Clonal vaccinia virus grown in cell culture as a new smallpox vaccine

Clonal vaccinia virus grown in cell culture as a new smallpox vaccine
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DOI:
10.1038/nm916
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发表时间:
2003-09-01
期刊:
影响因子:
82.9
通讯作者:
Monath, TP
Monath, TP
中科院分区:
医学1区
文献类型:
--
作者:
Weltzin, R;Liu, J;Monath, TP

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虽然天花病毒在20多年前就被根除了,但它通过生物恐怖主义的潜在释放重新引起了人们对疫苗接种的兴趣。为了开发一种现代天花疫苗,我们已经改造了来自现有Dryvax疫苗的牛痘病毒,使其在人类二倍体细胞系中生长。我们鉴定了六种克隆和一种未克隆的候选疫苗。基于在小鼠、兔和猴中检测毒力和免疫原性时与Dryvax的可比性,选择一个命名为ACAM1000的克隆进行开发。在大多数情况下,ACAM1000的毒性低于Dryvax。我们在一项随机、双盲人体临床研究中比较了ACAM1000和Dryvax。两种疫苗在产生主要皮肤反应(“takes”)和诱导中和抗体和细胞介导的抗牛痘病毒免疫方面的能力相当。
Although the smallpox virus was eradicated over 20 years ago, its potential release through bioterrorism has generated renewed interest in vaccination. To develop a modern smallpox vaccine, we have adapted vaccinia virus that was derived from the existing Dryvax vaccine for growth in a human diploid cell line. We characterized six cloned and one uncloned vaccine candidates. One clone, designated ACAM1000, was chosen for development based on its comparability to Dryvax when tested in mice, rabbits and monkeys for virulence and immunogenicity. By most measures, ACAM1000 was less virulent than Dryvax. We compared ACAM1000 and Dryvax in a randomized, double-blind human clinical study. The vaccines were equivalent in their ability to produce major cutaneous reactions ('takes') and to induce neutralizing antibody and cell-mediated immunity against vaccinia virus.