Live Attenuated Chimeric Yellow Fever Dengue Type 2 (Chimeri Vax -DEN2) Vaccine: Phase 1 clinical trial for safety and immunogenicity

Guirakhoo, Farshad, Kitchener, Scott, Morrison, Dennis, Forrat, Remi, McCarthy, Karen, Nichols, Richard, Yoksan, Sutee, Duan, Xiaochu, Ermak, Thomas H., Kanesa-thasan, Niranjan, Bedford, Philip, Lang, Jean, Quentin-Millet, Marie-Jose and Monath, Thomas P. (2006) Live Attenuated Chimeric Yellow Fever Dengue Type 2 (Chimeri Vax -DEN2) Vaccine: Phase 1 clinical trial for safety and immunogenicity. Human Vaccines, 2 2: 60-67.

Author Guirakhoo, Farshad
Kitchener, Scott
Morrison, Dennis
Forrat, Remi
McCarthy, Karen
Nichols, Richard
Yoksan, Sutee
Duan, Xiaochu
Ermak, Thomas H.
Kanesa-thasan, Niranjan
Bedford, Philip
Lang, Jean
Quentin-Millet, Marie-Jose
Monath, Thomas P.
Title Live Attenuated Chimeric Yellow Fever Dengue Type 2 (Chimeri Vax -DEN2) Vaccine: Phase 1 clinical trial for safety and immunogenicity
Journal name Human Vaccines   Check publisher's open access policy
ISSN 1554-8600
Publication date 2006
Sub-type Article (original research)
Volume 2
Issue 2
Start page 60
End page 67
Total pages 8
Editor Ronald W. Ellis
Place of publication United States
Publisher Landes Bioscience
Collection year 2006
Language eng
Subject CX
321010 Infectious Diseases
730299 Public health not elsewhere classified
Abstract 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-VAXâ by the subcutaneous route (SC). To determine the effect of YF pre-immunity on the ChimeriVaxTM-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 log10 PFU of ChimeriVaxTM-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) pre-immunity to YF virus does not interfere with ChimeriVaxTM-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.
Q-Index Code CX

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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Created: Wed, 15 Aug 2007, 10:24:11 EST