Progress toward vaccines against viruses that cause heart disease

Of the numerous viruses that have been implicated as causes of viral inflam matory cardiomyopathy, only the 6 serotypes of the group B coxsackieviruses (CVB 1-6) and adenovirus type 2 (Ad 2) have been regularly linked to heart disease on the ba sis of both clinical investigations as well as animal mo dels (in the case of the coxsackieviruses). Of these, only the coxsackievir uses offer a truly well-characterized system for not only investigations us ing a small animal disease model (myocarditis in mice) but for studies of t he virus at the molecular level and in cell culture systems. The pending wo rldwide eradication of the related enteroviruses, the polioviruses, will fu rther emphasize the importance of the coxsackieviruses in years to come. St udies using poliovirus have shown that enteroviruses can be attenuated for disease to create highly successful and safe hu-man vaccines. Furthermore, using recombinant DNA approaches, strains of polioviruses have been created that demonstrate a human enterovirus can express small proteins as well as foreign antigenic epitopes, thus creating multivalent chimeric vaccine str ains of virus. Our laboratory has been exploring coxsackievirus 3-based vec tors as models for both multivalent chimeric vaccines as well as expression vectors. The coxsackievirus can be successfully attenuated using both poin t mutations as well as chimeric genome technology. The coxsackievirus can a lso express intact small proteins in biologically active form as well as an tigenic epitopes. Although it is doubtful that the marketplace will support the development of antiviral vaccines to combat human heart disease at pre sent, the technology exists to make such vaccines a reality.