The Most Promising Ebola Vaccine Has Been Sitting on the Shelf for 15 Years
The Most Promising Ebola Vaccine Has Been Sitting on the Shelf for 15 Years
最具前景的埃博拉疫苗已在实验室“沉睡”了15年
Fever was the first symptom to grip the crab-eating macaques in their high-containment laboratory on an island off Texas after being infected with the newly discovered Bundibugyo strain of ebola. Then came the weight loss, the rectal bleeding and nosebleeds, while scientists in space suits drew blood to see how the monkeys’ immune systems struggled to fight the aggressive virus. 在德克萨斯州外海的一座岛屿上，高等级生物安全实验室里的食蟹猴在感染了新发现的本迪布焦（Bundibugyo）埃博拉病毒株后，首先出现的症状是发烧。随后，它们开始体重下降、直肠出血和流鼻血，而身穿防护服的科学家们则在采集血液，观察猴子的免疫系统如何艰难地对抗这种极具侵略性的病毒。
But the three monkeys that had received a newly developed vaccine to protect against the understudied strain showed no symptoms of the disease, which eventually killed two-thirds of their unvaccinated companions. 然而，那三只接种了针对这种研究较少的病毒株而研发的新疫苗的猴子，却没有任何患病症状；而它们那些未接种疫苗的同伴中，有三分之二最终死于该病毒。
It was 2011, and virologist Thomas Geisbert’s work developing the vaccine was done. If the vaccine had protected primates from the Bundibugyo strain of ebola, it was highly likely to protect humans. Yet with an outbreak now raging in the Democratic Republic of Congo and Uganda, Geisbert’s promising vaccine hasn’t been deployed at all—or even put through human trials—because there hasn’t been the funding or interest. 那是2011年，病毒学家托马斯·盖斯伯特（Thomas Geisbert）的疫苗研发工作已经完成。如果该疫苗能保护灵长类动物免受本迪布焦埃博拉病毒的侵害，那么它极有可能同样能保护人类。然而，随着疫情在刚果民主共和国和乌干达肆虐，盖斯伯特这款极具前景的疫苗却完全没有被部署，甚至连人体试验都未进行，原因仅仅是缺乏资金和关注。
And it could take months to test its safety and efficacy, even as the Bundibugyo virus causes widespread suffering. “We’ve got the rVSV Bundibugyo vaccine sitting on the shelf,” says Geisbert, an immunology professor at the University of Texas Medical Branch in Galveston. Recombinant vesicular stomatitis virus “rVSV” vaccines use a harmless version of that virus to deliver the genetic instructions needed for the body to fight the disease. 尽管本迪布焦病毒正在造成广泛的痛苦，但测试其安全性和有效性仍可能需要数月时间。“我们的 rVSV 本迪布焦疫苗正躺在架子上，”加尔维斯顿德克萨斯大学医学分校的免疫学教授盖斯伯特说道。重组水泡性口炎病毒（rVSV）疫苗利用该病毒的无害版本，将人体对抗疾病所需的遗传指令输送到体内。
Hundreds of people have been infected in the current outbreak in Central and East Africa, and around 200 have died. Public health officials have been scrambling to develop a vaccine, with the World Health Organization identifying Geisbert’s as the most promising candidate. 在中非和东非当前的疫情中，已有数百人感染，约200人死亡。公共卫生官员一直在争分夺秒地开发疫苗，世界卫生组织已将盖斯伯特的疫苗确定为最有希望的候选疫苗。
Geisbert’s work began in the early 2000s as a defense project focused on other strains of ebola. In the wake of September 11 and concerns that terrorists may deploy ebola and similar pathogens as biological weapons (something the Soviet Union had investigated during the cold war), the US Army provided funding to develop a vaccine for the virus. 盖斯伯特的研究始于21世纪初，最初是一个专注于其他埃博拉病毒株的防御项目。在“9·11”事件后，出于对恐怖分子可能利用埃博拉及类似病原体作为生物武器（苏联在冷战期间曾对此进行过研究）的担忧，美国陆军提供了资金，用于开发针对该病毒的疫苗。
His first big breakthrough in 2003 found monkeys could be protected from ebola with a single injection of the vaccine he had developed. But when Geisbert first published his findings a few years later, he found little commercial interest. 他在2003年取得了第一个重大突破，发现只需注射一剂他研发的疫苗，就能保护猴子免受埃博拉病毒的侵害。但几年后，当盖斯伯特首次发表研究结果时，他发现几乎没有商业兴趣。
“There just wasn’t a global market for an ebola vaccine,” he says. “It’s not a moneymaker, nobody really wanted to pick it up.” “当时埃博拉疫苗根本没有全球市场，”他说。“它不赚钱，没人真的想接手。”
That in part led Geisbert to look at whether this vaccine could protect monkeys from different strains of the disease, which would make it cheaper and easier to develop and mass produce. He tested a blend of vaccines against three of the four ebola viruses known to harm humans with success and published the results in 2009. 这在一定程度上促使盖斯伯特开始研究该疫苗是否能保护猴子免受不同毒株的侵害，因为这样可以降低研发和大规模生产的成本与难度。他成功测试了一种针对四种已知危害人类的埃博拉病毒中的三种的混合疫苗，并于2009年发表了研究结果。
Interest in taking them beyond the lab reached a critical mass during the 2013 to 2016 ebola epidemic, when the Zaire strain—the most common—infected 28,600 people and killed 11,300 in West Africa. The virus’s rapid spread and high mortality rate prompted a race to develop a vaccine. That included one developed by pharmaceutical giant Merck in part thanks to Geisbert’s work. Dubbed Ervebo, it was deployed in a “ring” where contacts of the infected are vaccinated, effectively creating a buffer zone that limited the spread of the virus. 在2013年至2016年的埃博拉疫情期间，将这些疫苗推向实验室之外的兴趣达到了临界点。当时，最常见的扎伊尔（Zaire）毒株在西非感染了28,600人，导致11,300人死亡。病毒的迅速传播和高死亡率引发了一场疫苗研发竞赛。其中包括制药巨头默克公司（Merck）开发的一种疫苗，该疫苗的部分研发得益于盖斯伯特的工作。这种名为 Ervebo 的疫苗被用于“环形”接种，即为感染者的接触者接种疫苗，从而有效地建立了一个限制病毒传播的缓冲区。
The vaccine’s success earned Geisbert a spot among Time magazine’s “ebola fighters,” whom the publication dubbed its people of the year in 2014. 该疫苗的成功使盖斯伯特入选了《时代》周刊的“埃博拉战士”名单，该杂志在2014年将他们评为年度人物。
But Geisbert’s initial study omitted one strain of ebola, Bundibugyo, because it has lower fatality rates and has caused just three outbreaks. That includes a 2012 outbreak that killed 30 people over about three months in the DRC but was contained fairly quickly due to contact tracing and isolation. 但盖斯伯特最初的研究忽略了本迪布焦这一毒株，因为它致死率较低，且此前仅引发过三次疫情。其中包括2012年在刚果民主共和国发生的一场疫情，该疫情在约三个月内造成30人死亡，但由于接触者追踪和隔离措施，疫情很快得到了控制。
“We thought that’s probably the one that’s least likely to pop up,” Geisbert says. “We guessed wrong.” “我们当时认为这可能是最不可能爆发的毒株，”盖斯伯特说。“我们猜错了。”
Concerned by that knowledge gap, in 2011 he decided to modify a vaccine, which led to the crab-eating macaque study. In the same study, he also finally tested a blend of existing ebola vaccines on the Bundibugyo strain, but they didn’t provide 100-percent protection. 出于对这一知识空白的担忧，他在2011年决定改良疫苗，这便有了后来的食蟹猴研究。在同一项研究中，他还最终测试了一种现有埃博拉疫苗的混合物对本迪布焦毒株的效果，但它们未能提供100%的保护。
If the 2012 outbreak had occurred after the major Zaire outbreak, Geisbert says, it’s possible pharmaceutical companies might’ve been more keen to commercialize a vaccine that protects against the Bundibugyo strain. 盖斯伯特表示，如果2012年的疫情发生在扎伊尔大爆发之后，制药公司或许会更有意愿将一种能预防本迪布焦毒株的疫苗商业化。
But with the present outbreak rivaling the 2013 to 2016 one in terms of scale and scope, efforts to play catch-up are going into high gear. Geisbert suspects WHO’s experience with Ervebo is one of the reasons they favor his vaccine candidate, which is basically “Bundibugyo Ervebo,” he says. 但随着当前的疫情在规模和范围上堪比2013年至2016年的那次疫情，追赶性的研发工作正在全速推进。盖斯伯特认为，世卫组织在 Ervebo 上的经验是他们青睐他这款候选疫苗的原因之一，他称这款疫苗基本上就是“本迪布焦版的 Ervebo”。
WHO also noted the success of a similar rVSV-based vaccine targeting the Sudan strain of ebola in a ring vaccination trial in 2025. 世卫组织还注意到，一种针对苏丹埃博拉毒株的类似 rVSV 疫苗在2025年的环形疫苗接种试验中取得了成功。
The rVSV-based Bundibugyo candidate’s suitability for ring vaccination was backed by a 2023 study showing most of the monkeys were protected from the virus even after they were exposed if they had been vaccinated. That is crucial for ring vaccination to work. While the researchers vaccinated the monkeys an unrealistically quick 20 minutes after exposure, the proof of concept sets it apart from Moderna and the University of Oxford’s candidates under development. 这款基于 rVSV 的本迪布焦候选疫苗在环形接种方面的适用性得到了2023一项研究的支持，该研究显示，大多数接种过疫苗的猴子即使在接触病毒后也能得到保护。这对环形接种的有效性至关重要。虽然研究人员在猴子接触病毒后仅20分钟就进行了接种（这在现实中很难实现），但这一概念验证使其区别于莫德纳（Moderna）和牛津大学正在开发的候选疫苗。
“There hasn’t really been much development since that 2023 study, because we weren’t really expecting to see that strain and also because historically it’s been associated with lower-rate mortality as well,” said Courtney Woolsey, the lead author on the paper (Geisbert was a coauthor) and an assistant professor within the University of Texas Medical Branch. “自2023年的研究以来，并没有太多的进展，因为我们并没有真正预料到会出现这种毒株，而且从历史上看，它与较低的死亡率有关，”该论文的第一作者、德克萨斯大学医学分校助理教授考特尼·伍尔西（Courtney Woolsey）说（盖斯伯特是合著者）。
“Nobody really makes money off these vaccines,” she adds, “so there are funding barriers as well to advance these vaccines where people likely aren’t going to make money.” “没有人能真正从这些疫苗中赚钱，”她补充道，“因此，在人们可能无法获利的情况下，推进这些疫苗的研发也存在资金障碍。”
The nonprofit Coalition for Epidemic Preparedness Innovations has offered funding of up to $3.2 million to prepare and start testing the material needed to manufacture Gesbert’s vaccine, which would be the first step towar 非营利组织“流行病防范创新联盟”（CEPI）已提供高达320万美元的资金，用于准备和开始测试生产盖斯伯特疫苗所需的材料，这将是迈向……的第一步。