On guard: on India and the Qdenga dengue vaccine

The CDSCO’s approval of the Qdenga dengue vaccine — the first in India’s history — follows the vaccine’s licensing in over 40 countries and a WHO prequalification, and some of the country’s worst dengue years vis-à-vis the disease’s burden, although that is evidence of better surveillance as well. The Aedes mosquitoes that spread the disease are expanding into semi-urban and rural districts, where conventional vector control is harder to sustain. The time to develop the vaccine itself is understandable. The four antigenically distinct dengue serotypes and the possibility of a ‘second infection’ by a different serotype producing more severe disease through antibody-dependent enhancement mean that an effective shot has to induce strong immunity against all four at once. This constraint nearly derailed the first licensed dengue vaccine, Dengvaxia, and the controversy in the Philippines in 2017 prompted greater regulatory caution. The design of Qdenga, by Japan-based Takeda, differs from that of Dengvaxia and, unlike the latter, can be administered without screening for a prior dengue infection.

Its protection against the serotypes varies from highest against DENV-2, followed by DENV-1, while uncertainty remains regarding protection against DENV-3 and DENV-4 in people without prior exposure to dengue. This is concerning because while DENV-2 is more common in India, DENV-3 prevalence is increasing. If the DENV-3 serotype dominates the 2026 monsoon season, Qdenga’s impact could be substantially lower than anticipated, especially if many recipients are dengue-naïve. Qdenga also requires two doses across three months apart. Clinical data suggest that the first dose protects unevenly, with stronger evidence against DENV-1 and DENV-2 than DENV-3 and DENV-4. If a seronegative person takes the first shot on July 1, when the monsoon begins, and encounters DENV-3 in August, the shot may not suffice to prevent severe illness. Ensuring the highly mobile migrant workforce receives its second dose will be significantly difficult, too; those falling through the cracks may also be exposed to concerns raised in the TIDES trial of a ‘negative efficacy’ against hospitalisation related to DENV-3 among seronegative children. Finally, following Takeda’s tiered pricing strategy worldwide, Qdenga may be too expensive for people living in dense urban slums with poor drainage. To ensure sufficient uptake among the populations at greatest risk, the government must negotiate a lower price. In the end, administering a dengue vaccine properly in a population is no less tricky than developing a vaccine against dengue, and the Qdenga rollout should give no cause for complacency.