et al., 1986; Diamond et al., 1985; Minor et al., 1983, 1985; Page et al., 1988), chimera (Minor et al., 1991) and escape mutants (Ketterlinus et al., 1993; Minor et al., 1986; Wiegers et al., 1988), which have been used to map the viral antigenic sites. These combined studies could be used as a guide in order to select antibodies able to map the entire " epitopic " surface of the virus. "
"Analyzing the footprint of each Fab on the three-dimensional structure of the viral capsid helps to map in 3D and in detail the precise amino acids and the epitope site required for the binding of the antibodies studied here. This structural information is complementary to the data obtained by analysis of antigenic mutants (Blondel et al., 1986; Diamond et al., 1985; Minor et al., 1983, 1985; Page et al., 1988), chimera (Minor et al., 1991) and escape mutants (Ketterlinus et al., 1993; Minor et al., 1986; Wiegers et al., 1988), which have been used to map the viral antigenic sites. These combined studies could be used as a guide in order to select antibodies able to map the entire " epitopic " surface of the virus. "
[Show abstract][Hide abstract] ABSTRACT: The inactivated polio vaccine (IPV) contains poliovirus (PVs) samples that belong to serotypes 1, 2 and 3. All three serotypes contain the D-antigen, which induces protective antibodies. The antigenic structure of PVs consists of at least four different antigenic sites and the D-antigen content represents the combined activity of multiple epitopes (Ferguson et al., 1993; Minor, 1990; Minor et al., 1986). The potency of IPV vaccines is determined by measuring the D-antigen content. Several ELISA methods have been developed using polyclonal or monoclonal antibodies (Mabs) in order to quantify the D-antigen content. Characterization of the epitopes recognized by the different Mabs is crucial to map the entire virus surface and ensure the presence of epitopes able to induce neutralizing antibodies. In a new approach, combining cryo-electron microscopy and image analysis with X-ray crystallography data available along with identification of exposed amino acids we have mapped in 3D the epitope sites recognized by five specific Fabs and one Mab and characterized precisely the antigenic sites for these Mabs. We propose this method to be used to map the entire “epitopic” surface of virus.
"In fact, we presently generated MAbs by parenteral immunization of adult mice which are not expected to permit an extensive replication of CAV9 as in the course of natural infection. Although the procedure we used has been widely reported for other viruses (Blondel et al., 1986; Diamond et al., 1985; Greenberg et al., 1983; Minor et al., 1986; Page et al., 1988), it is possible that a different route of uptake and processing of the virus may lead to a different epitope targeting by the immune system. Further work is therefore needed to address this issue. "
[Show abstract][Hide abstract] ABSTRACT: A panel of murine IgG monoclonal antibodies (MAbs) was produced against coxsackievirus A9 (CAV9). Fifty-nine MAbs reactive in ELISA with purified CAV9 were identified. Eighteen of them could efficiently inhibit infection by CAV9 but not coxsackieviruses B. Neutralization-resistant CAV9 variants to four different MAbs were isolated and tested for resistance to neutralization by other MAbs of the panel. Three groups of reactivity including 10, 7, and 1 MAbs were thus identified. Sequencing of neutralization-escape virus mutants showed that neutralization by one MAb group was affected by change of VP3 amino acids 62 or 69. For the second group of reactivity, mutations included amino acids 154 or 165 of VP2. The only MAb of the third group selected for a change at residue 70 of VP2. Protection studies in a newborn mouse model of myositis suggested that either epitopes in VP2 or in VP3 mediate protection from CAV9 infection in vivo.
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