Novel directions in HIV-1 vaccines revealed from clinical trials.
Novel directions in HIV-1 vaccines revealed from clinical trials.
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DOI：
10.1097/coh.0b013e3283632c26
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发表时间：
2013-09
影响因子：
4.1
通讯作者：
Russell ND
中科院分区：
文献类型：
--
作者：
Excler JL;Tomaras GD;Russell ND
在过去十年中，开展了大量艾滋病毒-1疫苗开发工作。从长远来看，功效试验的结果和风险相关因素的确定为疫苗开发开辟了巨大的、不可预见的途径。泰国功效试验RV144提供了第一个证据，证明HIV-1疫苗可以防止HIV-1获得。风险相关性分析显示，抗gp120 V2环的IgG抗体与感染风险降低呈负相关，而env特异性IgA抗体与感染风险降低直接相关。进一步的临床试验将集中于测试新的包膜亚基蛋白，这些蛋白由佐剂配制而成，能够诱导更高、更持久的功能性抗体反应（结合抗体和广泛中和抗体）。此外，除了体液反应外，基于载体的疫苗方案还能诱导细胞介导的免疫反应，这仍然是一个优先事项。未来的疗效试验将侧重于预防HIV-1在非洲异性恋人群和亚洲男男性行为者中的传播。最近的成功导致了艾滋病毒-1疫苗开发的新方向，这是疫苗制造商、资助者、科学家和民间社会利益攸关方之间合作和承诺的结果。需要持续和广泛的合作努力，以推进新的疫苗战略，提高效力水平。
Considerable HIV-1 vaccine development efforts have been deployed over the past decade. Put into perspective, the results from efficacy trials and the identification of correlates of risk have opened large and unforeseen avenues for vaccine development. The Thai efficacy trial, RV144, provided the first evidence that HIV-1 vaccine protection against HIV-1 acquisition could be achieved. The correlate of risk analysis showed that IgG antibodies against the gp120 V2 loop inversely correlated with decreased risk of infection, while Env-specific IgA directly correlated with risk. Further clinical trials will focus on testing new envelope subunit proteins formulated with adjuvants capable of inducing higher and more durable functional antibody responses (both binding and broadly neutralizing antibodies). Moreover, vector-based vaccine regimens that can induce cell-mediated immune responses in addition to humoral responses remain a priority. Future efficacy trials will focus on prevention of HIV-1 transmission in heterosexual population in Africa and men who have sex with men in Asia. The recent successes leading to novel directions in HIV-1 vaccine development are a result of collaboration and commitment among vaccine manufacturers, funders, scientists and civil society stakeholders. Sustained and broad collaborative efforts are required to advance new vaccine strategies for higher levels of efficacy.