As US measles cases rise, biotech firms start developing new treatments
As US measles cases rise, biotech firms start developing new treatments
随着美国麻疹病例激增，生物技术公司开始研发新疗法
Up until recently, measles vaccination has been so effective that there’s been little medical or financial incentive to develop treatments for the disease. But as measles cases hit a 35-year high and vaccination rates continue to decline in the US, a handful of biotech companies and academic groups have started working on measles treatments for those infected with the virus as well as vulnerable individuals needing short-term protection. 直到最近，麻疹疫苗的有效性一直非常高，以至于在医学或经济上几乎没有动力去开发针对该疾病的治疗方法。但随着美国麻疹病例创下 35 年来的新高，且疫苗接种率持续下降，少数生物技术公司和学术团体已开始着手研发麻疹疗法，旨在为病毒感染者以及需要短期保护的易感人群提供治疗。
It will likely be years, however, before these countermeasures are available, and it’s even more uncertain if those who refuse vaccines would take such treatments. Fueled by large outbreaks in South Carolina and Utah, the US had already surpassed last year’s 2,289 measles cases, and it’s only July. For comparison, there were just 285 cases in all of 2024. 然而，这些应对措施可能还需要数年时间才能问世，而且那些拒绝接种疫苗的人是否会接受此类治疗，更是充满了不确定性。受南卡罗来纳州和犹他州大规模疫情的影响，美国今年的麻疹病例数已超过了去年的 2,289 例，而现在才仅仅七月。作为对比，2024 年全年的病例数仅为 285 例。
Because measles is so contagious, at least 95 percent of people in a community need to receive both doses of the measles vaccine to protect immunocompromised individuals and infants under 12 months old who are too young to be vaccinated. But measles vaccination rates have dipped well below that in many places across the country. 由于麻疹传染性极强，社区中至少需要 95% 的人接种两剂麻疹疫苗，才能保护免疫功能低下的人群以及 12 个月以下因年龄太小而无法接种疫苗的婴儿。但在美国许多地方，麻疹疫苗接种率已远低于这一水平。
Young children are the most susceptible to severe complications from measles. The virus can cause pneumonia by damaging the respiratory tract lining directly and by suppressing the immune system, leaving them susceptible to bacterial infections. It can also cause deafness and potentially fatal brain damage. 幼儿最容易因麻疹引发严重并发症。该病毒通过直接损伤呼吸道内膜并抑制免疫系统，导致幼儿容易继发细菌感染，从而引发肺炎。它还可能导致耳聋和潜在的致命性脑损伤。
Without a measles-specific treatment, doctors rely on supportive care such as preventing dehydration, managing breathing difficulties, and administering steroids for inflammation. Vitamin A is sometimes given to patients because the virus can deplete levels of it in the body, but the supplement has no effect on the virus itself. 由于缺乏针对麻疹的特效药，医生只能依靠支持性护理，例如预防脱水、处理呼吸困难以及使用类固醇来消炎。有时会给患者补充维生素 A，因为病毒会消耗体内的维生素 A 水平，但这种补充剂对病毒本身没有抑制作用。
“What we’re seeing now as we get a resurgence of measles in communities is a horrible lack of options when somebody gets exposed,” says Michael Mina, an epidemiologist and chief medical officer of Invivyd, a Connecticut-based biotech company. Invivyd is developing a type of therapy for measles known as a monoclonal antibody, which mimics natural antibodies the immune system makes to fight off disease. “随着麻疹在社区中卷土重来，我们现在看到的是，当有人接触到病毒时，竟然缺乏有效的应对手段，这太可怕了，”康涅狄格州生物技术公司 Invivyd 的流行病学家兼首席医疗官迈克尔·米纳（Michael Mina）表示。Invivyd 正在开发一种名为单克隆抗体的麻疹疗法，它能模拟免疫系统为抵御疾病而产生的天然抗体。
Given via IV or injection, monoclonal antibodies were widely used to treat and prevent COVID-19, especially in immunocompromised individuals who didn’t mount a strong immune response to the vaccines. Their protective effects can last up to a few months. Invivyd, which developed a monoclonal antibody for COVID, has been getting inquiries from health care providers about when a similar therapy will be available for measles. 单克隆抗体通过静脉注射或注射给药，曾被广泛用于治疗和预防新冠肺炎（COVID-19），特别是针对那些对疫苗无法产生强烈免疫反应的免疫功能低下人群。其保护作用可持续数月。曾开发过新冠单克隆抗体的 Invivyd 公司，目前不断收到医疗服务提供者的咨询，询问何时能有类似的麻疹疗法问世。
In the event of a local measles outbreak, a monoclonal antibody could provide short-term protection to those at high risk of contracting the virus. Invivyd has not yet tested its measles antibody in humans, but Mina says the company is compiling the data needed for the Food and Drug Administration to sign off on clinical trials. 在局部爆发麻疹疫情时，单克隆抗体可以为高危感染人群提供短期保护。Invivyd 尚未对其麻疹抗体进行人体试验，但米纳表示，公司正在整理所需数据，以供美国食品药品监督管理局（FDA）批准临床试验。
At the La Jolla Institute for Immunology, president and CEO Erica Ollmann Saphire has been trying to understand the human antibody response to measles. In May, Saphire and her team published a study describing human antibodies capable of blocking infection by binding to key sites on the measles virus. An infusion of these antibodies resulted in a 500-fold lower viral load in rodents. 在拉霍亚免疫学研究所（La Jolla Institute for Immunology），总裁兼首席执行官埃里卡·奥尔曼·萨菲尔（Erica Ollmann Saphire）一直致力于研究人类对麻疹的抗体反应。今年五月，萨菲尔及其团队发表了一项研究，描述了人类抗体如何通过结合麻疹病毒的关键位点来阻断感染。在啮齿动物实验中，输入这些抗体后，病毒载量降低了 500 倍。
A key step toward getting these treatments into human trials will be manufacturing monoclonal antibodies at scale, which is a costly and complex process. Clinical trials cost millions of dollars to run, and pharmaceutical partners are usually needed to fund them. But measles treatments could be a hard sell for pharma companies. Drugs for infectious diseases aren’t usually big money-makers because of the sporadic nature of outbreaks and short treatment courses. 将这些疗法推向人体试验的关键一步是实现单克隆抗体的大规模生产，这是一个昂贵且复杂的过程。临床试验的运行成本高达数百万美元，通常需要制药合作伙伴提供资金。但对于制药公司来说，麻疹疗法可能并不好卖。由于疫情爆发具有偶发性且治疗周期短，传染病药物通常不是赚钱的“大头”。
“I think this is a real opportunity to solve a public health problem,” Saphire says. “A tool by which you could prevent or treat disease is still cheaper than managing an outbreak or managing a case of fatal encephalitis in a child.” “我认为这是一个解决公共卫生问题的真正机会，”萨菲尔说。“比起应对疫情爆发或治疗儿童致命性脑炎病例，开发一种能够预防或治疗疾病的工具，成本依然更低。”
Some disease models predict that measles could become endemic in the US in the next 25 years, even at current state-level vaccination rates. Monoclonal antibodies could also be costly for patients and insurers. In early 2022, the US government spent $855 million for 1.7 million doses of Evusheld, a monoclonal antibody treatment authorized for COVID. The medication itself was free to patients, but some people were hit with hundreds of dollars in out-of-pocket costs related to the administration of the drug. 一些疾病模型预测，即使按照目前的州级疫苗接种率，麻疹也可能在未来 25 年内成为美国的流行病。单克隆抗体对患者和保险公司来说也可能非常昂贵。2022 年初，美国政府斥资 8.55 亿美元购买了 170 万剂 Evusheld，这是一种获批用于治疗新冠的单克隆抗体药物。药物本身对患者免费，但一些人仍需支付数百美元与药物给药相关的自付费用。
The monoclonal antibody combination that became Evusheld was created in just 25 days by scientists at Vanderbilt University, which have also discovered potent antibodies for measles. The university has partnered with small biotech firm Saravir Biopharma to continue development. James Crowe, an immunologist and director of the Vanderbilt Center for Antibody Therapeutics who led the COVID work, says the strategy is to use a combination of two monoclonal antibodies to drastically reduce the chances that the measles virus could mutate to evade it. 最终成为 Evusheld 的单克隆抗体组合是由范德比尔特大学（Vanderbilt University）的科学家在短短 25 天内研发出来的，该校目前也已发现了针对麻疹的强效抗体。该大学已与小型生物技术公司 Saravir Biopharma 合作继续开发。曾领导新冠抗体研究的免疫学家、范德比尔特抗体治疗中心主任詹姆斯·克罗（James Crowe）表示，其策略是使用两种单克隆抗体的组合，以大幅降低麻疹病毒通过变异来逃避治疗的可能性。
His group has been systematically making human antibodies against viruses that are most likely to cause future pandemics and happened to be in the middle of the measles work last year when US measles cases intensified. “The antibodies that we have isolated are so potent, they strongly inhibit the virus. We feel for sure they could be formulated as a single, long acting shot,” Crowe says. 他的团队一直在系统性地制造针对最可能引发未来大流行病毒的人类抗体，去年美国麻疹病例激增时，他们恰好正在进行麻疹相关研究。“我们分离出的抗体效力极强，能有效抑制病毒。我们确信它们可以被配制成单剂长效注射液，”克罗说。
Once these monoclonal antibodies are ready for human testing, regulators will need to figure out how to evaluate them in clinical trials. New drugs are typically tested in adults first to make sure they’re safe for children. But complications from measles are more likely to hospitalize children, particularly those who are unvaccinated. Antivirals could also be used as a strategy to tr 一旦这些单克隆抗体准备好进行人体测试，监管机构将需要确定如何在临床试验中对其进行评估。新药通常先在成人身上进行测试，以确保其对儿童是安全的。但麻疹并发症更容易导致儿童住院，尤其是那些未接种疫苗的儿童。抗病毒药物也可以作为一种治疗策略……