Recombinant vaccinia viruses co-expressing dengue-1 glycoproteins prM and E induce neutralizing antibodies in mice

Four recombinant vaccinia viruses expressing different portions of the dengue type 1 virus (DEN-1) genome (C-prM-E-NS1-NS2A-NS2B; prM-E; prM-E-NS1-NS2A-NS2B; or NS1-NS2A) were constructed in order to establish the most immunogenic configuration of DEN-1 proteins. Both recombinants producing prM and E in the absence of C induced the synthesis of extracellular forms of E in vitro. Mice inoculated with these two recombinants produced DEN-1 neutralizing (NEUT) and haemagglutination inhibiting (HAI) antibodies. The other two recombinant vaccinia viruses, which did not induce the production of extracellular forms of E, did not induce E-specific immune responses. These results support our previous studies on the design of flavivirus-vaccinia vaccine candidates by showing the importance of co-expressing prM and E in order to induce the synthesis of extracellular E and to elicit NEUT and HAI antibodies.