Characterization of antibody responses to combinations of a dengue virus type 2 DNA vaccine and two dengue virus type 2 protein vaccines in rhesus macaques

J Virol. 2006 Oct;80(19):9577-85. doi: 10.1128/JVI.00284-06.

Abstract

We evaluated three nonreplicating dengue virus type 2 (DENV-2) vaccines: (i) a DNA vaccine containing the prM-E gene region (D), (ii) a recombinant subunit protein vaccine containing the B domain (i.e., domain III) of the E protein as a fusion with the Escherichia coli maltose-binding protein (R), and (iii) a purified inactivated virus vaccine (P). Groups of four rhesus macaques each were primed once and boosted twice using seven different vaccination regimens. After primary vaccination, enzyme-linked immunosorbent assay (ELISA) antibody levels increased most rapidly for groups inoculated with the P and DP combination, and by 1 month after the second boost, ELISA titers were similar for all groups. The highest plaque reduction neutralization test (PRNT) titers were seen in those groups that received the DR/DR/DR combination (geometric mean titer [GMT], 510), the P/P/P vaccine (GMT, 345), the DP/DP/DP combination (GMT, 287), and the R/R/R vaccine (GMT, 200). The next highest titers were seen in animals that received the D/R/R vaccine (GMT, 186) and the D/P/P vaccine (GMT, 163). Animals that received the D/D/D vaccine had the lowest neutralizing antibody titer (GMT, 49). Both ELISA and PRNT titers declined at variable rates. The only significant protection from viremia was observed in the P-vaccinated animals (mean of 0.5 days), which also showed the highest antibody concentration, including antibodies to NS1, and highest antibody avidity at the time of challenge.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Viral / immunology*
  • Antibodies, Viral / pharmacology
  • Antibody Affinity / immunology
  • Chlorocebus aethiops
  • Dengue Virus / classification
  • Dengue Virus / immunology*
  • Immunologic Memory / immunology
  • Macaca mulatta
  • Vaccines, DNA / immunology*
  • Vero Cells
  • Viral Proteins / immunology*
  • Viral Vaccines / immunology*
  • Viremia / immunology
  • Viremia / prevention & control
  • Viremia / virology

Substances

  • Antibodies, Viral
  • Vaccines, DNA
  • Viral Proteins
  • Viral Vaccines