title: Heterotypic dengue infection with live attenuated monotypic dengue virus vaccines: implications for vaccination of populations in areas where dengue is endemic.
abstract: BACKGROUND
  Because infection with any of the 4 Dengue virus serotypes may elicit both protective neutralizing antibodies and nonneutralizing antibodies capable of enhancing subsequent heterotypic Dengue virus infections, the greatest risk for severe dengue occurs during a second, heterotypic Dengue virus infection. It remains unclear whether the replication of live attenuated vaccine viruses will be similarly enhanced when administered to Dengue-immune individuals.
  
  
  METHODS
  We recruited 36 healthy adults who had previously received a monovalent live Dengue virus vaccine 0.6-7.4 years earlier. Participants were assigned to 1 of 4 cohorts and were randomly chosen to receive placebo or a heterotypic vaccine. The level of replication, safety, and immunogenicity of the heterotypic vaccine virus was compared with that of Dengue virus immunologically naive vaccinees.
  
  
  RESULTS
  Vaccine virus replication and reactogenicity after monovalent Dengue virus vaccination in naive and heterotypically immune vaccinees was similar. In contrast to naive vaccinees, the antibody response in heterotypically immune vaccinees was broadly neutralizing and mimicked the response observed by natural secondary Dengue virus infection.
  
  
  CONCLUSIONS
  Enhanced replication of these live attenuated Dengue virus vaccines was minimal in heterotypically immune vaccinees and suggests that the further evaluation of these candidate vaccines in populations with preexisting DENV immunity can proceed safely.
authors.affiliation: Center for Immunization Research, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. adurbin@jhsph.edu
authors.forename: Anna P
authors.initials: AP
authors.lastname: Durbin
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmidt
authors.forename: Dan
authors.initials: D
authors.lastname: Elwood
authors.forename: Kimberli A
authors.initials: KA
authors.lastname: Wanionek
authors.forename: Janece
authors.initials: J
authors.lastname: Lovchik
authors.forename: Bhavin
authors.initials: B
authors.lastname: Thumar
authors.forename: Brian R
authors.initials: BR
authors.lastname: Murphy
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Whitehead
mesh_terms: D000328:Adult; D003715:Dengue / Q000453:epidemiology / Q000473:pathology* / Q000517:prevention & control*; D053059:Dengue Vaccines / Q000145:classification / Q000276:immunology*; D003716:Dengue Virus / Q000145:classification / Q000502:physiology*; D019353:Endemic Diseases; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D014766:Viremia; D055815:Young Adult
chemical_list: D053059:Dengue Vaccines