title: Interference and facilitation between dengue serotypes in a tetravalent live dengue virus vaccine candidate.
abstract: BACKGROUND
  Live, multivalent vaccines have historically exhibited interference in humans; live dengue virus (DENV) vaccines have proven no exception.
  
  
  METHODS
  To characterize interactions between DENV serotypes in a tetravalent live-attenuated virus vaccine candidate, we analyzed data from a factorial clinical trial in which all combinations of high- and low-dose DENV serotypes were combined in 16 live-attenuated tetravalent vaccine formulations (N = 64) and administered to flavivirus-naive adult volunteers. Regression models considered the outcomes of reactogenicity and seroconversion, controlling for all serotype doses simultaneously. Additionally, results were compared against earlier evaluations of the same viruses administered as monovalent formulations.
  
  
  RESULTS
  DENV-1 was immunologically dominant in both monovalent and tetravalent formulations. In tetravalent formulations, DENV-1 and DENV-2 antagonized each other, with a high dose of one decreasing seroconversion to the other. However, high-dose DENV-1 significantly increased seroconversion against 3 or more serotypes, increasing seroconversion to DENV-1, DENV-3, and DENV-4. The highest reactogenicity occurred when DENV-1 was at high dose and all others were low; reactogenicity decreased with the incorporation of other high-dose serotypes.
  
  
  CONCLUSIONS
  Interference and facilitation occurred between serotypes in the live vaccine candidate evaluated. These analyses suggest that it may be possible to exploit facilitation to increase overall seroconversion.
authors: Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia 30322, USA. kbander@learnlink.emory.edu
authors: Kathryn B
authors: KB
authors: Anderson
authors: Robert V
authors: RV
authors: Gibbons
authors: Robert
authors: R
authors: Edelman
authors: Kenneth H
authors: KH
authors: Eckels
authors: Robert J
authors: RJ
authors: Putnak
authors: Bruce L
authors: BL
authors: Innis
authors: Wellington
authors: W
authors: Sun
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D002986:Clinical Trials as Topic; D053059:Dengue Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D003716:Dengue Virus / Q000145:classification*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D016015:Logistic Models; D012703:Serotyping; D014611:Vaccination / Q000009:adverse effects
chemical_list: D000914:Antibodies, Viral; D053059:Dengue Vaccines