Expression of immunomodulating molecules by recombinant viruses: Can the immunogenicity of live virus vaccines be improved?

Several obstacles exist for the development and use of live attenuated vaccines, including difficulty in achieving a proper balance between attenuation of viral replication and immunogenicity; inducing a strong T-helper 1 response in early life when the immune system is T helper 2 biased and immunization is sometimes associated with immunopathology and the immunosuppressive effect of maternal antibodies in infants. For some viral infections, the immune response to natural infection does not confer solid protection, complicating the task of vaccine development. The development of methods for generation of recombinant viruses provided new opportunities for improving the immunogenicity of live virus vaccine candidates, including the construction of viruses that express cytokines or other immunomodulating molecules. Depending on the choice of immunomodulating molecule, various stages of the immune response can be affected, such as antigen presentation or T-cell proliferation and differentiation. In addition to using the approach for development of viral live attenuated vaccines, it is currently being explored for the development of antitumor vaccines. For this type of vaccine, expression of tumor antigens and one or more immunomodulating molecules by one or several recombinant viruses has been proposed.