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源自减毒活麻疹病毒的重组载体:黄病毒疫苗的潜力。

Recombinant vector derived from live attenuated measles virus: potential for flavivirus vaccines.

作者信息

Brandler Samantha, Tangy Frédéric

机构信息

Viral Genomics and Vaccination Laboratory, CNRS-URA3015, Institut Pasteur, 28 rue du Dr Roux, 75015 Paris, France.

出版信息

Comp Immunol Microbiol Infect Dis. 2008 Mar;31(2-3):271-91. doi: 10.1016/j.cimid.2007.07.012. Epub 2007 Sep 14.

Abstract

The measles vaccine is one of the best vaccines currently available. Over the last 30 years, it has been administered to hundreds of millions of children and has proved to be both effective and safe. This attenuated live virus induces life-long immunity after only one or two injections. It is produced on a large scale, with ease, in many countries and is distributed at low cost. These excellent characteristics led us to consider its use as a pediatric live vector, to simultaneously immunize children or adolescents against measles and other viral infections, such as human immunodeficiency virus (HIV) or flavivirus infections. For this purpose, we have developed a vector derived from the live attenuated Schwarz strain of the measles virus (MV). We have demonstrated the capacity of this vector to strongly and stably express genes encoding proteins from HIV and to induce specific humoral and cellular immune responses in vivo. Importantly, we observed that, at least in animal models, the vector can bypass measles vaccine pre-existing immunity when two doses of recombinant vaccine are administered. Clinical trials are in progress to confirm this observation in immunized adults. We also produced MV vectors expressing proteins from West Nile virus and other flaviviruses, which in the case of West Nile virus, protected against experimental challenge. Recombinant live attenuated MV might be used as bivalent vaccination vector to mass immunize children and adolescents against both measles and flaviviral diseases such as Dengue or Japanese Encephalitis in the developing world.

摘要

麻疹疫苗是目前可用的最佳疫苗之一。在过去30年里,它已接种于数亿儿童,且已证明既有效又安全。这种减毒活病毒只需注射一两次就能诱导终身免疫。它在许多国家都能大规模、轻松地生产,且成本低廉。这些优异特性促使我们考虑将其用作儿科活载体,以便同时为儿童或青少年接种麻疹疫苗及预防其他病毒感染,如人类免疫缺陷病毒(HIV)或黄病毒感染。为此,我们研发了一种源自麻疹病毒(MV)减毒活Schwarz株的载体。我们已证明该载体能够强力且稳定地表达编码HIV蛋白的基因,并在体内诱导特异性体液免疫和细胞免疫反应。重要的是,我们观察到,至少在动物模型中,当接种两剂重组疫苗时,该载体能够绕过麻疹疫苗的既有免疫力。目前正在进行临床试验,以在免疫的成年人中证实这一观察结果。我们还制备了表达西尼罗河病毒和其他黄病毒蛋白的MV载体,就西尼罗河病毒而言,该载体可抵御实验性攻击。重组减毒活MV可用作二价疫苗载体,在发展中世界为儿童和青少年大规模接种疫苗,预防麻疹和黄病毒疾病,如登革热或日本脑炎。

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