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.
Fonseca
B A
BA
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06510.
Pincus
S
S
Shope
R E
RE
Paoletti
E
E
Mason
P W
PW
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D003715:Dengue / Q000276:immunology / Q000517:prevention & control; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology*; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D006367:HeLa Cells; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D051379:Mice; D009500:Neutralization Tests; D011499:Protein Processing, Post-Translational; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics* / Q000276:immunology; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D006023:Glycoproteins; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D014765:Viral Vaccines; C072281:E protein TH Sman, Dengue virus