Biodistribution and safety of a live attenuated tetravalent dengue vaccine in the cynomolgus monkey. Issue 43 (13th October 2017)

• Record Type: Journal Article
• Authors: Ravel, Guillaume; Mantel, Nathalie; Silvano, Jeremy; Rogue, Alexandra; Guy, Bruno; Jackson, Nicholas; Burdin, Nicolas
• Is Part Of: Vaccine. Volume 35:Issue 43(2017)
• Page Start: 5918
• Page End: 5923
• Publication Date: 2017-10-13
• Subjects: Live attenuated vaccine -- Dengue -- Cynomolgus monkey -- Toxicity -- Biodistribution -- Shedding; CYD-TDV live attenuated tetravalent dengue vaccine -- DENV dengue virus -- DF dengue fever -- DHF dengue hemorrhagic fever -- DSS dengue shock syndrome -- ELISA enzyme-linked immunosorbent assay -- LLOQ lower limit of quantification -- NHPs non-human primates -- PBS phosphate buffered saline -- PRNT50 plaque reduction neutralization test 50 -- qRT-PCR quantitative reverse transcriptase polymerase chain reaction -- sc subcutaneous -- WHO World Health Organization -- wt wild-type -- YF yellow fever -- YF-NS5 yellow fever NS5 gene; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2017.08.071
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Subcutaneous live, attenuated, tetravalent dengue virus vaccine (CYD-TDV) was well tolerated. No toxicological findings other than minor local reactions at the injection site. Transient low level of CYD-TDV RNA detected primarily in blood, the injection site and draining lymph nodes. Absence of toxicological concern with CYD-TDV. Abstract: 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 (5 log10 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.