Replication and Excretion of the Live Attenuated Tetravalent Dengue Vaccine CYD-TDV in a Flavivirus-Naive Adult Population: Assessment of Vaccine Viremia and Virus Shedding.

Autor:	Torresi J; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne.; Department of Infectious Diseases, Austin Hospital, Heidelberg., Richmond PC; University of Western Australia School of Paediatrics and Child Health.; Vaccine Trials Group, Telethon Kids Institute, Subiaco., Heron LG; National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases, Children's Hospital at Westmead, Westmead., Qiao M; Royal Adelaide Hospital.; SA Pathology, Adelaide., Marjason J; Q-Pharm, Herston, Australia., Starr-Spires L; Global Clinical Immunology, Sanofi Pasteur, Swiftwater, Pennsylvania., van der Vliet D; Clinical Development, Sanofi Pasteur, Marcy l'Etoile, France., Jin J; Clinical Sciences and Operations, Sanofi, Beijing, China., Wartel TA; Clinical Sciences, Sanofi Pasteur, Singapore., Bouckenooghe A; Clinical Sciences, Sanofi Pasteur, Singapore.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2017 Oct 17; Vol. 216 (7), pp. 834-841.
DOI:	10.1093/infdis/jix314
Abstrakt:	Background: We assessed replication and excretion of the live attenuated tetravalent dengue vaccine (CYD-TDV) into biological fluids following vaccination in dengue-naive adults in Australia. Methods: Vaccinal viremia/shedding was assessed in a subset of participants enrolled in a lot-to-lot consistency study; 95 participants received 3 subcutaneous doses of CYD-TDV from phase 2/3 lots of the vaccine, and 8 received placebo; doses were administered 6 months apart. Quantitative reverse-transcription polymerase chain reaction (qR-PCR) analysis was used to initially detect the yellow fever virus (YFV) core protein gene in the backbone of CYD-TDV in serum, saliva and urine, followed by serotype-specific qRT-PCR analysis of samples positive for YFV by qRT-PCR (lower limit of detection, 5.16 GEq/mL). Results: YFV viremia was detected by qRT-PCR in 69.5% of participants (66 of 95) who received CYD-TDV, mainly 6-14 days after injection 1. The serotypes detected were serotype 4 (in 68.2% of participants [45 of 95]), serotype 3 (in 19.7% [13 of 95]), and serotype 1 (in 12.1% [8 of 95]); serotype 2 was not detected. None of the placebo recipients had vaccinal viremia/shedding. No participants had detectable viral shedding into saliva at levels above the lower limit of quantitation. Two participants had low-level viral shedding (serotype 3) in urine (5.47 and 5.77 GEq/mL). None of the participants with viremia or shedding experienced concomitant fever. Conclusions: Low-level vaccinal viremia may occur following vaccination with CYD-TDV, but this is not associated with any symptom or adverse event. Clinical Trials Registration: NCT01134263. (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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