Attenuation and immunogenicity in humans of a live dengue virus type-4 vaccine candidate with a 30 nucleotide deletion in its 3′-untranslated region
Attenuation and immunogenicity in humans of a live dengue virus type-4 vaccine candidate with a 30 nucleotide deletion in its 3′-untranslated region
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DOI：
10.4269/ajtmh.2001.65.405
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发表时间：
2001-11-01
影响因子：
3.3
通讯作者：
Whitehead, SS
中科院分区：
文献类型：
--
作者：
Durbin, AP;Karron, RA;Whitehead, SS
由于在病毒基因组的3 '-非翻译区中工程化的30个核苷酸缺失，重组登革病毒4型疫苗候选物2A Delta 30在恒河猴中减毒。在20名成人志愿者中进行了一项评价2A Delta 30单次给药安全性和免疫原性的临床试验。候选疫苗耐受性良好，在20名志愿者中没有引起全身性疾病。在14名志愿者中检测到病毒血症，平均水平为1.6 log（10）空斑形成单位/ml血清，尽管所有20名志愿者在接种后第28天血清中和抗体滴度增加7倍或更多（平均滴度= 1：580），但均发生血清转化。10名志愿者出现轻度、无症状性斑疹，5名志愿者出现丙氨酸转氨酶血清水平一过性升高。该候选疫苗的低水平反应原性和高度免疫原性保证了其进一步评价及其用于产生表达1、2和3型登革热病毒结构基因的嵌合疫苗病毒。
The recombinant dengue virus type-4 vaccine candidate 2A Delta 30 was attenuated in rhesus monkeys due to an engineered 30-nucleotide deletion in the 3'-untranslated region of the viral genome. A clinical trial to evaluate the safety and immunogenicity of a single dose of 2A Delta 30 was conducted with 20 adult human volunteers. The vaccine candidate was well tolerated and did not cause systemic illness in any of the 20 volunteers. Viremia was detectable in 14 volunteers at a mean level of 1.6 log(10) plaque-forming units/ml of serum, although all 20 volunteers seroconverted with a seven-fold or greater increase in serum neutralizing antibody titer on day 28 post-vaccination (mean titer = 1:580). A mild, asymptomatic, macular rash developed in 10 volunteers, and a transient elevation in the serum level of alanine aminotransferase was noted in five volunteers. The low level of reactogenicity and high degree of immunogenicity of this vaccine candidate warrant its further evaluation and its use to create chimeric vaccine viruses expressing the structural genes of dengue virus types 1, 2, and 3.