The quest for an HIV-1 vaccine: will mRNA deliver us from evil?
The quest for an HIV-1 vaccine: will mRNA deliver us from evil?
复制标题
对 HIV-1 疫苗的探索：mRNA 能否让我们摆脱邪恶？
DOI：
10.1080/14760584.2023.2184803
复制
发表时间：
2023
影响因子：
6.2
通讯作者：
Lusso,Paolo
中科院分区：
文献类型：
--
作者：
Lusso,Paolo
自从洛杉矶首次报道5例罕见的卡氏肺孢子虫肺炎病例以来，42年过去了，这预示着艾滋病正式出现在世界舞台上，但对HIV-1疫苗的探索仍在进行中，障碍巨大。从抗原变异到聚糖介导的屏蔽再到构象伪装，HIV-1在其非凡的免疫逃避策略方面仍然是无与伦比的。最重要的是，实现保护免受艾滋病毒/艾滋病感染的门槛极高，因为就艾滋病毒-1而言，保护等于“绝育”免疫。原因是，作为一种逆转录病毒，HIV-1将其基因组整合到宿主DNA中，在那里它可以无限期地存活，超出了当前治疗策略的范围。对于大多数其他传染性病原体，疫苗的主要目标是预防原发感染期间发生的急性疾病。对于HIV-1来说，这一目标与保护无关，因为真实的疾病是由适应性免疫系统在几年的慢性感染过程中逐渐退化引起的。一旦病毒进入大门，时间就开始了。除非抗逆转录病毒治疗开始并无限期地持续下去，否则这种疾病几乎必然会发展。因此，对HIV-1疾病免疫的唯一方法是从第一步开始就将病毒锁定在体外：“消灭”免疫。尽管门槛可能很高，但我们现在有令人信服的证据表明，保护性HIV-1疫苗是可行的。这一令人放心的断言是基于两条基本证据：首先，正如从艾滋病毒感染者身上克隆抗体所证明的那样，人类免疫系统有能力产生广泛中和抗体（bNAb），这被广泛认为是保护性疫苗的圣杯;第二，如在非人灵长类动物模型中的被动输注研究所记录的，bNAb可以提供完全的保护，使其免受在其表面上展示HIV-1包膜的嵌合病毒（SHIV）的侵害[2]。但是我们如何才能训练免疫系统产生bNAb呢？这仍然是一个百万美元的问题，迄今为止还没有找到答案。
Forty-two years have gone by since the first report of five unusual cases of Pneumocystis carinii pneumonia in previously healthy young men in Los Angeles [1], which heralded the official appearance of AIDS on the world stage, but the quest for an HIV-1 vaccine is still on. The obstacles have been enormous. HIV-1 remains unrivaled in its extraordinary armamentarium of immune-evasive tactics, spanning from antigenic variation to glycan-mediated shielding to conformational camouflage. Most importantly, the bar to achieve protection from HIV/AIDS is extremely high because, in the case of HIV-1, protection equals ‘sterilizing’immunity. The reason is that, as a retrovirus, HIV-1 integrates its genome into the host DNA where it can survive indefinitely, outside the reach of current therapeutic strategies. For most other infectious agents, the major goal of a vaccine is prevention of the acute illness that occurs during primary infection. For HIV-1 this objective is of no relevance to protection because the real disease is caused by a progressive corruption of the adaptive immune system that occurs over the course of several years of chronic infection. Once the virus gets its foot in the door, the clock starts. And the disease will almost invariably progress unless antiretroviral treatment is initiated and continued indefinitely. Thus, the sole way to immunize against HIV-1 disease is to lock the virus out of the body from square one:‘sterilizing’immunity.As high as the bar may be, we now have convincing evidence that a protective HIV-1 vaccine is feasible. This reassuring assertion is based on two fundamental lines of evidence: first, as documented by antibody cloning from HIV-infected subjects, the human immune system has the ability to produce broadly neutralizing antibodies (bNAbs), which are widely believed to be the Holy Grail for a protective vaccine; second, as documented by passive infusion studies in nonhuman primate models, bNAbs can confer complete protection from chimeric viruses (SHIV) displaying the HIV-1 envelope on their surface [2]. But how can we educate the immune system to produce bNAbs? This remains the million-dollar question that has not, hitherto, found an answer.
影响因子：
158.5
作者：
Jackson, L. A.;Anderson, E. J.;Beigel, J. H.
通讯作者：
Beigel, J. H.