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.
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.
Simmons
Monika
M
Viral Diseases Department, Naval Medical Research Center, Silver Spring, MD 20910-7500, USA. simmonsm@nmrc.navy.mil
Porter
Kevin R
KR
Hayes
Curtis G
CG
Vaughn
David W
DW
Putnak
Robert
R
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology* / Q000494:pharmacology; D000915:Antibody Affinity / Q000276:immunology; D002522:Chlorocebus aethiops; D003716:Dengue Virus / Q000145:classification / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology; D008253:Macaca mulatta; D019444:Vaccines, DNA / Q000276:immunology*; D014709:Vero Cells; D014764:Viral Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*; D014766:Viremia / Q000276:immunology / Q000517:prevention & control / Q000821:virology
D000914:Antibodies, Viral; D019444:Vaccines, DNA; D014764:Viral Proteins; D014765:Viral Vaccines