本地测试是更大规模试验的一部分

Host Amber Smith: 锡拉丘兹上州医科大学, New York, 邀请您成为“知情患者”, with the podcast that features experts from Central New York's only academic medical center. I'm your host, Amber Smith.

Kids and teens can help develop a vaccine against Lyme disease that's being studied in a clinical trial available in Syracuse.

My guest, Dr. 克里斯托弗·保利诺(christopher Paolino)领导了这项研究. He's an assistant professor of medicine and of microbiology and immunology at Upstate, 他专门研究莱姆病和其他蜱传疾病. 欢迎回到“见多识广的病人”节目. Paolino.

Kristopher Paolino, MD: It's my pleasure.

Host Amber Smith: 跟我们说说这个实验性疫苗，VLA15. I understand it's made by Pfizer.

Kristopher Paolino, MD: Actually, 它是由欧洲一家名为Valneva的公司生产的, 辉瑞公司和瓦尔内瓦公司早在2009年就达成了协议, I think, 2020 to help co-develop the vaccine and push it through the final stages of development.

Host Amber Smith: So is this a new medication?

Kristopher Paolino, MD: Technically it is. It is based off of the old Lyme vaccine that many people don't remember, that was FDA approved back in, I think it was the late '90s, early 2000s. It's got some subtle changes to the development of the vaccine that make it a little bit different, so technically it is a new vaccine.

Host Amber Smith: How is it designed to work?

Kristopher Paolino, MD: It's interesting. So most vaccines that we receive, we receive the vaccine, 然后我们的身体产生免疫反应, so that if we were to be infected or come in contact with an infection, the antibodies will attack those viruses or bacteria and help prevent the infection from developing. 这就是我们在流感和COVID疫苗中看到的情况.

This is actually a very unique vaccine in the sense that it targets the outer surface protein A, 是在莱姆病细菌上表达的吗, inside the midgut of the tick. 你要做的就是接种疫苗, you develop these antibodies, and then, say you're out walking around, and you go to the park, and you get bit by a tick.

Those antibodies in your blood will be taken up by the tick in the blood meal and inactivate, or prevent, 防止细菌从蜱虫身上传播给你, 所以它更像是一种阻断传播的疫苗, 所以在这个意义上，它绝对是独一无二的.

Host Amber Smith: That is interesting. 现在，它已经被证明是安全有效的了吗?

Kristopher Paolino, MD: Yep. So again, it's similar to the vaccine that we had back in the late '90s, which was shown to be effective and overall was felt to be very safe as well. This vaccine has already gone through Phase 1 and Phase 2 studies, 而且它已经处于一个更大的, 第三阶段研究始于2020年8月.

It has been shown to be safe, based on those earlier studies, and this major Phase 3 study is going to look to show effectiveness of how well it prevents people from getting Lyme disease.

It did show in the Phase 2 studies that it had a very strong immune response. 所以希望当人们接种这种疫苗时, it will help prevent Lyme cases from developing if you're bitten by a tick.

Host Amber Smith: Now, why is it important to find people age 12 to 17 who are willing to be test subjects for this?

Kristopher Paolino, MD: 只要有新疫苗问世, we always want to make sure that it's safe for all populations. So with the larger Phase 3 study, they are enrolling pediatric populations all the way up through adults.

This study, 这是另一项研究的分支吗, 尽管这是一个完全独立的协议, is a Phase 3 study just looking at the safety in pediatric populations, 所以这项研究将着眼于5到17岁的孩子, 他们会把它分成两组.

There'll be five- and 11-year-olds in one group, and then 12- and 17-year-olds in the other group. And we're basically just going to be collecting data on any side effects, 任何人都可能遇到的不良反应, typically things like arm soreness, redness in the arm, fevers, fatigue, headaches, those kind of things, after vaccination.

Host Amber Smith: Does Lyme disease affect kids the same way that it does adults, potentially?

Kristopher Paolino, MD: It does. 可能会有一些细微的差别. Lyme can affect anybody. 儿童患此病的风险可能略有增加. There have been a few studies to indicate that age ranges between 5 and 9 have a higher peak in number of cases, but overall, anybody can get Lyme.

它们的表现方式可能有所不同. 所以，年龄较小的孩子可能更容易烦躁. 他们可能更容易发烧, potentially more likely to have joint pain or swelling because they may not identify the tick on them until very much later, when they develop the longer symptoms of late disseminated Lyme disease.

Host Amber Smith: So I wanted to ask you to go over what Lyme disease is and the damage it can do. You mentioned some of the, I guess, more common symptoms, the fevers and the joint pain. Are there other telltale signs that people should be on the lookout for?

Kristopher Paolino, MD: Sure. 莱姆病有不同的阶段.

这是早期的局部莱姆病. 这就是大家都知道的靶心皮疹. So, within anywhere between three days and maybe 30 days of a tick bite, 你可能会出现不断扩大的红疹. 它并不总是看起来像靶疹或靶心. It could be just a confluent red rash that develops from the tick bite and usually gets to the size of a softball, or much larger in some cases, 这可能与流感样症状有关, aches and pains, chills, fevers, headaches. 在某些情况下，发烧可能会很高. 然后随着感染的发展, if somebody maybe doesn't have those symptoms or doesn't have the rash initially to recognize Lyme, 他们可以继续发展其他的表现.

Early disseminated cases would include things like heart involvement or Lyme carditis, 它会在心脏哪里引起炎症, can cause heart abnormalities in terms of how well your heart is able to conduct electrical activity. And people can get very slow heart rates that can be potentially life threatening.

Neurologic infections, or Lyme meningitis, otherwise known as neuroborreliosis, is another early disseminated, presentation. 人们会有非常严重的头痛. 他们可能对强光有问题, neck stiffness, as well as all the other typical flu-like illness symptoms that people can develop.

And then there's also late disseminated infections where you can have Lyme arthritis, where you get that joint swelling, joint pain, typically in the knees, but really any joints can be involved in the cases of Lyme arthritis, 这种情况会持续几个月, generally, after the initial tick bite.

Now, on top of that, 这也是一个长期的过程, and the reasons for these symptoms are still kind of up in the air. Some people hypothesize that there's a persistent infection. Some others hypothesize that there's neurologic damage or joint damage or maybe autoimmune development.

有很多不同的原因. There's a lot of data and science that's being done to try to identify that, 但这些病人可能会持续患上慢性疲劳, chronic headaches and migraines. They can have cognitive issues where they feel like they have brain fog. They might have chronic joint pains, numbness and tingling in their hands and their feet. There's a whole variety of symptoms that people can suffer from. So if we can prevent those people from getting Lyme in the first place, I think it'll help with a lot of the suffering that people deal with.

Host Amber Smith: Are you able to diagnose that someone has Lyme with a blood test?

Kristopher Paolino, MD: Yep. That's the way that we diagnose it.

我以前也谈过这个问题. Early in the case of Lyme, the tests are not super helpful. So if you have like a bullseye rash, I generally wouldn't recommend ordering a blood test in this region. I would just treat for Lyme disease because you may only have a positive test in maybe 20% to 40% of those cases because our bodies need time to develop the antibodies, rather than identified in these blood tests to make the diagnosis. The later you get in the infection, 你的身体产生抗体的时间就越多, so by the time somebody has late disseminated infection with joint pains and joint swelling, generally everybody's going to have a positive test at that point, so the longer you've had it, the more severe the disease, 就越有可能产生免疫反应. It's not 100%, but it's close to it.

Host Amber Smith: 这里是纽约州推荐最近最火的赌博软件的“知情患者”播客. I'm your host, Amber Smith.

I'm talking with Dr. Kris Paolino. He's leading a study at Upstate Medical University of an investigational vaccine against Lyme disease, 他正在招募12到17岁的人参加. Anyone who is interested can learn more at 315-464-9869 or by sending an email to trials, that's [email protected]. 现在，你在试验中寻找什么样的人? Ages, genders, races?

Kristopher Paolino, MD: Primarily, we are going to be looking at the 12- to 17-year-old group. 我们没有参与到更年轻的群体中, so it's a smaller cohort of patients that we're going to be identifying and including. So 12- to 17-year-olds, any gender, any race, would be enrolled in the study.

Host Amber Smith: If someone has had Lyme disease before, are they disqualified from participating?

Kristopher Paolino, MD: This is a great question. This is a yes-and-no answer.

如果你被诊断患有莱姆病, of any sort, in the past three months, you are not enrollable in this study, all right? Now if you had a bullseye rash four months ago, then you would be allowed in the study. The people that are definitively not included are people who have those later-onset manifestations of Lyme disease.

如果你被诊断患有莱姆病, the heart involvement, Lyme meningitis or Lyme arthritis, those are typically the Lyme manifestations that are not going to be enrollable.

Host Amber Smith: Are there other things that would disqualify someone from participating?

Kristopher Paolino, MD: 我想任何时候我们在做疫苗研究, we generally don't enroll people who have any immunodeficiencies, 接受癌症治疗的人, 接受过任何形式的器官移植的人, 长期服用类固醇的人, we generally will not enroll those patients if we're going to be checking maybe the immune response down the road.

另一件事可能更重要, just given the timing of the study, 有人在过去四周内被蜱虫咬过吗,我们不会招收这些人.

But if you had a tick bite, say, last year or six months ago, assuming you didn't develop one of those manifestations of Lyme I mentioned, you'd be enrollable in this study.

Host Amber Smith: 你们打算招收多少人? 因为这是几个地点之一?

Kristopher Paolino, MD: Correct, yeah, 所以他们希望在全球范围内注册, for the entire study, about 3,000名5至17岁的儿童.

我们正在努力招收尽可能多的学生. The goal is to try to get this study filled and done and completed as quickly as we can, so we can get that data, so that we can then have Pfizer go ahead with Valneva and try to get that FDA approval as soon as we can.

Host Amber Smith: 每个参与者都能接种疫苗吗?

Kristopher Paolino, MD: Another good question. The answer is no. 这是一项随机对照研究. Most studies that are like that are going to be in a one-to-one ratio, so for every person that comes in, 其中一人将获得安慰剂(无效剂量), used for comparison in testing), one person will get the vaccine. This study is a bit different because it's more of a three-to-one ratio.

如果有四个人来参加这项研究, three of them may get the vaccine, one of them would get the placebo. 所以你很有可能接种疫苗, 但我们要等很久才能知道谁接种了疫苗, much later in the study.

Host Amber Smith: So at the end, after everything's completed, will the people find out whether they got the vaccine or the placebo?

Kristopher Paolino, MD: The protocol does not specify whether or not they're going to unblind people. My guess is that will be the case once the study is completed, but not until then. So people won't probably know if they received the vaccine or not until well after the study is completed and closed, 只是为了避免研究中的偏见, in the data.

Host Amber Smith: What's involved at the visits?

Kristopher Paolino, MD: It's actually pretty straightforward. 会有一个筛选访问，让人们进来, we'll discuss their medical history, tick exposures, things that I had already mentioned in terms of the inclusion/exclusion criteria. And then, if they are found to be eligible for enrollment, we would be able to do the vaccination.

Vaccinations are going to be on multiple different dates throughout the course of the study. 这是第一天的注射, and then there'll be another injection at the two-month mark, a third injection at the six-month mark and then a fourth booster injection at the 18-month mark.

And at each of these injections, you'll receive a vaccination, 但是在这项研究中没有抽血, so people won't be getting those typical tubes of blood taken for any additional testing. And we're primarily just going to be looking at any kind of side effects that people describe to the investigators.

And we'll be collecting that data through the use of an e-diary that people can download on their phone as an app, and they'll fill it out on a frequent basis for the purpose of the study.

Host Amber Smith: So they need to be willing to commit to 18 months, roughly, of time?

Kristopher Paolino, MD: Actually 24 months, so there'll be an additional phone visit at the 24-month mark, and I believe there's also a phone visit at the 12-month mark.

Host Amber Smith: Now, I understand the participants are volunteers, but do they receive any sort of compensation?

Kristopher Paolino, MD: Yep. As of right now, my understanding is that it will be a $100 compensation per visit in the clinic, and that will be for their time, 他们的努力和参与.

Host Amber Smith: 因为这些人都是12到17岁, are they going to need their parents' permission in order to participate?

Kristopher Paolino, MD: 我们会做一个同意和同意程序, so we need consent from both of the parents or legal guardians, as well as, assent, or consent, in a sense, 让病人自己参与进来.

Host Amber Smith: What happens if a study participant gets a tick bite or contracts Lyme disease during the trial?

Kristopher Paolino, MD: That will be something that we will collect and will identify, similar to monitoring for other side effects and other things. 我们想知道是否有人被蜱虫咬了, if they developed Lyme disease or other tick-borne diseases and will collect that data. But they'll be receiving care through their primary care providers.

Host Amber Smith: Do you think that the things you learn from this age group is going to apply to other age groups as well?

Kristopher Paolino, MD: 它会增加正在开发的数据. I think, 从先前的第1期和第2期研究中, 我们从这些试验中获得了很好的数据基础.

I think the big Phase 3 study that's already ongoing is going to be where we're going to see a lot of this data, 而这项额外的研究将会进一步完善它.

Host Amber Smith: Well, Dr. 保利诺，非常感谢你告诉我们这些.

Kristopher Paolino, MD: Thank you for having me.

Host Amber Smith: My guest has been Dr. Kristopher Paolino, an assistant professor of medicine and of microbiology and immunology at Upstate. And for more information about this study, call 315-464-9869 or send an email to [email protected].

我是安珀·史密斯，为您播报纽约州推荐最近最火的赌博软件的“健康连线”节目."