Evaluation of the protective efficacy of a recombinant dengue envelope B domain fusion protein against dengue 2 virus infection in mice.
A recombinant protein containing part of the dengue (DEN) 2 envelope protein was evaluated as a subunit immunogen for vaccination against DEN virus infection. A gene fragment encoding amino acids 298-400 (B domain) of the DEN-2 virus envelope was expressed as a fusion protein with the maltose binding protein (MBP) of Escherichia coli. This recombinant, DEN-2(B)/MBP, was purified and analyzed for its antigenicity, immunogenicity, and ability to protect mice against lethal challenge. The recombinant antigen reacted with a DEN-2 type-specific neutralizing monoclonal antibody (3H5), DEN-2 hyperimmune mouse ascitic fluid, and DEN-2 immune human sera. When administered to mice, DEN-2(B)/MBP elicited a DEN-2 virus neutralizing antibody response that conferred partial protection against challenge infection with a lethal dose of DEN-2 virus administered by intracranial inoculation. In addition, no replication of DEN-2 virus was detectable in the brains of the immunized mice as compared with control mice that were killed six days after challenge. Sera from immunized mice revealed no cross-neutralizing antibody to any of the other DEN serotypes in the plaque-reduction neutralization test. These findings warrant further studies with the DEN-2(B)/MBP antigen as a potential human vaccine candidate. An effective vaccine could prevent thousands of cases of illness and many deaths each year resulting from DEN virus infections.
Simmons
M
M
Naval Medical Research Institute, Bethesda, Maryland 20889-5607, USA.
Nelson
W M
WM
Wu
S J
SJ
Hayes
C G
CG
D018528:ATP-Binding Cassette Transporters; D000818:Animals; D002352:Carrier Proteins / Q000276:immunology*; D003715:Dengue / Q000276:immunology / Q000517:prevention & control*; D003716:Dengue Virus / Q000276:immunology*; D004195:Disease Models, Animal; D029968:Escherichia coli Proteins; D005260:Female; D015686:Gene Products, env / Q000276:immunology* / Q000494:pharmacology; D058619:Maltose-Binding Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009004:Monosaccharide Transport Proteins; D011993:Recombinant Fusion Proteins / Q000276:immunology* / Q000494:pharmacology; D016019:Survival Analysis
D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D015686:Gene Products, env; D058619:Maltose-Binding Proteins; D009004:Monosaccharide Transport Proteins; D011993:Recombinant Fusion Proteins; C461599:maltose transport system, E coli