DNA vaccines for HFRS: Laboratory and clinical studies

Abstract

DNA vaccines can be constructed to produce specific immunogens while avoiding the risks associated with propagating infectious viruses. Plasmid DNA vaccines have well established manufacturing procedures and are safe in that they are replication defective, cannot revert to virulence and cannot be transmitted from person-to-person or into the environment. In addition, DNA vaccines can be combined to form multivalent formulations and can be delivered by a variety of methods. Because of these numerous advantages, we have developed DNA vaccines expressing the envelope glycoprotein genes of hantaviruses causing hemorrhagic fever with renal syndrome (HFRS). We have demonstrated that these DNA vaccines elicit neutralizing antibodies in multiple laboratory animal species when delivered to skin or muscle tissues. Moreover, these vaccines delivered as active vaccines or passive vaccines (e.g., transfer of sera from vaccinated rabbits or nonhuman primates), protected hamsters from infection with HFRS-causing hantaviruses. Early clinical studies of HFRS vaccines expressing Hantaan virus or Puumala virus genes have been completed and show promise for further development. Despite these advantages, issues relating to inconsistent immunogenicity and immune interference remain to be addressed.