Evaluation of the extended efficacy of the Dengvaxia vaccine against symptomatic and subclinical dengue infection

Multiyear analysis of antibody responses in recipients of the dengue vaccine Dengvaxia in the Philippines supports their utility as a predictor of protection against disease, and reveals that Dengvaxia efficacy declines 3 years after complete vaccination. More than half of the world's population lives in areas at risk for dengue virus infection. A vaccine will be pivotal to controlling spread, however, the only licensed vaccine, Dengvaxia, has been shown to increase the risk of severe disease in a subset of individuals. Vaccine efforts are hampered by a poor understanding of antibody responses, including those generated by vaccines, and whether antibody titers can be used as a marker of protection from infection or disease. Here we present the results of an ancillary study to a phase III vaccine study (n = 611). All participants received three doses of either Dengvaxia or placebo and were followed for 6 years. We performed neutralization tests on annual samples and during confirmed dengue episodes (n = 16,508 total measurements). We use mathematical models to reconstruct long-term antibody responses to vaccination and natural infection, and to identify subclinical infections. There were 87 symptomatic infections reported, and we estimated that there were a further 351 subclinical infections. Cumulative vaccine efficacy was positive for both subclinical and symptomatic infection, although the protective effect of the vaccine was concentrated in the first 3 years following vaccination. Among individuals with the same antibody titer, we found no difference between the risk of subsequent infection or disease between placebo and vaccine recipients, suggesting that antibody titers are a good predictor of both protection and disease risk.

Automated summary

A multiyear analysis of antibody responses in recipients of the Dengvaxia vaccine in the Philippines shows that antibody titers are a predictor of protection against disease, but the vaccine efficacy declines 3 years after complete vaccination. There is a need for better understanding of antibody responses to vaccines and their role in protecting against disease.