Robust and Balanced Immune Responses to All 4 Dengue Virus Serotypes Following Administration of a Single Dose of a Live Attenuated Tetravalent Dengue Vaccine to Healthy, Flavivirus-Naive Adults

J Infect Dis. 2015 Sep 1;212(5):702-10. doi: 10.1093/infdis/jiv082. Epub 2015 Mar 22.


Background: The 4 serotypes of dengue virus, DENV-1-4, are the leading cause of arboviral disease globally. The ideal dengue vaccine would provide protection against all serotypes after a single dose.

Methods: Two randomized, placebo-controlled trials were performed with 168 flavivirus-naive adults to demonstrate the safety and immunogenicity of a live attenuated tetravalent dengue vaccine (TV003), compared with those of a second tetravalent vaccine with an enhanced DENV-2 component (TV005), and to evaluate the benefit of a booster dose at 6 months. Safety data, viremia, and neutralizing antibody titers were evaluated.

Results: A single dose of TV005 elicited a tetravalent response in 90% of vaccinees by 3 months after vaccination and a trivalent response in 98%. Compared with TV003, the higher-dose DENV-2 component increased the observed frequency of immunogenicity to DENV-2 in the TV005 trial. Both the first and second doses were well tolerated. Neither vaccine viremia, rash, nor a significant antibody boost were observed following a second dose.

Conclusions: A single subcutaneous dose of TV005 dengue vaccine is safe and induces a tetravalent antibody response at an unprecedented frequency among vaccinees. A second dose has limited benefit and appears to be unnecessary. Studies to confirm these findings and assess vaccine efficacy will now move to populations in regions where DENV transmission is endemic.

Clinical trials registration: NCT01072786 and NCT01436422.

Keywords: clinical trial; dengue vaccine; live attenuated tetravalent vaccine.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Dengue Vaccines / administration & dosage
  • Dengue Vaccines / adverse effects
  • Dengue Vaccines / immunology*
  • Dengue Virus / immunology*
  • Drug-Related Side Effects and Adverse Reactions
  • Female
  • Healthy Volunteers
  • Humans
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Placebos / administration & dosage
  • Vaccination / methods*
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / adverse effects
  • Vaccines, Attenuated / immunology
  • Viremia
  • Young Adult


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Dengue Vaccines
  • Placebos
  • Vaccines, Attenuated

Associated data