Immunogenicity and safety of a tetravalent dengue vaccine in healthy adults in India: A randomized, observer-blind, placebo-controlled phase II trial

Abstract

Dengue is a mosquito-borne viral disease that is endemic in India. We evaluated the immunogenicity and safety of recombinant, live-attenuated, tetravalent dengue vaccine (CYD-TDV) in Indian adults. In this observer-blind, randomized, placebo-controlled, Phase II study, adults aged 18-45 years were randomized 2:1 to receive CYD-TDV or placebo at 0, 6 and 12 months in sub-cutaneous administration. Immunogenicity was assessed using a 50% plaque reduction neutralization test (PRNT50) at baseline and 28 days after each study injection. 189 participants were enrolled (CYD-TDV [n = 128]; placebo, [n = 61]). At baseline, seropositivity rates for dengue serotypes 1, 2, 3 and 4 ranged from 77.0% to 86.9%. Seropositivity rates for each serotype increased after each CYD-TDV injection with a more pronounced increase after the first injection. In the CYD-TDV group, geometric mean titres (GMTs) were 2.38 to 6.11-fold higher after the third injection compared with baseline but remained similar to baseline in the placebo group. In the CYD-TDV group, the GMTs were 1.66 to 4.95-fold higher and 9.23 to 24.6-fold higher after the third injection compared with baseline in those who were dengue seropositive and dengue seronegative, respectively. Pain was the most commonly reported solicited injection site reaction after the first injection in both the CYD-TDV (6.3%) and placebo groups (4.9%), but occurred less frequently after subsequent injections. No serious adverse events were vaccine-related, no immediate unsolicited adverse events, and no virologically-confirmed cases of dengue, were reported during the study. The immunogenicity and safety of CYD-TDV was satisfactory in both dengue seropositive and seronegative Indian adults.

Keywords: CYD vaccine; India; dengue; immunogenicity; live attenuated vaccine; phase II trial; recombinant; safety; tetravalent dengue vaccine.

Figures

Figure 1.

Participant flow chart: summary of dispositions and discontinuations.

Figure 2.

Seropositivity rates (PRNT50 antibody titer ≥10 1/dil [95% CI]) against one, 2, 3 or 4 dengue virus serotypes at baseline and 28 days after each study injection given at 0, 6 and 12 months (FAS).

Figure 3.

Serotype-specific seropositivity rate (PRNT50 titer ≥10 1/dil [95% CI]) at baseline and 28 days after each study injection given at 0, 6 and 12 months (FAS).

Figure 4.

Geometric mean titres (GMTs [1/dil]) and 95% CIs for antibodies against each dengue virus serotype at baseline and 28 days after the 3 study injections given at 0, 6 and 12 months (FAS).

Figure 5.

Geometric mean titres (GMTs [1/dil]) and 95% CIs for antibodies against each dengue virus serotype at baseline and 28 days after the 3 study injections given at 0, 6 and 12 months in the CYD-TDV group by baseline dengue serostatus (FAS) (data for the placebo-injected group are not shown).