title: Estimation of parameters related to vaccine efficacy and dengue transmission from two large phase III studies.
abstract: A tetravalent dengue vaccine was shown to be efficacious against symptomatic dengue in two phase III efficacy studies performed in five Asian and five Latin American countries. The objective here was to estimate key parameters of a dengue transmission model using the data collected during these studies.
  
  
  
  Parameter estimation was based on a Sequential Monte Carlo approach and used a cohort version of the transmission model. Serotype-specific basic reproduction numbers were derived for each country. Parameters related to serotype interactions included duration of cross-protection and level of cross-enhancement characterized by differences in symptomaticity for primary, secondary and post-secondary infections. We tested several vaccine efficacy profiles and simulated the evolution of vaccine efficacy over time for the scenarios providing the best fit to the data.
  
  
  
  Two reference scenarios were identified. The first included temporary cross-protection and the second combined cross-protection and cross-enhancement upon wild-type infection and following vaccination. Both scenarios were associated with differences in efficacy by serotype, higher efficacy for pre-exposed subjects and against severe dengue, increase in efficacy with doses for naïve subjects and by a more important waning of vaccine protection for subjects when naïve than when pre-exposed. Over 20 years, the median reduction of dengue risk induced by the direct protection conferred by the vaccine ranged from 24% to 47% according to country for the first scenario and from 34% to 54% for the second.
  
  
  
  Our study is an important first step in deriving a general framework that combines disease dynamics and mechanisms of vaccine protection that could be used to assess the impact of vaccination at a population level.
authors.affiliation: Vaccination Value Modeling, Sanofi Pasteur, Lyon, France. Electronic address: laurent.coudeville@sanofipasteur.com.
authors.forename: Laurent
authors.initials: L
authors.lastname: Coudeville
authors.affiliation: Vaccination Value Modeling, Sanofi Pasteur, Lyon, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Baurin
authors.affiliation: MaIAGE, INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Elisabeta
authors.initials: E
authors.lastname: Vergu
mesh_terms: D001208:Asia; D050936:Basic Reproduction Number; D017326:Clinical Trials, Phase III as Topic; D003715:Dengue / Q000517:prevention & control* / Q000635:transmission*; D053059:Dengue Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D006801:Humans; D007843:Latin America; D015233:Models, Statistical; D016896:Treatment Outcome
chemical_list: D053059:Dengue Vaccines
keywords: Dengue; Flavivirus; Modeling; Tetravalent dengue vaccine