rDEN4Delta30-200,201的I期临床评估：一种旨在降低肝毒性的登革热4型减毒活疫苗候选株
Phase I clinical evaluation of rDEN4Delta30-200,201: a live attenuated dengue 4 vaccine candidate designed for decreased hepatotoxicity.
作者信息
McArthur Julie H, Durbin Anna P, Marron Jennifer A, Wanionek Kimberli A, Thumar Bhavin, Pierro Dennis J, Schmidt Alexander C, Blaney Joseph E, Murphy Brian R, Whitehead Stephen S
机构信息
Center for Immunization Research, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
出版信息
Am J Trop Med Hyg. 2008 Nov;79(5):678-84.
Abstract
The rDEN4Delta30-200,201 is a live attenuated DENV-4 vaccine candidate specifically designed to further attenuate the rDEN4Delta30 parent virus. In the present study, 28 healthy adult volunteers were randomized to receive either 10(5) plaque-forming unit (PFU) of vaccine (20) or placebo (8) as a single subcutaneous injection. Volunteers were evaluated for safety every other day for 16 days. Serum neutralizing antibody titer against DEN4 was determined at study day 28, 42, and 180. The vaccine infected all vaccinees and was well tolerated without inducing alanine aminotransferase (ALT) elevations. Although virus was not recovered from the serum of any vaccinee, moderate levels of neutralizing antibody were induced in all volunteers. Thus the restricted replication of rDEN4Delta30-200,201 previously documented in animal models was confirmed in humans. The rDEN4Delta30-200,201 is a promising candidate and can be considered for inclusion in a tetravalent dengue virus (DENV) vaccine.
摘要
rDEN4Delta30 - 200,201是一种减毒活登革4型疫苗候选株，专门设计用于进一步减弱rDEN4Delta30亲本病毒的毒性。在本研究中，28名健康成年志愿者被随机分为两组，分别接受10(5)个空斑形成单位（PFU）的疫苗（20人）或安慰剂（8人）单次皮下注射。志愿者每隔一天接受16天的安全性评估。在研究第28天、42天和180天测定血清中针对登革4型病毒的中和抗体滴度。该疫苗感染了所有接种者且耐受性良好，未引起丙氨酸转氨酶（ALT）升高。尽管在任何接种者的血清中均未检测到病毒，但所有志愿者均诱导产生了中等水平的中和抗体。因此，先前在动物模型中记录到的rDEN4Delta30 - 200,201的有限复制在人体中得到了证实。rDEN4Delta30 - 200,201是一种有前景的候选疫苗，可以考虑纳入四价登革病毒（DENV）疫苗中。
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