Joseph Torresi1,2, Peter C Richmond3,4, Leon G Heron5, Ming Qiao6,7, Joanne Marjason8, Linda Starr-Spires9, Diane van der Vliet10, Jing Jin11, T Anh Wartel12, Alain Bouckenooghe12. 1. Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne. 2. Department of Infectious Diseases, Austin Hospital, Heidelberg. 3. University of Western Australia School of Paediatrics and Child Health. 4. Vaccine Trials Group, Telethon Kids Institute, Subiaco. 5. National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases, Children's Hospital at Westmead, Westmead. 6. Royal Adelaide Hospital. 7. SA Pathology, Adelaide. 8. Q-Pharm, Herston, Australia. 9. Global Clinical Immunology, Sanofi Pasteur, Swiftwater, Pennsylvania. 10. Clinical Development, Sanofi Pasteur, Marcy l'Etoile, France. 11. Clinical Sciences and Operations, Sanofi, Beijing, China. 12. Clinical Sciences, Sanofi Pasteur, Singapore.
Abstract
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.
RCT Entities:
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.
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