Safety of a tetravalent live dengue virus vaccine in children responding to one serotype only.

Dengue virus (DENV) vaccines should be designed to induce balanced protective immunity to all 4 DENV serotypes to mitigate the risk of vaccine-enhanced dengue disease. The first tetravalent live DENV vaccine (Dengvaxia) tested in humans was efficacious in children who were partially immune to DENV at baseline. In DENV-naive children, the vaccine was not efficacious and placed some children at risk of more severe WT DENV breakthrough infections. To define dengue vaccine responses at the individual patient level and their relationship to mild and severe dengue infections, we prospectively studied a cohort of DENV-naive children who received 1 dose of Dengvaxia. The vaccine stimulated variable responses that neutralized 0, 1 (monotypic), or 2+ (multitypic) serotypes in individual children. Using a logistic regression model, we found that vaccinated children with neutralizing antibody (NAb) to 1 serotype only were at greater risk developing dengue compared with children who were not vaccinated (odds ratio 5.07). This risk was not observed in vaccinated children with no NAb or NAb to 2 or more serotypes. We propose that individuals with durable NAb to 1 serotype have an abundance of serotype cross-reactive, nonneutralizing antibodies implicated in the enhanced replication of heterologous serotypes.