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

Publication date: 13 October 2017
Source:Vaccine, Volume 35, Issue 43
Author(s): Guillaume Ravel, Nathalie Mantel, Jeremy Silvano, Alexandra Rogue, Bruno Guy, Nicholas Jackson, Nicolas Burdin
BackgroundThe 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.MethodsCynomolgus 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.ResultsThe 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.ConclusionsThese 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.



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