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Progress toward vaccines against viruses that cause heart disease
K Höfling1, K S Kim, J S Leser
1Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, USA.
Insights
Group B coxsackieviruses (CVB 1-6) are key models for viral heart disease research. These viruses can be engineered into safe, effective chimeric vaccines and expression vectors.
Area of Science:
- Virology
- Cardiology
- Vaccinology
Background:
- Viral inflammatory cardiomyopathy is linked to specific viruses, notably group B coxsackieviruses (CVB 1-6) and adenovirus type 2.
- Coxsackieviruses provide a well-characterized model for studying viral heart disease using animal models, molecular analysis, and cell cultures.
- The eradication of polioviruses highlights the significance of related enteroviruses, like coxsackieviruses, for future research and vaccine development.
Purpose of the Study:
- To explore coxsackievirus 3-based vectors as models for developing multivalent chimeric vaccines.
- To investigate the potential of coxsackievirus vectors for use as expression systems.
- To assess the feasibility of creating attenuated coxsackievirus strains for vaccine purposes.
Main Methods:
- Utilizing coxsackievirus 3 as a basis for vector development.
- Employing point mutations and chimeric genome technology to attenuate coxsackievirus.
- Investigating the expression of small proteins and foreign antigenic epitopes by engineered coxsackieviruses.
Main Results:
- Demonstrated successful attenuation of coxsackievirus using genetic modification techniques.
- Showcased the capability of coxsackievirus vectors to express intact, biologically active small proteins.
- Confirmed the expression of antigenic epitopes, indicating potential for chimeric vaccine development.
Conclusions:
- Coxsackievirus vectors represent a viable platform for creating multivalent chimeric vaccines and expression systems.
- The technology exists to develop antiviral vaccines targeting viral heart disease, despite current market limitations.
- Further research into coxsackievirus attenuation and expression holds promise for future vaccine strategies.
Abstract:
Of the numerous viruses that have been implicated as causes of viral inflammatory 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 basis of both clinical investigations as well as animal models (in the case of the coxsackieviruses). Of these, only the coxsackieviruses offer a truly well-characterized system for not only investigations using a small animal disease model (myocarditis in mice) but for studies of the virus at the molecular level and in cell culture systems. The pending worldwide eradication of the related enteroviruses, the polioviruses, will further emphasize the importance of the coxsackieviruses in years to come. Studies using poliovirus have shown that enteroviruses can be attenuated for disease to create highly successful and safe human 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 strains of virus. Our laboratory has been exploring coxsackievirus 3-based vectors as models for both multivalent chimeric vaccines as well as expression vectors. The coxsackievirus can be successfully attenuated using both point mutations as well as chimeric genome technology. The coxsackievirus can also express intact small proteins in biologically active form as well as antigenic epitopes. Although it is doubtful that the marketplace will support the development of antiviral vaccines to combat human heart disease at present, the technology exists to make such vaccines a reality.