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《自然》杂志网站11月30日刊登研究报告说,美国研究人员探索出的一种艾滋病基因疗法在动物实验中取得成效。实验证明感染大剂量艾滋病病毒的实验鼠也可受到保护。
Antibody-based protection against HIV infection by vectored immunoprophylaxis
Alejandro B. Balazs, Joyce Chen, Christin M. Hong, Dinesh S. Rao, Lili Yang & David Baltimore
AffiliationsContributionsCorresponding author
Nature (2011) doi:10.1038/nature10660
Received 25 July 2011 Accepted 21 October 2011 Published online 30 November 2011
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Despite tremendous efforts, development of an effective vaccine against human immunodeficiency virus (HIV) has proved an elusive goal. Recently, however, numerous antibodies have been identified that are capable of neutralizing most circulating HIV strains1, 2, 3, 4, 5. These antibodies all exhibit an unusually high level of somatic mutation6, presumably owing to extensive affinity maturation over the course of continuous exposure to an evolving antigen7. Although substantial effort has focused on the design of immunogens capable of eliciting antibodies de novo that would target similar epitopes8, 9, 10, it remains uncertain whether a conventional vaccine will be able to elicit analogues 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, which we call 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 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.
链接:http://www.nature.com/nature/jou ... ll/nature10660.html |
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