Dengue Vaccine Effective Against All 4 Serotypes

Promising results from an ongoing study demonstrated the safety and immunogenicity of the tetravalent dengue vaccine (TDV) against all 4 dengue serotypes, which is currently being developed by Takeda. 

The phase 2 randomized, double-blind, placebo-controlled trial recruited 1800 children from 2 to 17 years of age living in the Dominican Republic, Panama, and the Philippines. Participants were divided into 4 groups and received either 2 TDV doses 3 months apart (group 1; n=201), 1 TDV dose (group 2; n=398), 1 TDV dose and a booster dose 1 year later (group 3; n=1002), or placebo (group 4; n=199). For the 18-month interim analysis, the researchers assessed dengue (DENV) serotype-specific antibody geometric mean titres (GMTs) in a per-protocol immunogenicity subset on days 1, 28, 91, 180, 365, and 540. In addition, they examined solicited and unsolicited safety and serious adverse events.
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Overall, 1794 participants received at least 1 dose of TDV or placebo. A total of 562 participants were included in the immunogenicity subset and 509 were included in the per-protocol set.

Eighteen months after vaccination, the antibody titres remained elevated in all TDV groups.

At day 540, the GMTs for DENV-1 were 476 for group 1, 461 for group 2, 1056 for group 3, and 92 for group 4. At day 540, the GMTs for DENV-2 were 1212 for group 1, 1242 for group 2, 1457 for group 3, and 177 for group 4. At day 540, DENV-3 GMTs were 286 for group 1, 298 for group 2, 548 for group 3, and 78 for group 4. At day 540, the DENV-4 GMT were 98 for group 1, 102 for group 2, 172 for group 3, and 33 for group 4.

The researchers observed limited differences in GMTs between groups 1 and 2, and a clear increase in GMTs following the 1-year booster among participants who were seronegative at baseline. 

In addition, vaccinate-related unsolicited adverse events occurred in 14 (2%) out of 562 participants, but there were no serious adverse events. Twenty-one participants (1.3%) out of 1596 who received the vaccine had symptomatic, virologically confirmed dengue compared with 9 (4.5%) out of 198 participants who received placebo.

“TDV was well tolerated and immunogenic against all four dengue serotypes, irrespective of baseline dengue serostatus,” the researchers concluded. “These data provide proof of concept for TDV and support the ongoing phase 3 efficacy assessment of two doses 3 months apart.”

—Melissa Weiss

Reference:

Sáez-Llorens X, Tricou V, Yu D, et al. Immunogenicity and safety of one versus two doses of tetravalent dengue vaccine in healthy children aged 2–17 years in Asia and Latin America: 18-month interim data from a phase 2, randomised, placebo-controlled study [published online November 6, 2017]. Lancet Infect Dis. http://dx.doi.org/10.1016/S1473-3099(17)30632-1.