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Journal of Virology, October 2006, p. 9577-9585, Vol. 80, No. 19
0022-538X/06/$08.00+0     doi:10.1128/JVI.00284-06

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

Monika Simmons,1* Kevin R. Porter,1,2 Curtis G. Hayes,1 David W. Vaughn,3 and Robert Putnak3

Viral Diseases Department, Naval Medical Research Center, Silver Spring, Maryland,1 Department of Medicine, Uniformed Services University of Health Sciences, Bethesda, Maryland,2 Department of Virus Diseases, Walter Reed Army Institute of Research, Silver Spring, Maryland3

Received 8 February 2006/ Accepted 10 July 2006

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.

* Corresponding author. Mailing address: Viral Diseases Department, Naval Medical Research Center, Silver Spring, MD 20910-7500. Phone: (301) 319-7447. Fax: (301) 319-7451. E-mail: simmonsm{at}nmrc.navy.mil.

Journal of Virology, October 2006, p. 9577-9585, Vol. 80, No. 19
0022-538X/06/$08.00+0     doi:10.1128/JVI.00284-06




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