title: rDEN4delta30, a live attenuated dengue virus type 4 vaccine candidate, is safe, immunogenic, and highly infectious in healthy adult volunteers.
abstract: BACKGROUND
  The live attenuated dengue virus type 4 (DEN-4) vaccine candidate virus rDEN4 Delta 30 was previously found to be safe and immunogenic at a dose of 10(5) plaque-forming units (pfu).
  
  
  METHODS
  In a follow-up placebo-controlled phase 2 clinical trial, rDEN4 Delta 30 was administered as a single inoculation to 3 separate dose cohorts (10(3) pfu, 10(2) pfu, or 10(1) pfu), for further evaluation. Each dose cohort consisted of 20 vaccinees and 4 placebo recipients. Volunteers were monitored closely for adverse events, and serum was collected on study days 28 and 42 for determination of neutralizing antibody titer.
  
  
  RESULTS
  The vaccine was well tolerated at all doses studied. The most common adverse events observed were a transient asymptomatic rash in >50% of vaccinees and a mild neutropenia in approximately 20% of vaccinees. No vaccinee developed a dengue-like illness. The vaccine was highly infectious and immunogenic, with 95%-100% of vaccinees in each dose cohort developing a >/=4-fold increase in titers of serum neutralizing antibodies against DEN-4.
  
  
  CONCLUSIONS
  The rDEN4 Delta 30 vaccine is safe and induced an antibody response that was broadly neutralizing against genotypically diverse DEN-4 viruses. It is a promising vaccine candidate for inclusion in a tetravalent dengue vaccine formulation.
authors.affiliation: Center for Immunization Research, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA. adurbin@jhsph.edu
authors.forename: Anna P
authors.initials: AP
authors.lastname: Durbin
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Whitehead
authors.forename: Julie
authors.initials: J
authors.lastname: McArthur
authors.forename: John R
authors.initials: JR
authors.lastname: Perreault
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Blaney
authors.forename: Bhavin
authors.initials: B
authors.lastname: Thumar
authors.forename: Brian R
authors.initials: BR
authors.lastname: Murphy
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Karron
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology*; D004311:Double-Blind Method; D003875:Drug Eruptions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014766:Viremia
chemical_list: D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014765:Viral Vaccines