IMMUNIZATION WITH CANARYPOX VIRUS EXPRESSING RABIES GLYCOPROTEIN
IMMUNIZATION WITH CANARYPOX VIRUS EXPRESSING RABIES GLYCOPROTEIN
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DOI：
10.1016/0140-6736(92)92027-d
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发表时间：
1992-06-13
期刊：
影响因子：
168.9
通讯作者：
PLOTKIN, S
中科院分区：
文献类型：
--
作者：
CADOZ, M;STRADY, A;PLOTKIN, S
痘病毒作为携带来自其他病毒的免疫抗原的基因载体具有许多有用的特性，例如易于生产以及能诱导细胞免疫和体液免疫，但人们对痘苗病毒的安全性存在担忧。我们转向一种禽痘病毒（金丝雀痘病毒）；这种病毒在哺乳动物细胞中进行流产性复制，从而能够将早期基因产物呈递给免疫系统。金丝雀痘病毒被用作狂犬病糖蛋白G基因的载体。重组病毒（ALVAC - RG；vCP65）的安全性和有效性在几种动物身上进行了测试，然后进行了一期临床试验。25名志愿者被随机分配接受重组病毒的皮下注射（三组[A、B和C]分别接受两剂10^(3.5)、10^(4.5)和10^(5.5)组织培养感染剂量50）或人二倍体细胞培养疫苗（HDC；每剂6.52国际单位效力）。第二剂接种28天后，所有9名ALVAC - RG的C组受试者以及3名B组受试者中的2名，其狂犬病中和抗体浓度至少为0.5 IU/ml，这是与动物保护相关的水平。尽管此时C组这些抗体的几何平均滴度低于10名HDC接种者（4.4[范围0.9 - 12.5]对比11.5[4.7 - 25.3]IU/ml），但在6个月时的单次加强剂量在接种任何一种疫苗的志愿者中都引发了回忆反应。与ALVAC - RG相关的副作用轻微且持续时间短，其发生频率与HDC疫苗相似。这项研究表明了非复制型痘病毒作为人类疫苗接种载体的潜力。需要对更高剂量以及通过其他给药途径的金丝雀痘病毒重组体进行试验。
Poxviruses have many useful features as vectors for genes that carry immunising antigens from other viruses, such as ease of production and induction of cellular and humoral immunity, but there is concern about the safety of vaccinia virus. We turned to an avian poxvirus (canarypox); this virus undergoes abortive replication in mammalian cells that enables presentation of early gene products to the immune system. Canarypox virus was used as a vector for the rabies glycoprotein G gene.The safety and efficacy of the recombinant (ALVAC-RG; vCP65) were tested in several animal species, then it was subjected to a phase 1 clinical trial. Twenty-five volunteers were randomly assigned to subcutaneous injections of the recombinant (three groups [A, B, and C] received two doses each of 10(3.5), 10(4.5), and 10(5.5) tissue-culture infectious doses50, respectively) or of human diploid cell culture vaccine (HDC; 6.52 international potency units per dose). 28 days after the second dose, all nine ALVAC-RG group-C subjects and two of three group-B subjects had rabies neutralising antibody concentrations of at least 0.5 IU/ml, the level associated with protection in animals. Although the geometric mean titre of these antibodies at that time was lower in group C than in the ten HDC recipients (4.4 [range 0.9-12.5] vs 11.5 [4.7-25.3] IU/ml), a single booster dose at 6 months induced a recall response in volunteers primed with either vaccine. Side-effects associated with ALVAC-RG were mild and of short duration and occurred at similar frequency to those of HDC vaccine.This study has shown the potential of non-replicating poxviruses as vectors for vaccination in human beings. Trials of canarypox-virus recombinants at higher doses and by other routes of administration are needed.