Accession Number:

ADA276158

Title:

Development of Safe, Effective Vaccines for Dengue Virus Disease by Recombinant Baculovirus

Descriptive Note:

Final rept. 1 Mar 1990-28 Feb 1993

Corporate Author:

NATIONAL INSTITUTES OF HEALTH BETHESDA MD

Report Date:

1993-06-30

Pagination or Media Count:

36.0

Abstract:

Baculovirus recombinants that separately express the full-length E or NS1 glycoprotein of DEN4 or DEN2 or the full-length E of DEN3 were constructed. Recombinants expressing C-terminally truncated 80E of the above three dengue serotype viruses were also constructed because earlier studies of recombinant vaccinia virus showed that this truncated 80 E is secreted extracellularly and is more immunogenic than the full-length E. The immunogenicity of baculovirus- expressed dengue virus Es was evaluated using the mouse dengue encephalitis model. Although the data for mouse protection would be more convincing were the mortality of negative control mice higher, sero-analysis provided evidence that the extracellular 80E elicited higher antibody response than did the intracellular E or the full-length E. We were encouraged by this re-suit and decided to test DEN4 80 E in a monkey experiment, to see if we could obtain a convincing protective response. The result showed that monkeys immunized with secreted 80 E developed low titers of neutralizing antibodies. Tests for post-challenge viremia failed to demonstrate viremia for reasons unclear at present. Analysis of sera indicated that all monkeys immunized with DEN4 Es were primed for a secondary antibody response to dengue virus challenge. This priming effect may be utilized in a two-phase vaccination strategy in which immunization with baculovirus-expressed E is followed by infection with a recombinant vaccinia virus or an under-attenuated live dengue vaccine in the second phase. RAI, Dengue, Baculovirus, Genetic engineering, Recombinant DNA, Glycoproteins, Vaccine development.

Subject Categories:

  • Medicine and Medical Research
  • Microbiology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE