S2, E01: Infectious Disease and The Rise of Vaccines

 

About this Episode

Since 1796, vaccines have helped humans combat smallpox, the flu, and other infectious diseases. The process of vaccine development has changed drastically since then, and is now front and center in the wake of COVID-19. In the first episode of our series on vaccines, join us as we talk with Dr. Sarah Gould on the history of vaccines and infectious disease.

  • Episode Transcript

    Gina Mullane (00:05):
    Welcome to season two of Vital Science, the podcast where you'll hear real life stories of the human experience of science, as told by researchers, patients, advocates, and people from the Charles River community.

    Gina Mullane (00:18):
    This season, we're talking to leading scientists, who'll share insights into hot topics that are top of mind for our listeners. First up, what everyone's talking about these days, vaccines. We hope you'll tune in for all four episodes, as we first cover vaccine history, and then the immune mechanisms these drugs try to manipulate. Later in the series, our guests will discuss alternatives to vaccine therapy and how organizations are working with the FDA to accelerate development in time for an effective COVID solution.

    Gina Mullane (00:56):
    For our first episode, Vital Science host, Chris Garcia sat down with one of Charles River's principal scientific advisors, Dr. Sarah Gould, to discuss infectious disease, the history of vaccination and the challenges of developing this class of therapies.

    Chris Garcia (01:12):
    Sarah, welcome to Vital Science. We'd love to hear more about you, your background, how you got here.

    Sarah Gould (01:19):
    Thank you. And thank you for having me. Yeah, it's been a bit of a long journey. I started my working life as a nurse, way back, then went off into research, did a PhD and eventually came working for the pharmaceutical industry, for which I've been working for 25 years. And I spent 15 years working in vaccine development.

    Chris Garcia (01:44):
    Can you start with a brief history of infectious disease, and the human timeline?

    Sarah Gould (01:48):
    Well, I think infectious diseases go back a long way, actually probably since time in beginning. And really we can start from when things were recorded. We know that infectious diseases have been around since the year 1000 in China, and then coming up through the centuries with very many familiar names that you'll know today, like leprosy. People have heard of the plague, there was the small pox, measles. These are going back, in terms of smallpox 1492, where you had a Christopher Columbus who took that over to the US.

    Sarah Gould (02:27):
    Then, you're coming up through time and history into the 1500s. We had, again, some outbreaks of smallpox, particularly in India or whooping cough, then there's been typhoid. So you can see you get the general gist. More modern day, we've seen in the 1800s, flu. So people have heard of the 1918 Spanish flu, before that was the 1889 Russian flu. There was also the Asian flu. And then we started to have a couple of new diseases in 1981 was HIV, in 2003 was SARS. So you can see, we've always been around with infectious diseases.

    Chris Garcia (03:08):
    When did the first vaccine come along?

    Sarah Gould (03:12):
    So the first vaccine, it's difficult to say what was the first vaccine, because I think there were things going on in China, et cetera, which gives some indication that people were dabbling around with a type of vaccination. But really, I think the main one was really Edward Jenner, who was famous for the smallpox vaccine. He noticed that milkmaids who contracted cowpox from cows udders, were protected from smallpox. He was trained as a doctor. And eventually in 1796, he took a cow-ox blister, made a little scratch on the skin of a young eight year old boy called James Phipps, and that really was the beginning of vaccines.

    Chris Garcia (03:59):
    So Sarah, can we start with a basic description of how do vaccines work and do they work against both viruses and bacteria?

    Sarah Gould (04:08):
    Yep, sure. Vaccines work against bacteria and viruses. So we have examples of both. So just to give you an example of some that you will be very well aware of, such as diptheria, or meningococcal bacteria. For viruses, there's obviously smallpox, but there's others like rabies or influenza. So yes, we have an array for both types of infectious diseases. And basically, how do they work? Well, the key way they work is that they trigger an antibody response. I won't go into details, because immunology gets a bit more complicated than that, but that's the basics of how they work.

    Chris Garcia (04:47):
    Understood. And we'll dive deeper into the immune response in our next episode. But for now let's talk a little bit more about creating present day vaccines. Obviously, there are more rules that dictate how they are developed. What can you tell us about that?

    Sarah Gould (05:02):
    So that's a very good question in terms of rules and regulations. Obviously, when Edward Jenner was testing on a small boy, there were no rules and regulations. And as we've developed medicine and vaccines, so rules and regulations have come in, and for very good reasons. So that today we have a number of guidelines, regulatory guidelines, that have been placed, that have been developed throughout the 20th century. Some of them maybe only recently, the 1990s, as we've learned, and as we've developed more vaccines.

    Gina Mullane (05:38):
    Who knows when scientific curiosity around infectious disease began, but we at least know that Edward Jenner developed a theory of protective therapy as early as the 1700s. Eight year old James Phipps survived the first dose of what became the smallpox vaccine, but as the practice of inoculation, or variolation advanced, so did the documentation of best practices and resulting guidelines for protecting patient populations.

    Gina Mullane (06:06):
    At present, regulatory authorities around the world continue to collaborate on defining the requirements for producing safe vaccines. Before being administered to healthy patients, vaccines must demonstrate a determined level of efficacy and safety before they can advance to clinical trials. Collectively, the rules can make vaccine development more challenging, especially in a climate where time is of the essence. In discussing the different types of vaccines, Chris and Sarah further illustrate the complexity of development.

    Chris Garcia (06:43):
    Sarah, what do we need to know about the differences in these types of vaccines? Can you go over those with us?

    Sarah Gould (06:49):
    Yes. I can try to do that. As you say, different types of vaccines, meaning how they're made, really. So some can be what they call attenuated, or inactivated like the flu virus, so they get the virus and they just kill it and chop it up. Or others now, what we're seeing now today is we're a bit we're much cleverer, so we can just isolate what we call the antigen that will specifically trigger off that antibody, make it very specific. So we can isolate that and just use that protein piece, so we don't have to have the whole of the virus or the bacteria. And now of course, some of the modern, what we're seeing with COVID, what's called the MRNS vaccines. So again, another type of technology where in fact that the body is now going to make the protein. And they inject the MRNA, and then the body will make the protein for which then the antibodies will be raised against and target the virus.

    Chris Garcia (07:51):
    And with the different types of vaccines, why aren't all vaccines 100% effective?

    Sarah Gould (07:59):
    That's a very difficult question to ask, because there's lots of components to what makes a vaccine effective. And so, first of all, you will never have 100% effectiveness and you'll never have 100% safety, just in anything. And then it's a case of effectiveness being, are we talking at the community level? Are we talking at the individual level? So it can be related to the population. So the age, the person who's receiving it, that can impact, it can relate to when you get exposed to that vaccination, it can relate to the genetic makeup of somebody, there's also herd protection or immunity that comes into it. So there's a number of factors that play a part in the effectiveness of a vaccine, it's just not one variable.

    Chris Garcia (08:58):
    So can we go over, what are the current testing methods for that initial vaccine development?

    Sarah Gould (09:05):
    So the initial testing methods were really in terms of, we can divide those into what's called efficacy. Does the vaccine work? Obviously we're very interested in safety. So safety's very important. Those are the key tests that we do. You start off, obviously pre-clinically, either in a test tube, maybe then we do have to use animals and then we're ready to go into humans, having passed a number of key checks and balances to ensure the safety of humans. And that's the most important criteria before you can go into humans, is safety.

    Chris Garcia (09:44):
    And you mentioned COVID. Right now, we're in phase three clinical trials, which they call the efficacy trials. What does that actually entail?

    Sarah Gould (09:56):
    Yes. So, they're looking at efficacy. There'll be looking at safety and the immunogenicity. They'll have various criteria that they'll be looking at, but they'll definitely be looking at that antibody response in the first instance. They'll also be looking at the safety, so looking for adverse events. So we've just seen today that the phase three clinical trial has currently been put on pause, because there's been what's called a reported adverse event, whether that's related to the vaccine or not, we don't know at this point. So again, it's looking at efficacy and safety.

    Chris Garcia (10:38):
    And how successful does a vaccine have to be in one of these studies for it to be considered effective?

    Sarah Gould (10:46):
    What you're looking for in general. And I think it's a movable number, but around 50%, certainly for COVID, is the number that's being considered as appropriate to be effective.

    Chris Garcia (10:59):
    And is there a baseline for the timeline, or how long a vaccine should be effective for?

    Sarah Gould (11:08):
    Well, obviously the longer, the better, and we can hope that that will be the case. And a lot of vaccines are going to be effective for life, but that isn't always the case. And again, it depends on the type of immune response you get from a vaccine, and all sorts of other factors that can implicate as to how effective a vaccine can be.

    Chris Garcia (11:31):
    And there are some vaccines that require boosters. Why is that?

    Sarah Gould (11:38):
    Well, again, that can be, again, due to diminishing immune response, sometimes concerns in the community as well. Maybe again, depends on the type of disease, whether there's a population coming in, or there might be that are unvaccinated. So there can be various reasons as to why you give a booster. But in general, what's trying to be done by the vaccine is to keep disease at bay, or those selected diseases that we have vaccines for at bay. And then it's that balance, to try and vaccinate as many people as possible.

    Chris Garcia (12:13):
    But there are some other diseases like smallpox and polio where the vaccine you could say almost eradicated that disease.

    Sarah Gould (12:21):
    Well, smallpox, yes. And smallpox has been eradicated likely because it's a human disease. Polio, we have eradicated. Now, again, there is more than just one subtype of polio. So we've eliminated, I'd say, nearly polio two, but polio one and three are still around in certain areas.

    Chris Garcia (12:41):
    So a lot of that sounds like it depends on if there's an animal host where it can survive in nature and then reinfect.

    Sarah Gould (12:48):
    Yeah. That certainly plays a role in eradication. So if you have any reservoirs of a particular virus or bacteria, then it's very hard to completely eradicate. But as you can see, we've managed it with smallpox, but some others are going to be very difficult to eradicate totally. But that doesn't mean we can't eliminate them, or certainly reduce. And that's what we've been very effective at, so that there's a number of diseases that we have reduced over time, such as measles, tetanus, mumps, rubella, that we are reducing them and eliminating them.

    Chris Garcia (13:30):
    Sarah, let's talk more about the flu vaccine. And can you explain to us why that is a vaccine that we have to get each and every year?

    Sarah Gould (13:39):
    Yeah, sure. That the flu's are quite complicated in some ways, but basically it's changing all the time. It can change its genetic structure. And there are four key influenza viruses, A, B, C, and D. And particularly influenza A is the one that changes the most. You'll have heard of the H and the N, this is its antigen that it changes. So you'll have heard H1N1, or H3N1. And that's again, because the virus can change genetically. And therefore, we're not necessarily immune to each virus. Plus, often, our immune response maybe isn't as strong. So again, there's that reason for maybe needing yearly vaccination, et cetera.

    Chris Garcia (14:32):
    That brings us back to the concept of herd immunity, which is all over the news these days.

    Sarah Gould (14:37):
    Yeah. Herd immunity is quite important. How to describe it, it's basically to say that you're seeing a decline in the disease, and actually, that decline is greater than the number of people that are actually immunized. So that by immunizing people, is actually protecting the people that aren't immunized, but you need to have a certain number for that to happen. And that's what they mean by herd protection, or herd immunity.

    Sarah Gould (15:07):
    There's not a precise number. Again, it's going to depend on the disease. I have one figure that shows the coverage was... And it was what was called a hep vaccine, that showed that coverage was less than 70% in Gambia, and was sufficient enough to eliminate hep disease. It depends on a lot of the coverage rate and the reproduction number. So it gets a bit complicated. So at the moment, we're too early with COVID to have that. You'd had to have had a lot more people exposed to the virus to have reached herd immunity.

    Gina Mullane (15:46):
    So we know there are proponents of herd immunity, who believe in the body's natural defenses over the power of a vaccine to prevent infection. Yet, as we discussed earlier, vaccines have been proven effective for decades. The question is, how do we know vaccines are truly safe?

    Chris Garcia (16:07):
    And Sarah, how do we guarantee the safety of vaccines?

    Sarah Gould (16:10):
    So I think we have to say, well, safety is never guaranteed in anything, but overall, if we really look at vaccines and all the data that we have on the safety of vaccines, they are very safe. That doesn't mean to say that they don't come without some side effects. Of course there are some side effects, some mainly to do with related to the immune response, often very limited, local reactions.

    Sarah Gould (16:35):
    I think many people who've had a BCG, or for some of them who are old as me may have had smallpox, you've probably got a little scar on your arm. And that was from a local reaction at the site of injection. So you can have that, you get redness, bit of swelling. Some people suffer a little bit more, maybe, runny nose, headache, fever sometimes. Again, typical signs of, you've stimulated the immune response, which actually you want to do.

    Sarah Gould (17:01):
    Now, there can be some cases where you see allergic type reactions, or there's a syndrome called Guillain-Barre syndrome, but it is so not very many. One case per million of Guillain-Barre has been noted. So in terms of, if you look at the risk-benefit overall, there's a lot of benefit and, and limited risk. One of the challenges I think though, that we do have, and particularly in affluent society, is that risk perception changes. And basically they become more risk averse as you become more affluent. And human beings aren't very good at risk assessment and risk perception, so that can be challenging as how people view the risks of vaccines.

    Sarah Gould (17:59):
    Just to give you an example, what's safer, in terms of a plane crashing, or a car crash, well, sometimes because of the numbers that would be killed from a plane crash that is considered worse than a car crash. But actually millions of people are killed in a year compared with, say 2019, you had about 287 fatalities of an airplane crash. But our human brain is challenged at how to look at that risk and how it perceives risks.

    Chris Garcia (18:30):
    Sarah, thanks for bringing your expertise and talking with us today and sharing with our listeners about the history of vaccines and the current development for vaccines now. We really appreciate it.

    Sarah Gould (18:40):
    Well, thank you. Thank you for the questions. I hope the audience found it interesting. Certainly it was an interesting experience for me, so thank you very much.

    Chris Garcia (18:48):
    Thank you.

    Gina Mullane (18:50):
    Thank you for listening to this episode of Vital Science. Join us next month for the second episode in our four-part vaccine series, immune mechanisms, where we will take a further look into the human body's natural protection and how it affects vaccine development.

    Gina Mullane (19:09):
    Do you have a suggestion, episode idea, or a great story to tell? Contact us at [email protected] Be sure to find us on Apple Podcasts, Stitcher, or wherever you get your podcasts. You can also visit us at Criver.com/vital-science-podcast. Also, be sure to check out our sister podcast Sounds of Science, focusing on innovation and trends in the life science industry. Thanks for listening to this episode of Vital Science. I'm Gina Mullane Have a great day.

 

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Acknowledgments

Hosted by: Chris Garcia
Narrated by: Gina Mullane

Special thanks to: Dr. Sarah Gould


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