Vector-mediated gene transfer engenders long-lived neutralizing activity and protection against SIV infection in monkeys.
Vector-mediated gene transfer engenders long-lived neutralizing activity and protection against SIV infection in monkeys.
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开发艾滋病毒疫苗的圣杯是一种免疫原，它能诱导针对病毒野毒株具有广泛中和活性的持久性抗体。不幸的是，在寻找或设计这种免疫原方面进展甚微。利用SIV模型，我们采取了一种明显不同的方法：将腺相关病毒(AAV)基因转移载体输送到肌肉中，以表达具有预先确定的抗SIV特异性的抗体或抗体样免疫粘附素。通过这种方法，抗SIV分子在肌纤维中内源性合成，并被动分布到循环系统。在猴子身上使用这种方法，我们现在已经在血清中产生了持久的中和活性，并观察到对强毒SIV静脉攻击的完全保护作用。从本质上讲，这一策略绕过了适应性免疫系统，并有望成为一种有效的艾滋病毒疫苗的新方法。
The holy grail for HIV vaccine development is an immunogen that elicits persisting antibodies with broad neutralizing activity against field strains of the virus. Unfortunately, very little progress has been made in finding or designing such immunogens. Using the SIV model, we have taken a markedly different approach: delivery of an adeno-associated virus (AAV) gene transfer vector to muscle for the expression of antibodies or antibody-like immunoadhesins having predetermined anti-SIV specificity. With this approach, anti-SIV molecules are endogenously synthesized in myofibers and passively distributed to the circulatory system. Using such an approach in monkeys, we have now generated long-lasting neutralizing activity in serum and observed complete protection against intravenous challenge with virulent SIV. In essence, this strategy bypasses the adaptive immune system and holds significant promise as a novel approach to an effective HIV vaccine.
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