DNA vaccination with vaccinia virus L1R and A33R genes protects mice against a lethal poxvirus challenge

Previously we found that passive transfer of monoclonal antibodies (MAbs) s pecific to either the vaccinia virus (VACV) L1R or A33R gene product protec ted mice from challenge with VACV, The L1R-specific MAbs, which bind the in tracellular mature virion (IMV), neutralized virus in cell culture, whereas the A33R-specific MAbs, which bind extracellular enveloped virions (EEV), did not. To investigate whether a protective response could be generated by vaccination with these genes, we constructed and evaluated DNA vaccines ex pressing the VACV L1R and/or A33R genes under control of a cytomegalovirus promoter. Mice were vaccinated with DNA-coated gold beads by using a gene g un and then challenged with VACV (strain WR) intraperitoneally. Mice vaccin ated with L1R alone developed neutralizing antibodies and were partially pr otected. Mice vaccinated with a combination of both genes loaded on the sam e gold beads developed a robust anti-A33R response; however, no neutralizin g antibody response was detected, and the mice were not protected. In contr ast, when mice were vaccinated with L1R and A33R loaded on different gold b eads, neutralizing (presumably anti-L1R) and anti-A33R antibody responses w ere detected, and protection was markedly improved. Our results indicated t hat vaccination with both L1R and A33R proteins, intended to evoke mechanis tically distinct and complementary forms of protection, was more effective than vaccination with either protein by itself. (C) 2000 Academic Press.