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

Henrik Salje (1, 2) , Maria Theresa Alera (3) , Mary Noreen Chua (4) , Taweewun Hunsawong (3) , Damon Ellison (5) , Anon Srikiatkhachorn (3, 6, 7) , Richard G. Jarman (5) , Gregory D. Gromowski (5) , Isabel Rodriguez-Barraquer (8) , Simon Cauchemez (9) , Derek A. T. Cummings (2) , Louis Macareo (3) , In-Kyu Yoon (10) , Stefan Fernandez (3) , Alan L. Rothman (6)

1 CAM - University of Cambridge [UK]
2 UF - University of Florida [Gainesville]
3 AFRIMS - Armed Forces Research Institute of Medical Sciences [Bangkok]
4 Chong Hua Hospital [Cebu City, Philippines]
5 Walter Reed Army Institute of Research
6 URI - University of Rhode Island
7 KMUTNB - King Mongkut's University of Technology North Bangkok
8 UC San Francisco - University of California [San Francisco]
9 Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases
10 CEPI - Coalition for Epidemic Preparedness Innovations [Washington, DC, États-Unis]

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.

Domaines: Statistiques [math.ST]

Henrik Salje, Maria Theresa Alera, Mary Noreen Chua, Taweewun Hunsawong, Damon Ellison, et al.. Evaluation of extended efficacy of Dengvaxia vaccine against symptomatic and subclinical dengue infection. Nature Medicine, 2021, 27 (8), pp.1395-1400. ⟨10.1038/s41591-021-01392-9⟩. ⟨pasteur-03330600⟩