New strategies for immune-mediated anti-viral drug and vaccine development

Substantial progress in the development of new anti-viral drugs has taken place in recent years. Most of these new drugs belong to three groups of compounds, nucleoside analogs, thymidine kinase-dependent nucleotide analogs and specific viral enzyme inhibitors. Although these drugs revolutionized the treatment of several viral diseases, the involvement of the immune system is crucial for complete recovery and prevention of re-infection. New advances in the understanding of immune regulation mechanisms, mainly the role of cytokines, led to the development of several new immunologically-based anti-viral drugs and treatments. The most studied group of immunomodulators is the cytokines, some of which were shown to act as potent stimulators of immune responses. Other, non-cytokine immune modulators have also been successfully employed in both humans and experimental animals as anti-viral drugs of which several are currently in clinical trials. Advances in genetic engineering and transgenic mouse technologies facilitated the production of humanized as well as authentic human anti-viral monoclonal antibodies. Some of these antibodies proved to be clinically efficacious and are commercially produced as anti-viral drugs. As is often the case in anti-viral treatments, a combination of conventional and an immune-mediated anti-viral drugs or a combination therapy involving immunomodulators, therapeutic vaccines, immune intervention and even gene therapy might prove most efficacious as a treatment for a particular virus. Most of the advances made in anti-viral treatments have also been applied to the development of new vaccines. Some of the classical attenuated viruses are being replaced by recombinant attenuated viruses. Recombinant viral vaccines containing genes encoding other viral antigens and/or cytokines are being tested as new vaccines. Several chimeric viral vaccines have proven efficacious in experimental animals and are now in different phases of clinical trials. This review will encompass the major new developments in this field, including some that have not yet been subjected to human trials.