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  • [ ♪INTRO ]

  • This episode was filmed on April 30, 2020.

  • If we have more recent episodes about vaccines or COVID-19, they will be linked in the description.

  • You might have heard that the COVID-19 crisis won't truly be under control until we have a vaccine

  • -- though increased testing and effective treatments are gonna go a long way.

  • You might also be hearing that even though scientists are working on a bunch of different

  • vaccines right now, it'll be more than a year until we the public can have one

  • -- and that is a best-case.

  • This is frustrating...so you would not be the only person asking WHY WHY WHY this is.

  • Well, there are good reasons.

  • But to understand them, we first have to understand a bit about how the immune system works.

  • And, like, that's not super simple, but it's also fascinating and weird and going

  • to come in handy on more days than just this one.

  • So listen up.

  • Our immune system has two main prongs: innate and adaptive immunity.

  • But the key player here is the adaptive part.

  • Our adaptive immune system responds to things that make us sick, and remembers them for

  • later so that it can keep us from getting sick a second time.

  • Vaccines aim to jump in, before an infection, to teach the adaptive immune system what an

  • infectious agent, or pathogen, looks like, so we don't get sick with it at all.

  • A vaccine shows your immune system a picture of the scary invader, and then it remembers

  • it as a baddie.

  • It's actually more complicated than that.

  • This is all happening at a molecular level...your

  • immune system can't “seeanything, it doesn't have eyes.

  • So isn't actually responding to the pathogen as a whole, it's noticing and responding

  • to specific proteins found on invaders floating around your body, or, in some cases, on the

  • surface of an already-infected cell.

  • Any protein that your immune system identifies as worthy of action is what we call anantigen.”

  • And the cells that are going to respond when

  • antigens are identified is a type of white blood cell called lymphocytes.

  • Each lymphocyte recognizes a specific antigen through a structure called an antigen receptor.

  • But how can your immune system have an antigen receptor for a protein it's never seen?

  • Well, this is where it gets crazy.

  • It's basically a brute-force guessing game...like a computer program hacking a password: you

  • try a gazillion words until one of them locks in and you can use that password to get into somebody's account.

  • Basically, your body makes /trillions/ of lymphocytes with a bunch of very slightly different receptors.

  • And sooner or later, one of them is likely to eventually lock onto any given bug.

  • And once it does, it immediately explodes in population cloning itself over and over

  • and over again into an army of two types of cells.

  • Some are effector cells that make virus-neutralizing antibodies or kill off infected cells to prevent

  • the virus from replicating -- they're meant to stop the present infection.

  • The other type can hold a grudge for yearsmemory cells that will mount an attack

  • should the pathogen ever infect your body again.

  • The goal of a vaccine is to skip right to that memory part, without causing serious

  • side effects in the patient.

  • But there's more than one way to do that...so there is more than one type of vaccine.

  • And because COVID-19 is a relatively new disease, it's worth trying a little bit of everything

  • to see what actually sticks against the SARS-CoV-2 virus.

  • One option is live attenuated vaccines, which

  • are the first type of vaccines ever discovered.

  • They're still used today for diseases like measles, mumps, rubella, and chicken pox.

  • They contain living virus, but don't worry -- it's been weakened.

  • That's what theattenuatedpart refers to.

  • Attenuated viruses are created by breeding them in an environment that is different from

  • what they encounter in a human being, like in low temperatures or in a different species of animal.

  • When that virus is then given to a human, it still retains the tell-tale antigens of

  • its dangerous ancestor that will produce the right memory immune cells we want.

  • But it has spent so much time adapting to a changed environment that it's not very

  • good at virusing inside a human any more -- so it won't replicate enough to cause disease.

  • One project in the works to produce a live

  • attenuated SARS-CoV-2 vaccine is a joint effort between the Indian Serum Institute and the

  • US-based drug research company Codagenix.

  • It's already undergoing animal testing, and the companies may launch human trials in the fall.

  • Live-attenuated vaccines usually produce strong immunity, and they tend to be one-and-done

  • -- no booster shots.

  • But they also have some drawbacks.

  • They need to be kept at a low temperature and protected from light, which can damage them.

  • That makes them harder to manufacture and distribute.

  • Plus, in patients with a weakened immune system, the attenuated virus will occasionally replicate

  • enough to actually cause an infection or even spread to other people.

  • To solve those problems, scientists developed our second kind of vaccine inactivated vaccines,

  • where the pathogen is killed before it's injected into the human body.

  • There are plenty of inactivated vaccines out there, like the ones used for Hepatitis A and rabies.

  • Inactivated vaccines are /much/ safer for patients with a weakened immune system, but

  • what makes them safer also makes them a little weaker.

  • The killed-off virus doesn't replicate in the body, so however much pathogen you put

  • into the injection, that's all the training that your immune system is going to get!

  • That means multiple doses will be necessary, and with some inactivated vaccines, you may

  • may later need periodic booster shots to kick that immunological memory back into gear.

  • At least four inactivated COVID-19 vaccines are currently in development, two of which,

  • created by a pair of Chinese companies, have already been approved for human trials.

  • Live-attenuated and inactivated vaccines have one thing in common: to make them, you first

  • need to grow a lot of the pathogen in a lab.

  • But that's not always easy, because for some germs, this process is just too expensive,

  • time-consuming or dangerous.

  • Which brings us to subunit vaccines.

  • Subunit vaccines only use /part/ of the pathogen.

  • Researchers choose an antigen that will be likely to provoke an immune response, and

  • then grow it up in bacteria or yeast.

  • That means you only have to grow part of the thing -- which is much easier!

  • But those antigens may not induce immunity by themselvesremember, for that to happen,

  • the lymphocyte with the exact right antigen receptor must randomly come across the exact right antigen.

  • So many subunit vaccines use adjuvants, which

  • are substances that will attract our lymphocytes, usually by inducing some inflammation.

  • And that's because inflammation naturally brings in our immune cells

  • and makes the antigen/lymphocyte meet-cute more likely.

  • We use subunit vaccines for things like HPV or Hepatitis B.

  • Right now, there are dozens of subunit COVID-19 vaccine candidates in the work, and a lot

  • of them are already scheduled for human trials later this year.

  • And multiple other types of COVID-19 vaccines based on even newer technologies are already entering human trials.

  • But if that's the case...why is it going to take so long before one of these is available?

  • How long are we going to have to wait?!

  • No matter the technology, each vaccine needs to go through a trial process before getting

  • approved for human use.

  • That process is time-consuming for a reason, as it establishes both that the vaccine is

  • safe, and that it actually works.

  • So let's walk through vaccine trials!

  • First, in the exploratory stage, scientists looking to develop COVID-19 vaccines identify

  • possible candidates in the lab.

  • Once a promising candidate has been discovered, it's time for the preclinical stage, where

  • the vaccines are tested on cells in culture and in animal models.

  • These animal models are carefully selected based on whether a given animal gets sick

  • in a similar enough way to humans to be scientifically informative.

  • Regular mice which is the main thing we use seem to be relatively immune to COVID-19, so there's also an effort to

  • make them more human-ish in their response to the disease by giving them the human version

  • of a protein the virus uses to invade our cells.

  • But even the genetically-engineered mice we have so far only develop mild symptoms to COVID-19.

  • So researchers have also been using naturally susceptible animals, like Syrian hamsters,

  • Rhesus macaques, and ferrets.

  • Working through this menagerie can take time, even if you identify a candidate vaccine pretty quickly.

  • Once a candidate /does/ succeed in preclinical trials, it can go on to Phase I, II and III human testing.

  • Phase I trials are done on groups of fewer than a hundred volunteers.

  • At this stage, researchers find out whether the vaccine candidate actually produces enough

  • of an immune response in a human being that it makes sense to move forward with a bigger study.

  • These trials both test to see whether there are any serious and significant side effects,

  • and they are also used to establish a safe dose for the vaccine -- though bigger trials

  • will provide more feedback there as well.

  • Phase II trials involve groups of several hundred volunteers and a more sophisticated

  • study protocol with a control group that gets a placebo.

  • Here, scientists learn a lot more about the safety, the right dose, and how those doses

  • will have to be timed out.

  • They also find out about the best way to administer it -- like through a nasal spray or an injection.

  • If all goes well, it's time for Phase III, which involves double-blinded testing on groups

  • of thousands of participants.

  • Having a bigger group makes it possible to rule out dangerous, less common side effects

  • that may have slipped through the cracks in earlier trials.

  • But this is also the first trial that aims to test how effective the vaccine will actually be.

  • Previous trials are looking to see if lymphocytes are responding, but without a placebo and

  • thousands of participants, you can't actually check whether the infection rate actually

  • drops in the group that got the vaccine.

  • So the researchers need to give the vaccine to a lot of people.

  • Then they need to give them, and a placebo control group that didn't get the vaccine,

  • time to be in the world where they might naturally get infected to determine the efficacy of the vaccine.

  • If you make it this far, and it is effective, congrats!

  • A successful Phase III trial means that the vaccine can finally be approved for public use.

  • Normally, it takes a vaccine candidate ten to fifteen years to complete all of these testing phases.

  • Yeah, you heard that right.

  • I mean, think about it: for Phase III alone, you have to recruit /thousands/ of people and keep

  • tabs on all of them to make sure your candidate vaccine is working.

  • It isn't a lack of money or researchers or work...TIME itself is a necessary part of the process.

  • The amazing good news though is that for COVID-19, this process is being accelerated on an unprecedented scale.

  • At the time this video is in production, around a hundred vaccine candidates are already being researched.

  • And only a few months after the first outbreak, many of them have already entered Phase I

  • human trials or will do so very soon.

  • Even with this accelerated pace of development, it takes time to find the correct dose...or

  • doses...to make sure the vaccine will work, and be safe enough for us to tolerate.

  • That's why you hear that one year to eighteen months figure.

  • From there...producing and distributing the vaccine will require a lot of thought and

  • work and also isn't an instantaneous process.

  • Researchers think this is about as fast as we can possibly go.

  • But you might be wondering, like, can't we do anything to speed things up?

  • The answer is yes, but it's really complicated and there are tradeoffs and we've got a

  • whole episode on that coming up soon.

  • But we do also have short-term if not permanent solutions to the problem of COVID-19….things like physical

  • distancing which has already saved...probably millions of lives.

  • And in the slightly longer term, scientists are looking for treatments to help those who

  • are infected, including in the WHO-organized SOLIDARITY megatrial that we talked about

  • in this video appearing up in the corner.

  • A vaccine is our long-term hope, even though we can't be sure when any of these candidates will be ready.

  • The good news is, we have really effective ways of creating new vaccines.

  • So we are pretty hopeful that one of these is going to come through.

  • And if there's a good thing that's coming out of this pandemic, it's unprecedented

  • international cooperation between researchers who want everyone, everywhere to be safe from this disease.

  • It shows that working togetheractually works.

  • Thanks for watching this episode of SciShow.

  • What we do here is only possible with the help of our patrons.

  • Our amazing community gets the chance to interact with members of our team on our patron-only

  • Discord, and there's other neat perks too -- like exclusive bloopers.

  • If you're interested in helping out, check out patreon.com/scishow.

  • [♪OUTRO ]

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