High frequency of antigenic variants among naturally occurring human Coxsackie B4 virus isolates identified by monoclonal antibodies

The Coxsackie B virus group consists of six serotypes (B1–B6) that are antigenically distinct. In patients, the Coxsackie B4 serotype can produce a variety of clinical diseases (for example, pleurodynia, respiratory illness, meningitis, myocarditis, orchitis and diabetes)1,2. It is not known, however, whether the different clinical diseases are due to chance infection of particular organs by Coxsackie B4 or due to antigenic variants of Coxsackie B4 that are inherently different in their tissue tropism. The long-standing reference hyperimmune sera do not identify variants that may exist within each of the serotypes3. In an attempt to identify variants of the Coxsackie B4 serotype, we prepared a panel of 18 monoclonal antibodies that neutralized the prototype Coxsackie B4 strain. These monoclonal antibodies have been characterized as to their subclass, neutralization titres and reactivity patterns with recent clinical isolates. Here we have identified over 13 variants of CoxsacKie B4 virus and have shown that there are major antigenic differences among naturally occurring isolates. Using monoclonal antibodies as a selecting agent, we find that the frequency of antigenic mutation may be as high as 10−4.