Live attenuated chimeric yellow fever dengue type 2 (ChimeriVax™- DEN2) vaccine: Phase I clinical trial for safety and immunogenicity - Effect of yellow fever pre-immunity in induction of cross neutralizing antibody responses to all 4 dengue serotypes
A randomized double-blind Phase I Trial was conducted to evaluate safety, tolerability, and immunogenicity of a yellow fever (YF)-dengue 2 (DEN2) chimera (ChimeriVax™-DEN2) in comparison to that of YF vaccine (YF-VAX®). Forty-two healthy YF naïve adults randomly received a single dose of either Chim...
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th-mahidol.233772018-08-20T14:25:34Z Live attenuated chimeric yellow fever dengue type 2 (ChimeriVax™- DEN2) vaccine: Phase I clinical trial for safety and immunogenicity - Effect of yellow fever pre-immunity in induction of cross neutralizing antibody responses to all 4 dengue serotypes Farshad Guirakhoo Scott Kitckener Dennis Morrison Remi Forrat Karen McCarthy Richard Nichols Sutee Yoksan Xiaochu Duan Thomas H. Ermak Niranjan Kanesa-Thasan Philip Bedford Jean Lang Marie Jose Quentin-Millet Thomas P. Monath Acambis Bio-Kinetic Clinical Applications Sanofi Pasteur Mahidol University University of Queensland Immunology and Microbiology Pharmacology, Toxicology and Pharmaceutics A randomized double-blind Phase I Trial was conducted to evaluate safety, tolerability, and immunogenicity of a yellow fever (YF)-dengue 2 (DEN2) chimera (ChimeriVax™-DEN2) in comparison to that of YF vaccine (YF-VAX®). Forty-two healthy YF naïve adults randomly received a single dose of either ChimeriVax™-DEN2 (high dose, 5 log plaque forming units [PFU] or low dose, 3 log PFU) or YF-VAX® by the subcutaneous route (SC). To determine the effect of YF preimmunity on the ChimeriVax™-DEN2 vaccine, 14 subjects previously vaccinated against YF received a high dose of ChimeriVax™-DEN2 as an open-label vaccine. Most adverse events were similar to YF-VAX® and of mild to moderate intensity, with no serious side-effects. One hundred percent and 92.3% of YF naïve subjects inoculated with 5.0 and 3.0 log10PFU of ChimeriVax™-DEN2, respectively, seroconverted to wt DEN2 (strain 16681); 92% of subjects inoculated with YF-VAX® seroconverted to YF 17D virus but none of YF naïve subjects inoculated with ChimeriVax-DEN2 seroconverted to YF 17D virus. Low seroconversion rates to heterologous DEN serotypes 1, 3 and 4 were observed in YF naïve subjects inoculated with either ChimeriVax™-DEN2 or YF-VAX®. In contrast, 100% of YF immune subjects inoculated with ChimeriVax™-DEN2 seroconverted to all 4 DEN serotypes. Surprisingly, levels of neutralizing antibodies to DEN 1, 2 and 3 viruses in YF immune subjects persisted after 1 year. These data demonstrated that (1) the safety and immunogenicity profile of the ChimeriVax™-DEN2 vaccine is consistent with that of YF-VAX®, and (2) preimmunity to YF virus does not interfere with ChimeriVax™-DEN2 immunization, but induces a long lasting and cross neutralizing antibody response to all 4 DEN serotypes. The latter observation can have practical implications toward development of a dengue vaccine. ©2006 Landes Bioscience. 2018-08-20T07:03:32Z 2018-08-20T07:03:32Z 2006-01-01 Article Human Vaccines. Vol.2, No.2 (2006), 60-67 10.4161/hv.2.2.2555 15548619 15548600 2-s2.0-33745237160 https://repository.li.mahidol.ac.th/handle/123456789/23377 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=33745237160&origin=inward |
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Immunology and Microbiology Pharmacology, Toxicology and Pharmaceutics Farshad Guirakhoo Scott Kitckener Dennis Morrison Remi Forrat Karen McCarthy Richard Nichols Sutee Yoksan Xiaochu Duan Thomas H. Ermak Niranjan Kanesa-Thasan Philip Bedford Jean Lang Marie Jose Quentin-Millet Thomas P. Monath Live attenuated chimeric yellow fever dengue type 2 (ChimeriVax™- DEN2) vaccine: Phase I clinical trial for safety and immunogenicity - Effect of yellow fever pre-immunity in induction of cross neutralizing antibody responses to all 4 dengue serotypes |
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A randomized double-blind Phase I Trial was conducted to evaluate safety, tolerability, and immunogenicity of a yellow fever (YF)-dengue 2 (DEN2) chimera (ChimeriVax™-DEN2) in comparison to that of YF vaccine (YF-VAX®). Forty-two healthy YF naïve adults randomly received a single dose of either ChimeriVax™-DEN2 (high dose, 5 log plaque forming units [PFU] or low dose, 3 log PFU) or YF-VAX® by the subcutaneous route (SC). To determine the effect of YF preimmunity on the ChimeriVax™-DEN2 vaccine, 14 subjects previously vaccinated against YF received a high dose of ChimeriVax™-DEN2 as an open-label vaccine. Most adverse events were similar to YF-VAX® and of mild to moderate intensity, with no serious side-effects. One hundred percent and 92.3% of YF naïve subjects inoculated with 5.0 and 3.0 log10PFU of ChimeriVax™-DEN2, respectively, seroconverted to wt DEN2 (strain 16681); 92% of subjects inoculated with YF-VAX® seroconverted to YF 17D virus but none of YF naïve subjects inoculated with ChimeriVax-DEN2 seroconverted to YF 17D virus. Low seroconversion rates to heterologous DEN serotypes 1, 3 and 4 were observed in YF naïve subjects inoculated with either ChimeriVax™-DEN2 or YF-VAX®. In contrast, 100% of YF immune subjects inoculated with ChimeriVax™-DEN2 seroconverted to all 4 DEN serotypes. Surprisingly, levels of neutralizing antibodies to DEN 1, 2 and 3 viruses in YF immune subjects persisted after 1 year. These data demonstrated that (1) the safety and immunogenicity profile of the ChimeriVax™-DEN2 vaccine is consistent with that of YF-VAX®, and (2) preimmunity to YF virus does not interfere with ChimeriVax™-DEN2 immunization, but induces a long lasting and cross neutralizing antibody response to all 4 DEN serotypes. The latter observation can have practical implications toward development of a dengue vaccine. ©2006 Landes Bioscience. |
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Acambis |
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Acambis Farshad Guirakhoo Scott Kitckener Dennis Morrison Remi Forrat Karen McCarthy Richard Nichols Sutee Yoksan Xiaochu Duan Thomas H. Ermak Niranjan Kanesa-Thasan Philip Bedford Jean Lang Marie Jose Quentin-Millet Thomas P. Monath |
format |
Article |
author |
Farshad Guirakhoo Scott Kitckener Dennis Morrison Remi Forrat Karen McCarthy Richard Nichols Sutee Yoksan Xiaochu Duan Thomas H. Ermak Niranjan Kanesa-Thasan Philip Bedford Jean Lang Marie Jose Quentin-Millet Thomas P. Monath |
author_sort |
Farshad Guirakhoo |
title |
Live attenuated chimeric yellow fever dengue type 2 (ChimeriVax™- DEN2) vaccine: Phase I clinical trial for safety and immunogenicity - Effect of yellow fever pre-immunity in induction of cross neutralizing antibody responses to all 4 dengue serotypes |
title_short |
Live attenuated chimeric yellow fever dengue type 2 (ChimeriVax™- DEN2) vaccine: Phase I clinical trial for safety and immunogenicity - Effect of yellow fever pre-immunity in induction of cross neutralizing antibody responses to all 4 dengue serotypes |
title_full |
Live attenuated chimeric yellow fever dengue type 2 (ChimeriVax™- DEN2) vaccine: Phase I clinical trial for safety and immunogenicity - Effect of yellow fever pre-immunity in induction of cross neutralizing antibody responses to all 4 dengue serotypes |
title_fullStr |
Live attenuated chimeric yellow fever dengue type 2 (ChimeriVax™- DEN2) vaccine: Phase I clinical trial for safety and immunogenicity - Effect of yellow fever pre-immunity in induction of cross neutralizing antibody responses to all 4 dengue serotypes |
title_full_unstemmed |
Live attenuated chimeric yellow fever dengue type 2 (ChimeriVax™- DEN2) vaccine: Phase I clinical trial for safety and immunogenicity - Effect of yellow fever pre-immunity in induction of cross neutralizing antibody responses to all 4 dengue serotypes |
title_sort |
live attenuated chimeric yellow fever dengue type 2 (chimerivax™- den2) vaccine: phase i clinical trial for safety and immunogenicity - effect of yellow fever pre-immunity in induction of cross neutralizing antibody responses to all 4 dengue serotypes |
publishDate |
2018 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/23377 |
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1763491137747681280 |