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espite 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 strains 1, 2, 3, 4, 5. These antibodies all exhibit an unusually high level of somatic mutation 6, presumably owing to extensive affinity maturation over the course of continuous exposure to an evolving antigen 7. Although substantial effort has focused on the design of immunogens capable of eliciting antibodies de novo that would target similar epitopes 8, 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.
【突破:成功实现对艾滋病的终身免疫】Nature:加州科学家利用基于基因疗法的新型接种免疫VIP方法,只需注射一次,就让小鼠获得艾疾病的终身全面免疫。就算向小鼠静脉滴注高浓度病毒也不能使其感染。该方法利用改良腺病毒为载体,其插入了HIV中和抗体的DNA,然后注射到肌肉
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