Safety and immunogenicity of attenuated dengue virus vaccines (Aventis Pasteur) in human volunteers
Safety and immunogenicity of attenuated dengue virus vaccines (Aventis Pasteur) in human volunteers
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DOI：
10.1016/s0264-410x(01)00020-2
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发表时间：
2001-04-30
期刊：
影响因子：
5.5
通讯作者：
Hoke, CH
中科院分区：
文献类型：
--
作者：
Kanesa-thasan, N;Sun, W;Hoke, CH
进行了一项随机、对照、双盲研究，以确定安万特巴斯德 (AvP) 生产的五种登革热减毒活疫苗的安全性和免疫原性。该研究由 40 名黄病毒非免疫志愿者完成：五名接受者接种每种单价（登革热-1、登革热-2、登革热-3 或登革热-3）疫苗，十名接受者接受四价（登革热-1、登革热-2、登革热-3 和登革热-3）疫苗，十名接受者仅接种疫苗载体。所有疫苗均以单次皮下剂量施用（范围为 3.6-4.4 log(10) 噬菌斑形成单位）。接种疫苗后6个月的随访中，志愿者未出现严重不良反应。 5 名疫苗接种者在接种后第 8 天至 10 天期间出现发烧（T 大于或等于 38.0 摄氏度），其中包括 4 名四价疫苗接种者。登革热 1、登革热 2、登革热 3 或登革热 4 疫苗接种者报告出现头痛、不适和眼痛等轻度症状的频率相似。四价疫苗接种者在研究第 8-11 天开始出现更温和的症状，并出现分布在躯干和四肢的斑丘疹。接种疫苗后观察到短暂性中性粒细胞减少症（白细胞<4000/mm(3)），但未观察到血小板减少症（血小板<100000/mm(3)）。所有登革热 3、登革热 4 和四价疫苗接种者在第 7 天至第 12 天之间均出现病毒血症，但在登革热 1 或登革热 2 疫苗接种者中很少检测到病毒血症。所有登革热 2、登革热 3 和登革热 4 以及 60% 的登革热 1 疫苗接种者均产生中和抗体和/或免疫球蛋白 M 抗体。 AH 四价疫苗接种者患有登革热 3 病毒病毒血症，并产生了针对登革热 3 病毒的中和抗体。七名志愿者也出现了多价抗体反应，但最高的抗体滴度是针对登革热 3 病毒的。 AvP 登革热病毒减毒活疫苗对人类来说是安全且可耐受的。四价登革热减毒活疫苗的反应原性最强，登革热 3 病毒的优先复制可能影响了其传染性和免疫原性。由爱思唯尔科学有限公司出版
A randomized, controlled, double-blinded study was conducted to determine safety and immunogenicity of five live attenuated dengue vaccines produced by Aventis pasteur (AvP). The study was completed with 40 flavivirus non-immune volunteers: five recipients of each monovalent (dengue-l, dengue-2, dengue-3, or dengue-3) vaccine, ten recipients of tetravalent (dengue-l. dengue-2, dengue-3, and dengue-3) vaccine, and ten recipients of vaccine vehicle alone. All vaccines were administered in a single subcutaneous dose (range, 3.6-4.4 log(10) plaque forming units). No serious adverse reactions occurred in volunteers followed for 6 months after vaccination. Five vaccine recipients developed fever ( T greater than or equal to 38.0 degreesC), including four tetravalent vaccinees between days 8 and 10 after vaccination. Dengue-l, dengue-2, dengue-3, or dengue-4 vaccine recipients reported similar frequency of mild symptoms of headache, malaise, and eye pain. Tetravalent vaccinees noted more moderate symptoms with onset from study days 8-11 and developed maculopapular rashes distributed over trunk and extremities. Transient neutropenia (white blood cells < 4000/mm(3)) was noted after vaccination but not thrombocytopenia (platelets < 100000/mm(3)). All dengue-3, dengue-4, and tetravalent vaccine recipients were viremic between days 7 and 12 but viremia was rarely detected in dengue-l or dengue-2 vaccinees. All dengue-2, dengue-3, and dengue-4, and 60% of dengue-l vaccine recipients developed neutralizing and/or immunoglobulin M antibodies. AH tetravalent vaccine recipients were viremic with dengue-3 virus and developed neutralizing antibodies to dengue-3 virus. Seven volunteers also had multivalent antibody responses, yet the highest antibody titers were against dengue-3 virus. The AvP live attenuated dengue virus vaccines are safe and tolerable in humans. The live attenuated tetravalent dengue vaccine was most reactogenic, and preferential replication of dengue-3 virus may have affected its infectivity and immunogenicity. Published by Elsevier Science Ltd.