Vaccine candidates for dengue virus type 1 (DEN1) generated by replacement of the structural genes of rDEN4 and rDEN4Δ30 with those of DEN1

Abstract

Background: Antigenic chimeric viruses have previously been generated in which the structural genes of recombinant dengue virus type 4 (rDEN4) have been replaced with those derived from DEN2 or DEN3. Two vaccine candidates were identified, rDEN2/4Δ30(ME) and rDEN3/4Δ30(ME), which contain the membrane (M) precursor and envelope (E) genes of DEN2 and DEN3, respectively, and a 30 nucleotide deletion (Δ30) in the 3' untranslated region of the DEN4 backbone. Based on the promising preclinical phenotypes of these viruses and the safety and immunogenicity of rDEN2/4Δ30(ME) in humans, we now describe the generation of a panel of four antigenic chimeric DEN4 viruses using either the capsid (C), M, and E (CME) or ME structural genes of DEN1 Puerto Rico/94 strain.

An Adjuvanted, Tetravalent Dengue Virus Purified Inactivated Vaccine Candidate Induces Long-Lasting and Protective Antibody Responses Against Dengue Challenge in Rhesus Macaques

“…Serum samples were obtained before each dose (days 0 and 28) and at 4, 12, 20, 32, 36, 40, and 44 weeks post-dose 2 (days 56, 112, 168, 252, 280, 308, and 336). Five animals from each group were randomly selected to be challenged with DENV-2 strain S16803 39 (passaged four times in Vero cells) on day 252 or DENV-1 strain Puerto Rico/94 (PR/94 40 ; passaged two times in Vero cells) on day 308. Dengue serotype-specific NAb titers were determined from sera obtained at all time points up to and including day 168 ( N = 10 per group) and on days 252, 280, 308, and 336 ( N = 5 per group).…”

Dengue in Cape Verde: Vector Control and Vaccination

“…No commercially available clinical cure or vaccine is currently available for dengue, but efforts are to develop one (Blaney et al, 2007;Hombach et al, 2007). Effective vaccines have been produced against other flavivirus diseases such as yellow fever, Japanese encephalitis, and tick-borne encephalitis, so there is good hope for a vaccine for dengue.…”

Targeted Mutagenesis as a Rational Approach to Dengue Virus Vaccine Development

“…First, reverse genetics has been used to introduce the structurally conserved attenuating Δ30 mutation into the 3′-UTR of cDNA clones of DENV-1, DENV-2 and DENV-3 (Blaney et al 2004a, b, 2005; Durbin et al 2006a; Whitehead et al 2003a). Alternatively, antigenic chimeric viruses have been generated by replacement of the structural proteins of the attenuated rDEN4Δ30 vaccine candidate with those from DENV-1, DENV-2 or DENV-3 (Blaney et al 2004a; 2007, Durbin et al 2006b; Whitehead et al 2003b). Targeted mutagenesis of the DENV-3 3′-UTR has also been used to identify additional attenuated vaccine candidates for this serotype (Blaney et al 2008).…”