Development and clinical evaluation of multiple investigational monovalent DENV vaccines to identify components for inclusion in a live attenuated tetravalent DENV vaccine

被引:98
作者
Durbin, Anna P. [1 ]
Kirkpatrick, Beth D. [2 ,3 ,4 ]
Pierce, Kristen K. [2 ,3 ,4 ]
Schmidt, Alexander C. [5 ]
Whitehead, Stephen S. [5 ]
机构
[1] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Ctr Immunizat Res, Baltimore, MD 21205 USA
[2] Univ Vermont, Coll Med, Vaccine Testing Ctr, Burlington, VT USA
[3] Univ Vermont, Coll Med, Infect Dis Unit, Burlington, VT USA
[4] Univ Vermont, Coll Med, Div Infect Dis, Burlington, VT USA
[5] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA
关键词
Dengue; Vaccine development; Clinical trial; DENGUE-VIRUS TYPE-4; ANTIBODY-DEPENDENT ENHANCEMENT; HEALTHY ADULT VOLUNTEERS; FLAVIVIRUS-NAIVE ADULTS; 3' UNTRANSLATED REGION; RHESUS-MONKEYS; 3'-UNTRANSLATED REGION; HEMORRHAGIC-FEVER; VERO CELLS; CANDIDATE;
D O I
10.1016/j.vaccine.2011.07.023
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The Laboratory of Infectious Diseases at the National Institute of Allergy and Infectious Diseases, National Institutes of Health has been engaged in an effort to develop a safe, efficacious, and affordable live attenuated tetravalent dengue vaccine (LATV) for more than ten years. Numerous recombinant monovalent DENV vaccine candidates have been evaluated in the SCID-HuH-7 mouse and in rhesus macaques to identify those candidates with a suitable attenuation phenotype. In addition, the ability of these candidates to infect and disseminate in Aedes mosquitoes had also been determined. Those candidates that were suitably attenuated in SCID-HuH-7 mice, rhesus macaques, and mosquitoes were selected for further evaluation in humans. This review will describe the generation of multiple candidate vaccines directed against each DENV serotype, the preclinical and clinical evaluation of these candidates, and the process of selecting suitable candidates for inclusion in a LAW dengue vaccine. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:7242 / 7250
页数:9
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