Characterization of the Recombinant Vaccinia Viruses Expressing the Lassa Virus Glycoprotein Genes.

Lassa virus (LV) is a member of the Arenaviridae family and categorized as a hazard group 4 virus by the Advisory Committee on Dangerous Pathogens. These viruses require maximum containment facilities for infectious virus studies. Consequently the virus and the disease have been very poorly researched. This study describes the construction and characterization of recombinant vaccinia viruses expressing LV glycoproteins prepared with two strains of vaccinia virus; Lister and Western Reserve. The LV genome encodes two glycoprotein genes, G1 and G2. Both glycoproteins have been expressed, identified and characterized as being authentic viral proteins using anti-LV human antisera and mouse monoclonal antibodies. To assess if the recombinant vaccinia viruses would protect animals from a lethal challenge of LV, guinea pigs were immunized with these recombinant vaccinia viruses, then challenged 56 days after vaccination with a lethal dose of LV. A recombinant vaccinia virus expressing the LV nucleoprotein, which had been shown to protect in previous studies, was included for comparison. Various parameters of LV infection were monitored for 35 days post challenge. Although the recombinant vaccinia viruses protected guinea pigs from the lethal LV challenge, examination of disease profiles in vaccinated and unvaccinated animals revealed that protected animals still had clinical evidence of LV disease. In the guinea pigs immunized with the recombinant vaccinia viruses, the effects of the disease were moderated in most animals surviving LV challenge. Weight loss, fever and haematological factors were mild to moderate in vaccinated animals. A correlation has been established in human patients with Lassa Fever between increased serum aspartate aminotransferase (AST) levels and a greater risk of death. The AST levels in these vaccinated guinea pigs remained at moderate levels, whereas the levels in the control guinea pigs were greatly increased