编者按:在全球抗击艾滋病的征途上,HIV疫苗的研发始终是人们关注的焦点。近期,国际艾滋病疫苗行动组织(IAVI)副主席Devin Sok教授在AIDS2024大会上,接受了《感染医线》专访,深入剖析了当前HIV疫苗研发的最新进展与未来展望。Sok教授指出,尽管我们在疫苗研发领域已取得不少成就,但仍处于非常早期阶段,面临着疾病复杂性、人体免疫系统差异性及资源限制等多重挑战。当前研究集中于I期临床试验,评估疫苗安全性与免疫反应。初步数据显示积极效果,但需更多验证。科学家们正不懈努力,未来5-10年或见证新突破。
01
《感染医线》:您对当前HIV疫苗研发的进展如何评价?我们是否正接近实现一个有效且广泛可用的HIV疫苗?
Sok教授:是的,这确实是个非常深刻且值得探讨的问题。在我看来,虽然我们在疫苗研发领域已经取得了不少成就,但实事求是地说,我们仍然处于疫苗研发的非常早期阶段。近年来,针对各种疾病的疫苗研发层出不穷,但其中大多数在有效性试验阶段并未能显示出令人满意的保护效力。这其中的原因复杂多样,包括疾病的复杂性、人体免疫系统的差异性、疫苗设计的挑战性等等。而从实验室的一个初步概念到最终的有效性试验,这中间需要经历无数次的试验、优化和验证,确实是一个漫长且充满挑战的过程。
目前,我们正处于HIV疫苗研究的I期临床试验阶段。这一阶段主要是评估疫苗在人体内的安全性和免疫反应,是疫苗研发过程中非常关键的一步。虽然我们已经取得了一些初步的数据和结果,但仍然需要更多的研究来进一步验证和优化疫苗的效果。
随着科技的不断进步和我们对疾病机制的不断深入了解,将来会有很多机会来加速疫苗研发的过程。我们现在已经在临床试验中测试了很多新的工具、资源和想法,这些都有望为未来的疫苗研发提供新的思路和方向。展望未来,我认为我们将在未来5-10年内证明这些新工具、新资源和新想法的概念,并有望开展下一项有效性试验。
IIDF: Professor Sok, how would you assess the current progress in HIV vaccine development? Are we nearing the realization of an effective and widely available HIV vaccine?
Dr Sok: Yes, that’s a great question. I think realistically we are actually at the very early stages of a vaccine. As you probably know, most of the recent efficacy trials have not shown protective efficacy. It takes a long time to go from a laboratory concept to an efficacy trial. Right now, we are at the phase I clinical trial stage of HIV vaccine research, but I do think there are going to be a lot of opportunities to accelerate. We have a lot of tools, a lot of resources and a lot of good ideas that we are now testing in clinical trials, and I think the pace that we are going to get to proof-of-concept, and the pace that we are going to get to the next efficacy trial is going to be within the next 5-10 years.
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《感染医线》:在您看来,有哪些关键挑战阻碍了HIV疫苗的研发进程?我们如何克服这些挑战?
Sok教授:过去几十年,我们在医学和生物科学领域确实面临了诸多挑战,这些挑战涉及疾病的复杂性、技术的局限性以及资源的匮乏等多个方面。然而,我坚信我们已经克服了许多这些挑战,而SARS-CoV-2疫苗的成功研发就是一个有力的证明。
回顾过去,HIV的研究历程为我们提供了宝贵的经验和教训。从最初确定HIV序列,到最终揭示其详细结构,科学家们历经了长达28年的艰辛探索。这段历程充满了挑战和不确定性,但每一步都为后续的研究奠定了坚实的基础。相比之下,SARS-CoV-2疫苗的研发进程则显得异常迅速。在短短六个月内,我们就取得了突破性的进展,这得益于多个方面的综合因素。其中,HIV领域的研究无疑为我们提供了宝贵的启示和借鉴。通过借鉴HIV疫苗研发的经验和技术,我们能够更加高效地推进SARS-CoV-2疫苗的研发工作。
当然,我们也在不断地克服新的挑战。目前,我认为最大的瓶颈在于资源的限制。尽管我们拥有先进的技术和丰富的知识,但由于资金的匮乏,我们无法更快地推进研究进程。我们需要更多的资金来进行更多的测试,生产更多的突变原,并在更大规模的人群中进行测试以分析结果。这些环节都是加速研究进程的关键所在,但同时也是我们目前面临的最大障碍。
IIDF: What are the key challenges that have hindered the progress of HIV vaccine research in your view? How can we overcome these challenges?
Dr Sok: There are a number of challenges over the last several decades. A lot of them I think we have now overcome, and I think that has been evidenced through the development of the SARS-CoV-2 vaccine, As an example of that, it took 28 years from the identification of the HIV sequence to the discovery of the structure of what HIV looked like. It took six months for SARS-CoV-2. That accelerated timeline for SARS-CoV-2 was thanks to the HIV space. I think a lot of those challenges we are now overcoming. I think the current bottleneck is resources - nowhere to move quickly, needing a lot more money to do more testing, produce more mutagens, and test them in more people to analyze those results. Those are usually the biggest barriers to acceleration.
03
《感染医线》:最近有哪些突破性的研究成果为您对未来HIV疫苗的发展带来了新的希望或方向?
Sok教授:我认为,现在有很多非常令人兴奋的数据,这些数据充分展示了我们在科学研究领域的巨大进步,我希望我在今天的全体会议上已经将这些数据和进展清楚地进行了展示。特别是在临床前研究领域,涌现出了大量振奋人心的数据和突破性的研究成果。
在科学研究中,我们经常会提出各种假设,并通过实验进行验证。然而,很少会出现你先提出一个假设,然后对其进行严格的实验验证,而它竟然真的奏效的情况。绝大多数时候,我们的假设都会因为各种原因而无法成立,或者实验结果与预期存在较大的偏差。但是,现在的情况却有所不同。在过去几年里,我们团队一直在致力于某些创新性的科学研究,提出了一些新的想法和假设。而现在,这些想法和假设竟然真的在实验中得到了验证。我们通过给动物模型(如猕猴)和人类接种疫苗,开展了一系列的疫苗接种研究。在这些研究中,我们不仅看到了预期的结果,还发现了一些超出预期的积极效应。
这些研究进展意味着,我们离实现科学目标又迈进了一步。我们的科学想法正在逐渐变为现实,这不仅令人振奋,也为我们未来的研究提供了更多的可能性和方向。我相信,在未来的日子里,我们将继续取得更多的突破和进展,为人类的健康和福祉做出更大的贡献。因此,我认为这是一个非常激动人心的时刻,它标志着我们的科学探索正在取得实质性的成果,也预示着更多的科学奇迹将在未来诞生。
IIDF: What recent breakthroughs in research have given you new hope or direction for the future development of HIV vaccines?
Dr Sok: I think there is a lot of really exciting data that is coming out right now that I hope I presented clearly in the Plenary today. There is a lot of really exciting data coming out of the preclinical space. Very rarely in science do you have an hypothesis, you test the hypothesis, and it actually works. The vast majority of the time, it never works. But now we are actually seeing ideas that we have had over the past several years, where we are immunizing animal models (macaques) and people, and what we were expecting to see from those vaccination studies, we are in fact seeing. I think it is a really exciting time for all of our scientific ideas actually becoming reality.
04
《感染医线》:在开发HIV疫苗的过程中,我们是否需要考虑不同人群(如儿童、老年人、高风险群体等)的特异性需求?如何确保疫苗对不同人群的有效性?
Sok教授:这个问题触及了我们研究的核心,确实既重要又有趣。正如你所提到的,我们当前正处于I期临床试验的阶段,这意味着我们的研究主要集中在成年人身上。这是因为I期试验主要是为了评估疫苗的安全性和免疫反应,而成年人群体通常被视为最具代表性的试验对象。
然而,我们也意识到,为了更全面地了解疫苗的效果,我们需要将研究范围扩大到更多元化的人群中。这就是我们为什么开始在全球不同地区,包括撒哈拉以南的非洲和其他地区进行试验的原因。我们希望通过比较不同地区的试验结果,来验证疫苗的反应是否一致,以及是否存在地域或人群差异。
国际艾滋病疫苗倡议组织(IAVI)已经在此方面取得了显著进展。我们的G002试验在美国进行,而G003试验则在卢旺达和南非进行。这两项试验的结果都已经出炉,为我们提供了宝贵的数据和洞见。特别值得一提的是,一些初步数据显示,儿童和青少年可能对疫苗产生更好的、更快速的免疫反应。这是一个非常令人振奋的发现,因为如果这一结果得到进一步验证,那么它将极大地加速我们的疫苗研究进程。毕竟,如果我们能够找到一种在儿童和青少年中效果更佳的疫苗,那么我们就可能为更广泛的人群提供更有效的保护。
IIDF: In the development of HIV vaccines, do we need to consider the specific needs of different populations (e.g., children, the elderly, high-risk groups)? How can we ensure the effectiveness of vaccines across these populations?
Dr Sok: That’s a great question. I think it is a really important and interesting question. Because these are phase I trials that we are doing right now, the vast majority of trials are being done in adults. I think the first area for us to diversify with the current work is that most of the trials are being done in the United States. Now we are also doing trials in sub-Saharan Africa and other regions of the world, so we can see whether the responses we are getting across those trials are comparable. IAVI G002 is being done in the United States. IAVI G003 is being done in Rwanda and South Africa. And we have results from those trials now. I think it is going to be really interesting once we reach a stage where we can test other populations. There are some data that children and adolescents could develop better responses, more rapid responses, than adults. If that is true, that can actually help accelerate vaccine research. That is another area of work people are focused on.
05
《感染医线》:展望未来,您认为HIV疫苗的研发将如何与现有的HIV预防和治疗策略相结合,以更有效地控制HIV的传播?
Sok教授:这个问题确实很好。近年来,我们已经充分认识到,能够从HIV预防和治疗服务中受益的人群是极其多种多样的。不同的人群有着不同的需求和生活方式,因此,我们需要提供更加个性化和多样化的服务来满足他们的需求。
HIV疫苗作为预防HIV的重要手段,具有非常具体和独特的目标特征。与其他预防方法相比,疫苗应该能够提供长期、稳定的保护,这是其最大的优势。我们正在努力研发更多不同的预防选择,以适应人们正常生活的多样化需求。这些预防选择将包括不同类型的疫苗、更加便捷的接种方式以及更加个性化的预防策略。
IIDF: Looking ahead, how do you envision HIV vaccine research being integrated with existing HIV prevention and treatment strategies to more effectively control the spread of HIV?
Dr Sok: That’s a great question. I think there is a lot of recognition of the diversity of the population that could benefit from HIV prevention and treatment services. An HIV vaccine has a very specific or different target profile. It should be able to protect for a long duration. You would need to go into the clinic for hopefully three shots to a maximum of five shots, and then you are done. For some individuals who can’t go to the clinic every six months for an injection, or for some individuals who have busy lives, or have other circumstances, an HIV vaccine could really benefit them. That is where having a lot of these different prevention options that can be tailored to how people live their normal lives is going to be really beneficial.