A single dose of Dengvaxia is associated with transient reduction in dengue infection risk among dengue-naïve children

Abstract

Dengvaxia ® induces antibody responses in dengue virus (DENV)-naïve children, but the durability of these responses and their impact on subsequent wild-type (WT) DENV infection remain unclear. Although previous studies have primarily evaluated vaccine efficacy against dengue disease, the impact of Dengvaxia ® on susceptibility to WT DENV infection and subsequent immune responses remains less well defined. We evaluated vaccine-induced immunity and susceptibility to WT DENV infection in a longitudinal cohort of 186 seronegative children, including 114 who received a single dose of Dengvaxia ® and 72 who remained unvaccinated, followed for 40 months. Samples collected at baseline and two follow-up time points (20 months [T1] and 40 months [T2]) were analyzed using yellow fever virus (YFV) non-structural protein 1 (NS1) antibody assays, which is expressed by Dengvaxia ® but not by WT DENV, enabling discrimination between vaccine-associated and WT infection-induced responses. At T1, 61% of vaccinated children were responders. Additional low-level YFV NS1 antibody responses were detected in some children originally classified as vaccine non-responders, suggesting that the predefined binary classification may not capture the full range of vaccine-associated antibody responses. Low-level YFV NS1 responses remained detectable through T2. During the first follow-up period (baseline-T1), vaccination was associated with a reduced risk of WT DENV infection (vaccine effectiveness [VE]=45%). During the second period (T1-T2), no difference in infection risk was detected between groups. Following breakthrough infection during the first follow-up period, vaccinated children developed antibody responses with greater magnitude and broader serotype breadth than unvaccinated children with primary infection, consistent with vaccine-associated immune priming following WT DENV infection. In contrast, during the second period (T1-T2), differences in antibody magnitude and breadth following infection were no longer detected between groups. Together, these findings suggest that a single dose of Dengvaxia ® in DENV-seronegative children was associated with a reduced risk of WT DENV infection and with differences in subsequent antibody responses during the first follow-up period, but these associations were no longer observed during the second period.