WEBVTT - Lab 042: Understanding HIV Part I 0:00:00.720 --> 0:00:04.040 December first was World Aid's Day, and December the entire 0:00:04.080 --> 0:00:06.880 month is HIV Awareness Month. 0:00:06.760 --> 0:00:10.040 And this December is particularly important because it's the fortieth 0:00:10.039 --> 0:00:13.760 anniversary of the first five cases of HIV. 0:00:14.120 --> 0:00:17.640 Wow, forty years feels like not a long time, but 0:00:17.800 --> 0:00:20.079 so much has happened in those forty years. 0:00:20.079 --> 0:00:23.279 It's definitely not a long scientific time, you know, And 0:00:23.360 --> 0:00:26.360 you're right, so much has happened. Even thinking about what 0:00:26.440 --> 0:00:29.880 it meant to have HIV in the eighties and what 0:00:29.920 --> 0:00:32.280 it meant for your life compared to what it means 0:00:32.280 --> 0:00:35.879 now thanks to advances in medicine and vaxine development, all 0:00:35.960 --> 0:00:38.040 kinds of things that are coming along for the treatment 0:00:38.040 --> 0:00:39.360 of HIV and AIDS. 0:00:39.200 --> 0:00:43.240 Right, and our understanding I think of the virus has changed, yes, 0:00:43.440 --> 0:00:46.280 and the way that we interact with people who have 0:00:46.520 --> 0:00:48.440 HIV has changed, thankfully. 0:00:48.640 --> 0:00:51.400 You're right. I think there's so much to unpack even 0:00:51.400 --> 0:00:55.960 though it's a short scientific time. There have been incredible developments, absolutely, 0:00:56.000 --> 0:01:08.319 and I can't wait for us to learn all about it. 0:01:23.240 --> 0:01:27.080 Welcome to Dope Labs, a weekly podcast that mixes hardcore science, 0:01:27.240 --> 0:01:29.319 pop culture, and a healthy dose of friendship. 0:01:29.520 --> 0:01:32.920 This week, we're talking all about HIV Now, HIV has 0:01:32.920 --> 0:01:35.080 been around for a while, and there's been all kinds 0:01:35.080 --> 0:01:37.039 of rumors like, oh, they have a cure and the 0:01:37.080 --> 0:01:39.399 government just doesn't want us to have it. But scientists 0:01:39.440 --> 0:01:41.720 have been working on an HIV vaccine for a pretty 0:01:41.760 --> 0:01:44.640 long time. Yeah, there's a lot swirling around, But what's 0:01:44.760 --> 0:01:47.319 most important is what the science is telling us, and 0:01:47.400 --> 0:01:49.200 that's what we're going to get into today. I just 0:01:49.240 --> 0:01:52.160 saw this story in the Washington Post about an Argentinian 0:01:52.200 --> 0:01:56.080 woman who just became the second person on record whose 0:01:56.120 --> 0:02:00.240 body might have completely eliminated the HIV virus on its own. 0:02:00.440 --> 0:02:02.800 And when something like this happens, it's a huge deal 0:02:02.880 --> 0:02:05.880 for scientists who can study what happened in the patient's 0:02:05.920 --> 0:02:09.040 body and potentially use those findings to develop a cure. 0:02:09.440 --> 0:02:13.639 Let's get into the recitation. 0:02:21.520 --> 0:02:22.320 So what do we know. 0:02:22.639 --> 0:02:25.400 Well, we know HIV stands for the human immuno deficiency 0:02:25.520 --> 0:02:28.200 virus and it's been around for a long time. It's 0:02:28.240 --> 0:02:30.560 been about forty years since the first case of HIV 0:02:30.720 --> 0:02:31.400 was diagnosed. 0:02:31.639 --> 0:02:34.919 We also know that HIV is the virus that causes AIDS, 0:02:34.960 --> 0:02:37.640 so that's similar to how SARS CoV two is the 0:02:37.720 --> 0:02:40.800 virus that can lead to COVID nineteen and HIV affects 0:02:40.800 --> 0:02:41.440 a lot of people. 0:02:41.520 --> 0:02:44.680 So about thirty seven million people worldwide have HIV, and 0:02:45.040 --> 0:02:47.279 about one point two million of those are Americans. 0:02:47.480 --> 0:02:50.040 And we know that HIV is a virus that attacks 0:02:50.040 --> 0:02:52.600 the body's immune system and if it goes untreated, it 0:02:52.600 --> 0:02:55.919 can lead to AIDS. So currently there's no cure for HIV, 0:02:56.040 --> 0:02:58.520 but there are ways to control it through treatment that 0:02:58.600 --> 0:03:01.960 allow those living with HIV to have long, healthy lives. 0:03:02.240 --> 0:03:04.000 So what do we want to know? I think I 0:03:04.040 --> 0:03:08.200 want to know how is the vaccine development for HIV 0:03:08.560 --> 0:03:11.280 different from other types of vaccine development. We've talked about 0:03:11.320 --> 0:03:15.119 vaccine development in previous labs, and so I'm curious if 0:03:15.120 --> 0:03:18.160 it's the same, it's different, and if it's different, how 0:03:18.240 --> 0:03:18.760 is it different? 0:03:18.840 --> 0:03:21.480 And I think before we can even get to vaccine development, 0:03:21.760 --> 0:03:25.519 I need to know some basic biology about HIV. What's 0:03:25.520 --> 0:03:26.959 it looking like, how's it working? 0:03:27.160 --> 0:03:27.320 You know? 0:03:27.320 --> 0:03:28.720 I think we have to kind of understand those things 0:03:28.760 --> 0:03:30.120 before we know how we're going to stop it in 0:03:30.160 --> 0:03:32.200 its tracks. I also want to know the timeline to 0:03:32.240 --> 0:03:34.519 getting here. We didn't just start trying to make a 0:03:34.600 --> 0:03:38.560 vaccine first. There were medicines made available that now feel 0:03:38.600 --> 0:03:41.080 like super medicines compared to what may have seemed possible 0:03:41.120 --> 0:03:43.400 in the eighties. So there are things that can make 0:03:43.600 --> 0:03:47.520 HIV undetectable and thus non transmissible. And why is this 0:03:47.600 --> 0:03:51.560 virus so different from other viruses that it's taken so 0:03:51.920 --> 0:03:54.520 long to develop a vaccine? COVID got us one in 0:03:54.560 --> 0:03:58.200 the vaccine in two years every time, yet hyper speed. 0:03:58.320 --> 0:04:01.480 But this is a very good question. Let's jump into 0:04:01.480 --> 0:04:10.360 the dissection. Our guest for the next two laps is 0:04:10.360 --> 0:04:11.680 doctor Christine Daniels. 0:04:11.720 --> 0:04:14.000 My name is Christine Daniels, and I recently finished my 0:04:14.040 --> 0:04:17.480 post doc at Duke University's Human Vaccine Institute. Christine's work 0:04:17.520 --> 0:04:22.039 focuses on developing and testing novel or new vaccine candidates. 0:04:22.320 --> 0:04:25.680 Christine is another one of me and Zakia's actual friends 0:04:25.680 --> 0:04:27.960 in real life. We always tell you we know some 0:04:28.160 --> 0:04:30.479 very smart people. We all went to Douke at the 0:04:30.560 --> 0:04:34.120 same time, and so you might hear us call her Christine, 0:04:34.360 --> 0:04:41.159 but it is definitely doctor Daniels. Okay, so first things first, 0:04:41.240 --> 0:04:45.280 let's talk about the HIV virus and to understand what 0:04:45.320 --> 0:04:47.360 it is and how it works. We ask doctor Daniels 0:04:47.400 --> 0:04:50.080 to explain it to us in the context of sarskov two, 0:04:50.279 --> 0:04:51.960 the virus that causes COVID nineteen. 0:04:52.200 --> 0:04:55.960 So broadly speaking, HIV and sarskobe two are very similar. 0:04:56.040 --> 0:04:58.760 Let's start with their structure. HIV and sars kov two 0:04:58.880 --> 0:05:00.000 have a pretty similar structure. 0:05:00.160 --> 0:05:01.640 They're both envelope viruses. 0:05:01.839 --> 0:05:04.880 This means that the virus is surrounded by an outer shell. 0:05:05.120 --> 0:05:06.360 They're both expressed. 0:05:06.400 --> 0:05:11.440 Their glycoproteins, or their spike proteins per se on their surface. 0:05:11.160 --> 0:05:13.560 So that envelope or outer shell of the virus is 0:05:13.560 --> 0:05:17.000 covered in these little spikes or proteins, and those proteins 0:05:17.040 --> 0:05:19.800 have little sugars that's the glyco attached to them, and 0:05:19.880 --> 0:05:23.560 those proteins allow the virus to bind or dock onto 0:05:23.600 --> 0:05:25.760 host cells and that leads to infection. 0:05:26.000 --> 0:05:29.760 And HIV and sarscov two are also similar in terms 0:05:29.839 --> 0:05:31.120 of their genetic material. 0:05:31.279 --> 0:05:32.680 They're both RNA viruses. 0:05:32.880 --> 0:05:36.240 This means that they have single stranded RNA or ribonucleic 0:05:36.279 --> 0:05:39.520 acid as their genetic material instead of double stranded DNA 0:05:39.640 --> 0:05:40.479 like human cells have. 0:05:40.880 --> 0:05:45.839 So in each HIV particle, you've got RNA inside surrounded 0:05:45.880 --> 0:05:50.039 by the envelope with a bunch of little spikes all over. 0:05:50.320 --> 0:05:54.240 Called glycoproteins, and so when HIV enters the bloodstream and 0:05:54.320 --> 0:05:56.800 makes contact with the sell those little spikes are attaching 0:05:56.839 --> 0:05:59.159 to the surface and they begin to fuse with the 0:05:59.160 --> 0:06:02.200 host cell. This allows the center of the HIV particle, 0:06:02.200 --> 0:06:04.640 that RNA, to go right into the whole sale and 0:06:04.720 --> 0:06:08.560 to get converted back into DNA. So now you've got 0:06:08.640 --> 0:06:12.160 viral DNA in your wholesale. So from there, the wholesale 0:06:12.240 --> 0:06:15.360 is hijacked by HIV and begins to make more HIV 0:06:15.440 --> 0:06:19.040 particles inside the body. But our body has an amazing 0:06:19.360 --> 0:06:22.359 natural defense when it comes to fighting off viruses, the 0:06:22.400 --> 0:06:25.720 immune system, and when our immune system senses that there 0:06:25.800 --> 0:06:29.120 is an intruder, it can unleash a swarm of targeted 0:06:29.320 --> 0:06:33.360 and general antibodies that will attack the virus, neutralizing it. 0:06:33.520 --> 0:06:35.920 So remember those spikes we talked about covering the outside 0:06:35.960 --> 0:06:40.240 of the virus. Those glycoproteins are what's specifically targeted by antibodies. 0:06:40.440 --> 0:06:45.440 So stars CoV two and HIV viruses are structurally so similar. 0:06:45.600 --> 0:06:48.240 In fact, the decades that have gone into developing the 0:06:48.400 --> 0:06:52.000 HIV vaccine made it possible to develop the COVID vaccine 0:06:52.040 --> 0:06:53.000 so quickly. 0:06:52.960 --> 0:06:56.440 Because they're so structurally similar, we're able to leverage the 0:06:56.480 --> 0:06:59.320 structure based a vaccine platform to design a vaccine for 0:06:59.360 --> 0:07:00.000 COVID nineteen. 0:07:00.120 --> 0:07:03.320 So understanding what the virus looks like structurally, what happens 0:07:03.320 --> 0:07:06.600 when it gets into your body? How are vaccines disrupting 0:07:06.640 --> 0:07:09.159 this process? How do they work? Doctor Daniels gave us 0:07:09.160 --> 0:07:12.640 a great analogy. She thinks of a vaccine like a mugshot. 0:07:12.720 --> 0:07:14.840 The vaccine is going to tell your body, Hey, this 0:07:14.880 --> 0:07:16.960 is who you're looking for. This particle looks like this, 0:07:17.120 --> 0:07:19.600 It has this certain protein on it. When you see it, 0:07:19.720 --> 0:07:30.800 you know what to do. All systems go. 0:07:34.120 --> 0:07:37.240 Now that we know generally how the HIV particle is 0:07:37.320 --> 0:07:41.480 structured and how vaccines work in general, how would an 0:07:41.520 --> 0:07:43.840 effective HIV vaccine work. 0:07:44.080 --> 0:07:47.360 My lab specialized in protein design and expression, so we 0:07:47.480 --> 0:07:49.960 use what we know about how the natural virus is 0:07:50.000 --> 0:07:52.520 structured in its modes of infections in order to design 0:07:52.560 --> 0:07:56.160 synthetic versions of it that mimic the virus but aren't infectious. 0:07:56.320 --> 0:07:58.480 And using what we know, we're able to modify these 0:07:58.480 --> 0:08:01.600 synthetic versions of the virus to help increase the body's 0:08:01.680 --> 0:08:05.400 chances of recognizing them. Basically, instead of trying to redesign 0:08:05.400 --> 0:08:07.760 a fake version of the entire virus. You just take 0:08:07.800 --> 0:08:09.880 the piece of the virus that your body sees and 0:08:09.920 --> 0:08:12.120 develops an immune response against, and that piece of the 0:08:12.280 --> 0:08:15.040 HIV virus that your body sees, that's those spike proteins 0:08:15.040 --> 0:08:17.080 we talked about that are spread out all over the 0:08:17.160 --> 0:08:19.880 envelope of the virus, the glycoproteins. So you have this 0:08:19.920 --> 0:08:22.560 big virus and you have these proteins spiking all over 0:08:22.560 --> 0:08:24.920 the surface. We just take one of those spike proteins 0:08:24.920 --> 0:08:26.280 and we just want to show that to the body 0:08:26.360 --> 0:08:30.040 so the body focuses on the right region. The problem is, though, 0:08:30.120 --> 0:08:32.880 that sometimes just one little piece isn't enough for the 0:08:32.880 --> 0:08:35.959 body to generate a strong immune response. And so what 0:08:36.000 --> 0:08:38.040 you can do is you can attach that piece, so 0:08:38.120 --> 0:08:41.520 that spike that envelope protein onto a nanoparticle and you 0:08:41.520 --> 0:08:43.920 can display multiple copies, so it's kind of like a 0:08:43.920 --> 0:08:46.760 mini virus. And also the NATO particle itself is composed 0:08:46.800 --> 0:08:49.679 of materials that will also activate your immune response. So 0:08:49.720 --> 0:08:52.000 you get a robust immune response because you're showing multiple 0:08:52.000 --> 0:08:54.760 copies of the right target. And then you have something 0:08:54.840 --> 0:08:58.439 else that's stimulating supporting cells to help enhance that immune response. 0:08:58.679 --> 0:09:01.000 All of this is blowing my mind. So doctor Daniels 0:09:01.000 --> 0:09:03.439 works on creating a copy of the envelope of an 0:09:03.559 --> 0:09:07.560 HIV particle covered in those glycoprotein spikes that your body 0:09:07.559 --> 0:09:10.480 will recognize and develop a defense against. And by the way, 0:09:10.600 --> 0:09:14.600 sorry's CoV two vaccines. You know, Maderna, Pfizer, and Johnson 0:09:14.600 --> 0:09:18.360 and Johnson. They may have different strategies, but they all 0:09:18.440 --> 0:09:21.320 are working towards the same goal to help your body 0:09:21.320 --> 0:09:25.440 create a strong immune response against the coronavirus spike protein 0:09:25.600 --> 0:09:27.600 that surrounds the virus. 0:09:27.360 --> 0:09:30.840 And antibodies are one part of that immune response. Antibodies 0:09:30.880 --> 0:09:34.120 are tiny proteins that help your body recognize and clear 0:09:34.320 --> 0:09:37.920 foreign toxins, bacteria, and viral particles. 0:09:38.080 --> 0:09:39.800 So they're like the bouncers outside the club. 0:09:40.160 --> 0:09:45.040 Yes, that's perfect, And Christine mentions neutralizing antibodies And if 0:09:45.080 --> 0:09:49.000 you play on that bouncer metaphor, neutralizing antibodies are binding 0:09:49.040 --> 0:09:51.760 to the outside of a viral particle, so that those 0:09:51.800 --> 0:09:54.199 spike proteins can't bind to any whost sales. So it's 0:09:54.280 --> 0:09:56.880 like if the bouncers make a circle around you, right, 0:09:57.480 --> 0:10:00.600 don't have contact, You're not what I see like when 0:10:00.600 --> 0:10:02.319 they pick you up, when they hold the arms and 0:10:02.360 --> 0:10:04.520 the legs and carry you out the club. That's what 0:10:04.559 --> 0:10:06.000 neutralizing antibodies are doing. 0:10:06.040 --> 0:10:08.600 I've seen that happen to some people. It's pretty embarrassing. 0:10:08.720 --> 0:10:12.360 They say, your evening is over, it's time to retire 0:10:12.440 --> 0:10:13.160 to the boudoir. 0:10:15.520 --> 0:10:18.040 This is really amazing work. Tt It feels like something 0:10:18.200 --> 0:10:21.040 we would do if we had a lab together. Yeah, 0:10:21.160 --> 0:10:23.199 biology with nanoparticles. 0:10:23.320 --> 0:10:24.760 Oh yeah, we'd be all over it. 0:10:24.800 --> 0:10:26.760 Man, this must be really challenging work though. 0:10:27.360 --> 0:10:29.040 Yes, I don't want to pretend like I know how 0:10:29.040 --> 0:10:32.840 to do everything with nanoparticles same, but it sounds so cool. 0:10:33.120 --> 0:10:33.880 I would love this. 0:10:34.120 --> 0:10:35.760 All right, we're going to take a break, but when 0:10:35.800 --> 0:10:37.440 we get back, we're going to talk to doctor Daniels 0:10:37.440 --> 0:10:39.920 about the progress we've made so far towards an effective 0:10:40.040 --> 0:10:42.400 HIV vaccine and how far we have to go. 0:11:01.480 --> 0:11:03.600 We're back and right before we want to break, we 0:11:03.679 --> 0:11:08.559 talked about non neutralizing antibodies, neutralizing antibodies and everything in between. 0:11:08.800 --> 0:11:11.200 But if you want to know more about that, make 0:11:11.240 --> 0:11:13.719 sure that you tune into our episodes in the New Year, 0:11:13.720 --> 0:11:17.200 where we're talking all about the immune system. And before 0:11:17.240 --> 0:11:20.120 we get back to talking about the HIV vaccine Zakia. 0:11:20.200 --> 0:11:21.520 What's on tap next week. 0:11:21.800 --> 0:11:24.720 Next week, we're continuing our conversation with doctor Daniels around 0:11:24.720 --> 0:11:27.880 the development of an effective HIV vaccine, But we're gonna 0:11:27.880 --> 0:11:30.240 shift the lens just a little bit from the science 0:11:30.360 --> 0:11:33.040 to the people, because we know science doesn't happen in 0:11:33.080 --> 0:11:35.720 a vacuum. So we'll be talking through the social context 0:11:35.720 --> 0:11:38.920 around HIV over the past forty years and the people 0:11:38.920 --> 0:11:40.079 who are affected most. 0:11:40.480 --> 0:11:41.920 All right, let's get back to the show. 0:11:43.920 --> 0:11:46.719 So here's what I want to know. We understand the similarities, 0:11:47.040 --> 0:11:49.880 and we understand that work on the HIV vaccine could 0:11:49.920 --> 0:11:53.520 have provided some scaffolding for process and distribution and other 0:11:53.559 --> 0:11:56.360 developments with the COVID nineteen vaccine. But the COVID nineteen 0:11:56.440 --> 0:11:58.760 vaccine got up and running pretty quickly, and we know, 0:11:59.120 --> 0:12:00.760 you know a lot of people we're working on it. 0:12:00.800 --> 0:12:01.240 A lot of. 0:12:01.200 --> 0:12:02.440 Resources were poured into it. 0:12:02.920 --> 0:12:05.640 What's been taking the HIV vaccine, which has been a 0:12:05.640 --> 0:12:08.320 development for many decades, what's been taking it so long? 0:12:08.440 --> 0:12:11.319 So COVID was developed really quickly because it's an easier 0:12:11.360 --> 0:12:13.439 pathogen to design a vaccine against. 0:12:13.480 --> 0:12:17.640 So even though HIV and SARS CoV two are structurally 0:12:17.760 --> 0:12:21.559 similar and are both RNA viruses that use RNA as 0:12:21.600 --> 0:12:25.280 their primary genetic material. A major difference is that SARS 0:12:25.280 --> 0:12:28.440 CoV two doesn't mutate as frequently as HIV. 0:12:29.040 --> 0:12:33.280 HIV mutates incredibly quickly. It can incur about ten mutations 0:12:33.320 --> 0:12:36.400 per replication cycle, and the replication cycle is less than 0:12:36.440 --> 0:12:39.320 twenty four hours. Scientists have estimate that one mutation of 0:12:39.360 --> 0:12:42.680 SARS CoV two is established every eleven days or so. 0:12:42.679 --> 0:12:46.280 So now we're looking at HIV having a mutation rate 0:12:46.320 --> 0:12:49.680 this four times that of sars CoV two. So developing 0:12:49.679 --> 0:12:52.760 a vaccine is able to accommodate all of that variation, 0:12:52.840 --> 0:12:55.600 it's just really hard to do. So the way that 0:12:55.640 --> 0:12:58.440 we try to do that is by designing vaccines that 0:12:58.480 --> 0:13:01.679 are based on the conserved or of the HIV virus, 0:13:01.840 --> 0:13:04.240 and so even if the virus mutates, those are regions 0:13:04.280 --> 0:13:07.600 that don't mutate as frequently, and so if you get 0:13:07.640 --> 0:13:10.000 a response against those sites, then you can likely be 0:13:10.040 --> 0:13:13.600 protected against a wide range of viruses. So that's the approach, 0:13:13.600 --> 0:13:15.600 and that theoretically you know that should work. 0:13:15.760 --> 0:13:19.200 The other challenge for developing an HIV vaccine is the 0:13:19.320 --> 0:13:23.160 length of time of infection. The infection window for sarskov 0:13:23.280 --> 0:13:27.000 two is much shorter than HIV, and like we said before, 0:13:27.240 --> 0:13:31.240 once someone is infected, that person has HIV for life 0:13:31.320 --> 0:13:32.880 with very few exceptions. 0:13:32.960 --> 0:13:36.520 So an HIV infected individual can live with HIV and 0:13:36.559 --> 0:13:38.880 not experience any symptoms for a long time even though 0:13:38.880 --> 0:13:41.760 they're infected with virus and it's infecting a body, and 0:13:41.800 --> 0:13:43.480 not display symptom until they're very sick. 0:13:43.559 --> 0:13:46.480 That also means there's a much longer window for HIV 0:13:46.640 --> 0:13:48.480 to replicate inside your body, so. 0:13:48.440 --> 0:13:51.320 It can mutate, but it's less probable just based on 0:13:51.360 --> 0:13:53.280 that time window and the amount of times that would 0:13:53.320 --> 0:13:55.720 have to replicate in a person within that time window. 0:13:56.000 --> 0:13:59.959 And lastly, HIV is particularly elusive because it's able to 0:14:00.280 --> 0:14:03.600 essentially hide itself from the immune system until it's too late. 0:14:04.080 --> 0:14:08.080 HIV is covered with these sugars called glycans. The glycans 0:14:08.080 --> 0:14:11.240 can attach to the envelope, that hard candy shell of 0:14:11.320 --> 0:14:14.840 the virus and effectively hide the spike proteins from any 0:14:14.920 --> 0:14:17.679 suspecting antibodies. So that's the challenge. 0:14:17.760 --> 0:14:19.960 How do you generate a response that is able to 0:14:20.080 --> 0:14:22.880 learn to bind or obade those black cans to target 0:14:22.920 --> 0:14:23.280 the site. 0:14:23.440 --> 0:14:25.600 That's really tricky because cells in our body naturally have 0:14:25.680 --> 0:14:28.840 glycans all over them, So your immune system isn't going 0:14:28.960 --> 0:14:31.160 to kick in the gear when it sees glycans because 0:14:31.200 --> 0:14:33.600 that would mean you're essentially attacking yourself. 0:14:33.880 --> 0:14:37.240 So in order to generate an effective HIV vaccine, we 0:14:37.280 --> 0:14:39.800 need to figure out a way to generate antibodies that 0:14:39.880 --> 0:14:42.520 are able to bind to the glycans and to the 0:14:42.560 --> 0:14:45.560 protein at the same times. That way they won't be autoreactive. 0:14:45.680 --> 0:14:46.680 And that's just hard to do. 0:14:46.840 --> 0:14:50.360 I have a new appreciation for the challenges associated with 0:14:50.440 --> 0:14:52.120 vaccine design against HIV. 0:14:52.400 --> 0:14:55.360 Right, imagine trying to do a puzzle and every time 0:14:55.520 --> 0:14:57.520 you go to put a piece down, all the pieces 0:14:57.680 --> 0:14:59.000 change their shape. 0:14:58.800 --> 0:15:00.720 Or they're saying you basic, we got to put down 0:15:00.760 --> 0:15:02.640 two pieces at a time glancing in protein. 0:15:02.840 --> 0:15:06.240 Yeah, it's no wonder this vaccine is so hard to develop. 0:15:06.360 --> 0:15:10.440 But you know, vaccines aren't the only line of defense. PREP, 0:15:10.640 --> 0:15:14.000 which is pre exposure prophylaxis, is medicine that people can 0:15:14.040 --> 0:15:17.520 take to prevent getting HIV. So when you take PREP 0:15:17.560 --> 0:15:21.000 as prescribed, it will reduce your risk of contracting HIV 0:15:21.120 --> 0:15:24.800 from sex by about ninety nine percent. That's a huge drop. 0:15:25.080 --> 0:15:28.760 Prep works by setting up fortified walls around the cell 0:15:29.080 --> 0:15:32.760 that HIV is trying to infect, so those spike proteins 0:15:32.880 --> 0:15:35.800 can't bind and infect and as a result of that, 0:15:35.920 --> 0:15:37.960 they can't replicate inside the whole cell. 0:15:38.520 --> 0:15:41.560 It's great because if people take it every day, then 0:15:41.600 --> 0:15:44.760 it reduces their exposure to infection. However, they have to 0:15:44.800 --> 0:15:47.600 take it every day, simply stated. You can think about 0:15:47.600 --> 0:15:50.400 it like something such as birth control. Birth control, like 0:15:50.400 --> 0:15:52.320 if you're taking a pill, it's usually like ninety to 0:15:52.400 --> 0:15:54.840 ninety seven percent effective if you take it according to 0:15:54.920 --> 0:15:57.320 the instructions. The instructions say that you have to take 0:15:57.360 --> 0:16:00.080 the pill at the exact same time every day in 0:16:00.160 --> 0:16:02.360 order for it to reach the efficacy For the people 0:16:02.400 --> 0:16:05.200 that use this type of contraceptive, how many times have 0:16:05.240 --> 0:16:08.000 you not taken it at two two pm every day? 0:16:08.040 --> 0:16:09.240 How many times have you missed a day? 0:16:09.240 --> 0:16:11.320 If you think about vitamins, do you take your vitamins 0:16:11.320 --> 0:16:12.200 every day regularly? 0:16:12.240 --> 0:16:13.800 Do you go to the gym every day regularly? 0:16:13.840 --> 0:16:16.680 All of these behavioral things that we know will positively 0:16:16.680 --> 0:16:19.800 impact our health and our longevity, our quality of life. 0:16:19.880 --> 0:16:21.000 Remember T T shoes? 0:16:24.360 --> 0:16:26.720 Yeah, if you didn't hear the shoe story, go back 0:16:26.720 --> 0:16:28.960 and listen to the lab right before this one. 0:16:28.880 --> 0:16:39.800 Where we talk about, you know, forgetfulness consistency. Taking a 0:16:39.800 --> 0:16:41.440 pill every day for the rest of your life can 0:16:41.480 --> 0:16:43.440 be costly, Like a lot of people might not have 0:16:43.480 --> 0:16:46.680 access to the resources or insurance that allows them to 0:16:46.680 --> 0:16:48.080 get that medication consistently. 0:16:48.360 --> 0:16:50.680 So we need a vaccine because a vaccine will go 0:16:50.680 --> 0:16:53.880 into healthy individuals before they have any potential for exposure 0:16:54.040 --> 0:16:56.280 and prevent them from being infected. You take the full 0:16:56.320 --> 0:16:59.200 regiment of the vaccine, then you're prevented from ever getting 0:16:59.280 --> 0:17:02.080 the virus. And so even if there's a few instances 0:17:02.080 --> 0:17:04.760 of breakthrough, majority of the population will be protected so 0:17:04.760 --> 0:17:07.200 they will never have to do that everyday treatment or 0:17:07.240 --> 0:17:09.919 every day preventative pill. I'm really interested in where we 0:17:09.960 --> 0:17:12.800 are now, as we learn with COVID, getting a vaccine 0:17:12.800 --> 0:17:15.399 approved and on the market can be a very involved, 0:17:15.560 --> 0:17:17.840 expensive and time consuming process. 0:17:17.960 --> 0:17:21.359 Okay, So once a novel or new vaccine candidate is 0:17:21.400 --> 0:17:24.520 developed in a lab, it goes through a really rigorous 0:17:24.560 --> 0:17:28.199 evaluation process where it's tested for safety and effectiveness in 0:17:28.280 --> 0:17:31.760 humans before it's licensed for use. And this includes several 0:17:31.760 --> 0:17:35.119 different phases of clinical trials. You probably remember hearing about 0:17:35.119 --> 0:17:37.679 that with the COVID vaccines too, So we wanted to 0:17:37.720 --> 0:17:40.280 know from doctor Daniels, where are we at in terms 0:17:40.359 --> 0:17:44.560 of progress towards an effective HIV vaccine? Are we close? 0:17:44.960 --> 0:17:47.320 Learning from my predecessors, I'm not going to stay a timeline. 0:17:47.359 --> 0:17:49.879 What I will say is that we are having promising 0:17:50.080 --> 0:17:52.800 results from studies that suggest that we may be on 0:17:52.840 --> 0:17:55.080 the right path. I'm sure it's hard to predict because 0:17:55.160 --> 0:17:58.480 historically the HIV vaccine has been pretty elusive. 0:17:58.640 --> 0:18:01.840 In nineteen eighty four, when HIV was first determined as 0:18:01.880 --> 0:18:04.960 the cause of AIDS, the United States Health and Human 0:18:05.000 --> 0:18:09.119 Services Secretary Margaret Heckler said that she believed a vaccine 0:18:09.119 --> 0:18:11.920 for HIV would be ready for testing in two years. 0:18:12.160 --> 0:18:14.920 There have been multiple trials in different phases through the years. 0:18:15.200 --> 0:18:18.520 Most notably, vax Gen got FDA approval for the first 0:18:18.600 --> 0:18:22.119 large scale Phase three clinical trial of an HIV vaccine 0:18:22.160 --> 0:18:25.480 in nineteen ninety eight. That vaccine was called vax zero 0:18:25.560 --> 0:18:29.400 zero four, but it ultimately failed. For a deep dive 0:18:29.440 --> 0:18:32.000 on that, check out the June second episode of Gimletz 0:18:32.040 --> 0:18:35.159 podcast Not Pasted It, which really breaks it down. 0:18:35.000 --> 0:18:37.080 But there was a clinical trial in two thousand and 0:18:37.160 --> 0:18:38.480 nine with positive results. 0:18:38.800 --> 0:18:41.840 So today the only effective trial has been by the 0:18:42.000 --> 0:18:44.280 r one four to fourth trial that was done in 0:18:44.359 --> 0:18:47.800 humans and it led to about thirty percent protection. 0:18:48.160 --> 0:18:51.199 The RV one forty four trial was a partnership between 0:18:51.320 --> 0:18:54.840 the United States and the Royal Thai governments. From two 0:18:54.880 --> 0:18:57.520 thousand and three to two thousand and six, over sixteen 0:18:57.600 --> 0:19:01.800 thousand people volunteered to receive a two vaccine combination, one 0:19:01.920 --> 0:19:04.639 prime and one boost. When the results were released in 0:19:04.640 --> 0:19:07.600 two thousand and nine, with a thirty two percent efficacy 0:19:07.640 --> 0:19:11.280 rate for preventing HIV, it became the only trial that 0:19:11.320 --> 0:19:14.800 had any evidence of effectiveness and remains so to date. 0:19:15.119 --> 0:19:18.399 You need a much higher efficacy rate to get approval. 0:19:18.680 --> 0:19:22.280 But there were some really valuable learnings from this trial that. 0:19:22.240 --> 0:19:24.280 Enabled us to learn a lot about what type of 0:19:24.320 --> 0:19:26.280 responses are necessary. So that's kind of when we learned 0:19:26.280 --> 0:19:29.000 a lot of information about the fact that neutralizing and 0:19:29.119 --> 0:19:32.199 non neutralizing antibodies contribute to the response. And people have 0:19:32.240 --> 0:19:35.640 followed up on the things that were learned from that 0:19:35.800 --> 0:19:38.880 study in terms of like more recently, there are preliminary 0:19:38.880 --> 0:19:41.639 results from a lab from scripts that show that they 0:19:41.640 --> 0:19:45.000 were able to elicit precursor antibodies that may have that 0:19:45.160 --> 0:19:47.720 breath and potency that we want to listit pre neutralizing 0:19:47.760 --> 0:19:50.919 antibodies and ninety seven percent of their participants, and so 0:19:51.040 --> 0:19:53.840 that's really promising. It's not a final result, you know, 0:19:53.840 --> 0:19:57.159 it's not we elicited neutralizing antibodies, but something that has 0:19:57.200 --> 0:20:00.880 the potential to become a neutralizing antibody. But if that happens, 0:20:01.080 --> 0:20:02.680 then that would jump to the front of the line 0:20:02.680 --> 0:20:03.480 as a candidate. 0:20:08.680 --> 0:20:12.120 So this feels like we are trending in the right direction. 0:20:12.560 --> 0:20:15.840 Yes, all of this information from doctor Daniels has made 0:20:15.880 --> 0:20:18.080 me very excited about the possibilities. 0:20:18.119 --> 0:20:20.440 But I think if we've learned anything over the past 0:20:20.440 --> 0:20:23.639 two years, it is that we are not blank canvases 0:20:23.880 --> 0:20:27.400 for scientific advances, and that it is going to take 0:20:27.520 --> 0:20:32.119 a lot of understanding of social dynamics and just situating 0:20:32.200 --> 0:20:34.960 this research in the context of what's happened before and 0:20:35.000 --> 0:20:35.959 what's happening today. 0:20:36.200 --> 0:20:38.840 Right. I think that is such a great point because 0:20:39.080 --> 0:20:42.480