Evaluation of a prototype dengue-1 DNA vaccine in a Phase 1 clinical trial

被引:106
作者
Beckett, Charmagne G. [1 ]
Tjaden, Jeffrey [1 ]
Burgess, Timothy [1 ]
Danko, Janine R. [1 ]
Tamminga, Cindy [1 ]
Simmons, Monika [1 ]
Wu, Shuenn-Jue [1 ]
Sun, Peifang [1 ]
Kochel, Tadeusz [1 ]
Raviprakash, Kanakatte [1 ]
Hayes, Curtis G. [1 ]
Porter, Kevin R. [1 ]
机构
[1] Naval Med Res Ctr, Viral & Rickettsial Dis Dept, Infect Dis Directorate, Silver Spring, MD 20910 USA
关键词
Dengue; DNA vaccines; Clinical trials; VIRUS NEUTRALIZING ANTIBODIES; RHESUS MACAQUES; IMMUNE-RESPONSES; HEALTHY-ADULTS; AOTUS MONKEYS; IMMUNOGENICITY; CHALLENGE; SAFETY; VOLUNTEERS; PROTECTION;
D O I
10.1016/j.vaccine.2010.11.050
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Candidate dengue DNA vaccine constructs for each dengue serotype were developed by incorporating pre-membrane and envelope genes into a plasmid vector. A Phase 1 clinical trial was performed using the dengue virus serotype-1 (DENV-1) vaccine construct (D1ME(100)). The study was an open-label, dose-escalation, safety and immunogenicity trial involving 22 healthy flavivirus-naive adults assigned to one of two groups. Each group received three intramuscular injections (0, 1, and 5 months) of either a high dose (5.0 mg, n = 12) or a low dose (1.0 mg, n = 10) DNA vaccine using the needle-free Biojector(R) 2000. The most commonly reported solicited signs and symptoms were local mild pain or tenderness (10/22,45%). local mild swelling (6/22, 27%), muscle pain (6/22, 27%) and fatigue (6/22, 27%). Five subjects (41.6%) in the high dose group and none in the low dose group developed detectable anti-dengue neutralizing antibodies. T-cell IFN gamma responses were detected in 50% (4/8) and 83.3% (10/12) of subjects in the low and high dose groups, respectively. The safety profile of the DENV-1 DNA vaccine is acceptable at both doses administered in the study. These results demonstrate a favorable reactogenicity and safety profile of the first in human evaluation of a DENV-1 DNA vaccine. Published by Elsevier Ltd.
引用
收藏
页码:960 / 968
页数:9
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