- Moderna has administered the first doses of its mRNA-based HIV vaccine to volunteers in a clinical trial.
- The vaccine delivers instructions to HIV-specific antigens that could potentially induce certain immune responses.
- The development of an HIV vaccine has taken decades, and the mRNA technology may help speed up the process.
使用Moderna的mRNA技术的实验性HIV疫苗的第一批剂量已向1阶段临床试验中的参与者提供announcedlast week.
Thetrial正在与非营利国际艾滋病疫苗倡议（IAVI）合作进行。研究人员正在测试提供HIV特异性抗原指令的基于mRNA的疫苗是否可以诱导某些免疫反应。
These antigens, also known as immunogens, were developed by scientific teams at IAVI and Scripps Research. A“概念验证”审判last year found that one of these immunogens generated the desired immune response — priming the right kinds of B cells — in 97 percent of participants.
该试验将启动免疫原本身传递到细胞中。当前的试验将使用ModernA的mRNA技术来提供免疫原的遗传指示，然后细胞将其用于制造该蛋白质。
此外，研究人员正在测试一个单独的增强免疫原（也通过mRNA平台传递），以查看它是否可以帮助B细胞沿正确的方向进一步成熟。
“We are tremendously excited to be advancing this new direction in HIV vaccine design with Moderna’s mRNA platform,” Dr. Mark Feinberg, president and CEO of IAVI, said in a陈述.
“The search for an HIV vaccine has been long and challenging, and having new tools, in terms of immunogens and platforms, could be the key to making rapid progress toward an urgently needed, effective HIV vaccine.”
新试验部分由Bill＆Melinda Gates基金会, is the first step in the process of guiding the maturation of certain types of B cells.
The ultimate goal is stimulating the development of B cells that can produce broadly neutralizing antibodies that can target a broad range of HIV variants.
An eventual vaccine using this method will likely involve multiple doses given overweeks to years.
Researchers will enroll 56 healthy, HIV-negative adult volunteers in the current clinical trial. Of these, 48 will receive 1 or 2 doses of the priming immunogen vaccine, with 32 also receiving the boosting immunogen vaccine. Eight people will receive only the vaccine for the boosting immunogen.
In addition, researchers will follow participants for 6 months after their last dose to examine their immune responses and monitor for potential safety concerns.
它一直
Since then, researchers have tried to develop an effective vaccine to protect against HIV — with several large-scale phase 3 clinical trials but no real success.
One challenge with developing an HIV vaccine is that once the virus infects a cell, it replicates wildly, so an effective vaccine would need to essentially block all infection.
“If [HIV] gets through to start an infection, even if somebody has been vaccinated, then that infection is life-long,” saidDr. Davey Smith，加州大学圣地亚哥分校的传染病专家和转化研究病毒学家。
甚至连COVID-19疫苗不提供这种of complete protection against infection. However, they still provide strong protection against severe illness, hospitalization, and death.
The bar for an HIV vaccine is higher because of the need to prevent lifelong infection with the virus.
There areeffective HIV medicines这可以减少体内病毒的复制，但并不能完全消除病毒。这些药物可以帮助人们长寿健康的生活，并降低将病毒传播给他人的风险。
Earlier attempts at HIV vaccines focused on inducing the immune system to make neutralizing antibodies that inactivate the virus, such as by preventing it from infecting cells.
但是，艾滋病毒迅速发展以产生新的变体，甚至比流感病毒更多。
每年，季节性
In comparison, one学习估计流感病毒的遗传序列的全球多样性与单一病毒中发现的HIV序列的多样性相媲美。
The wide genetic variation of HIV makes it difficult to target the virus with a vaccine, because neutralizing antibodies generated in response to one vaccine might work only against a few HIV strains.
More recent HIV vaccine research has focused on developing vaccines than can generate broadly neutralizing antibodies that target parts of the virus’ surface that are the same across many strains.
This is the approach being taken by IAVI and Scripps scientists. The challenge lies in finding the best immunogens to guide the maturation of B cells so they will produce these broadly neutralizing antibodies.
Moderna’s mRNA technology may help speed up this process because much of the work of designing the vaccine can be done on a computer.
This ability helped researchers design candidate COVID-19 vaccines within days of Chinese scientists releasing the genetic sequence of SARS-CoV-2, the coronavirus that causes COVID-19.
“We’ve seen promising proof of concept for germline targeting in [last year’s trial], and this trial lets us take that approach to the next stage,”William Schief, PhD, professor at Scripps Research, said in the statement.
他说：“更重要的是，由于现代技术，我们已经能够以非常快的速度加快生产临床试验材料。”
史密斯警告说，不要过度使用当前的研究，尤其是艾滋病毒逃避人体免疫反应的能力，即使是受疫苗刺激的能力。
“It’s a very, very high hill to climb for this new mRNA technology,” he said, “to generate a very broad and potent immune response to protect against HIV.”
尽管如此，他认为这项研究有很多收获。
“They set up these trials very smartly, in my opinion, to learn as much as they can,” he said. “What is the immunogen that makes the immune system really rev up? And what is going to help us protect people in the future from HIV exposures?”
He is also thankful for the renewed interest in finding a vaccine for HIV.
尽管世界卫生组织（WHO）赋予艾滋病毒“流行病”，但许多人认为should be called a “pandemic”由于全世界有数百万人居住在艾滋病毒中。
史密斯说：“我们不应该仅仅因为我们正在与19009年的大流行作斗争，因此不应该放弃最后一次流行病。”“因此，我真的很称赞调查人员研究新技术来提出一种艾滋病毒疫苗，即使经过将近40年的尝试，我们仍然没有得到这种疫苗。”