DENGUE-1 VIRUS ENVELOPE GLYCOPROTEIN GENE EXPRESSED IN RECOMBINANT BACULOVIRUS ELICITS VIRUS-NEUTRALIZING ANTIBODY IN MICE AND PROTECTS THEM FROM VIRUS CHALLENGE

In order to test the feasibility of baculovirus (Autographa californica nuclear polyhedrosis virus, AcNPV) expression vectors for making immunogens against dengue-1 (DEN-1) virus, a portion of the envelope (E) glycoprotein gene of DEN-1 virus was cloned and expressed. The recombinant baculovirus contains 107 nucleotides from the 3' terminus of the DEN-1 matrix (M) gene, which encodes a hydrophobic signal peptide and extends through the first 1, 245 nucleotides of E, terminating 243 nucleotides before the 3' terminus of E. When the recombinant virus was grown in Spodoptera frugiperda cells, about 1 mg of E antigen was made per 10(9) cells. Recombinant E antigen reacted with E protein-specific monoclonal antibodies and stimulated production of DEN-1 virus neutralizing antibody in BALB/c mice. Mice immunized with recombinant E antigen or with heat-inactivated DEN-1 virus were protected significantly against lethal DEN-1 virus challenge. A dose/response effect was observed, with increasing amounts of recombinant antigen leading to increased survival. These results demonstrate the utility of baculovirus for producing immunogens against DEN-1 virus.