Biodistribution and safety of a live attenuated tetravalent dengue vaccine in the cynomolgus monkey

Vaccine. 2017 Oct 13;35(43):5918-5923. doi: 10.1016/j.vaccine.2017.08.071. Epub 2017 Sep 4.


Background: The first licensed dengue vaccine is a recombinant, live, attenuated, tetravalent dengue virus vaccine (CYD-TDV; Sanofi Pasteur). This study assessed the biodistribution, shedding, and toxicity of CYD-TDV in a non-human primate model as part of the nonclinical safety assessment program for the vaccine.

Methods: Cynomolgus monkeys were given one subcutaneous injection of either one human dose (5log10 CCID50/serotype) of CYD-TDV or saline control. Study endpoints included clinical observations, body temperature, body weight, food consumption, clinical pathology, immunogenicity, and post-mortem examinations including histopathology. Viral load, distribution, persistence, and shedding in tissues and body fluids were evaluated by quantitative reverse transcriptase polymerase chain reaction.

Results: The subcutaneous administration of CYD-TDV was well tolerated. There were no toxicological findings other than expected minor local reactions at the injection site. A transient low level of CYD-TDV viral RNA was detected in blood and the viral genome was identified primarily at the injection site and in the draining lymph nodes following immunization.

Conclusions: These results, together with other data from repeat-dose toxicity and neurovirulence studies, confirm the absence of toxicological concern with CYD-TDV and corroborate clinical study observations.

Keywords: Biodistribution; Cynomolgus monkey; Dengue; Live attenuated vaccine; Shedding; Toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / immunology
  • Dengue / immunology
  • Dengue / prevention & control*
  • Dengue Vaccines / adverse effects*
  • Dengue Vaccines / immunology*
  • Dengue Virus / immunology
  • Female
  • Genome, Viral / immunology
  • Macaca fascicularis / immunology*
  • Macaca fascicularis / virology
  • Male
  • Tissue Distribution / immunology*
  • Vaccination / adverse effects
  • Vaccines, Attenuated / adverse effects*
  • Vaccines, Attenuated / immunology*
  • Viral Load / immunology


  • Antibodies, Viral
  • Dengue Vaccines
  • Vaccines, Attenuated