Antibody-based protection against HIV infection by vectored immunoprophylaxis.
Antibody-based protection against HIV infection by vectored immunoprophylaxis.
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DOI：
10.1038/nature10660
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发表时间：
2011-11-30
期刊：
影响因子：
64.8
通讯作者：
Baltimore, David
中科院分区：
文献类型：
--
作者：
Balazs, Alejandro B.;Chen, Joyce;Hong, Christin M.;Rao, Dinesh S.;Yang, Lili;Baltimore, David
尽管作出了巨大努力，但研制有效的艾滋病毒疫苗仍是一个难以实现的目标。然而，最近，已经鉴定出许多抗体能够中和绝大多数的循环HIV毒株。这些抗体都表现出异常高水平的体细胞突变，推测是由于在持续暴露于进化抗原的过程中广泛的亲和力成熟。虽然大量的努力集中在能够从头引发抗体的免疫原的设计上，这些抗体将靶向相似的表位，但仍然不确定常规疫苗是否能够引发现有广泛中和抗体的类似物。作为免疫的替代方案，载体介导的基因转移可用于将现有的广泛中和抗体分泌到循环中。在这里，我们描述了一个实际的实施这种方法，载体免疫预防（VIP），在小鼠中诱导终身表达这些单克隆抗体在高浓度从一个单一的肌肉注射。这是使用专门的腺相关病毒（AAV）载体实现的，该载体优化用于从肌肉组织生产全长抗体。我们表明，接受VIP的人源化小鼠似乎完全免受HIV感染，即使在静脉注射非常高剂量的复制能力病毒时也是如此。我们的研究结果表明，这种方法的成功翻译人类可能会产生有效的预防艾滋病毒。
Despite tremendous efforts, development of an effective vaccine against HIV has proved an elusive goal. Recently, however, numerous antibodies have been identified that are capable of neutralizing the vast majority of circulating HIV strains. These antibodies all exhibit an unusually high level of somatic mutation, presumably due to extensive affinity maturation over the course of continuous exposure to an evolving antigen. While substantial effort has focused on the design of immunogens capable of eliciting antibodies de novo that would target similar epitopes, it remains uncertain whether a conventional vaccine will be able to elicit analogs of the existing broadly neutralizing antibodies. As an alternative to immunization, vector-mediated gene transfer could be used to engineer secretion of the existing broadly neutralizing antibodies into the circulation. Here we describe a practical implementation of this approach, vectored immunoprophylaxis (VIP), which in mice induces lifelong expression of these monoclonal antibodies at high concentrations from a single intramuscular injection. This is achieved using a specialized adeno-associated virus (AAV) vector optimized for the production of full-length antibody from muscle tissue. We show that humanized mice receiving VIP appear to be fully protected from HIV infection even when challenged intravenously with very high doses of replication-competent virus. Our results suggest that successful translation of this approach to humans may produce effective prophylaxis against HIV.
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影响因子：
56.9
作者：
Haynes, BF;Fleming, J;Alam, SM
通讯作者：
Alam, SM
影响因子：
17.3
作者：
Dormitzer PR;Ulmer JB;Rappuoli R
通讯作者：
Rappuoli R
DOI：
10.1126/science.1213782
发表时间：
2011-12-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Diskin R;Scheid JF;Marcovecchio PM;West AP Jr;Klein F;Gao H;Gnanapragasam PN;Abadir A;Seaman MS;Nussenzweig MC;Bjorkman PJ
通讯作者：
Bjorkman PJ
DOI：
10.1073/pnas.182412299
发表时间：
2002-09-03
影响因子：
11.1
作者：
Gao, GP;Alvira, MR;Wilson, JM
通讯作者：
Wilson, JM
影响因子：
5.4
作者：
ADACHI, A;GENDELMAN, HE;MARTIN, MA
通讯作者：
MARTIN, MA