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    RNA vaccines work by delivering genetic material (RNA) that codes for a viral protein to human cells, which then use that code to produce the viral protein and stimulate an immune response. This approach has several advantages over traditional vaccines: it produces more authentic viral proteins, is faster to develop for new viruses, and has a simpler manufacturing process. While RNA vaccine technology has been studied for over a decade, the COVID-19 pandemic provided the motivation and urgency to advance it into widespread clinical use. If proven effective, RNA vaccines could allow for more rapid responses to future outbreaks of new viruses and potentially more effective seasonal flu vaccines.

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    The New Technology Behind COVID-19 RNA Vaccines and What This Means for Future Outbreaks

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    RNA vaccines work by delivering genetic material (RNA) that codes for a viral protein to human cells, which then use that code to produce the viral protein and stimulate an immune response. This approach has several advantages over traditional vaccines: it produces more authentic viral proteins, is faster to develop for new viruses, and has a simpler manufacturing process. While RNA vaccine technology has been studied for over a decade, the COVID-19 pandemic provided the motivation and urgency to advance it into widespread clinical use. If proven effective, RNA vaccines could allow for more rapid responses to future outbreaks of new viruses and potentially more effective seasonal flu vaccines.

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    © All Rights Reserved
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    Download as docx, pdf, or txt
    59 views5 pages

    The New Technology Behind COVID-19 RNA Vaccines and What This Means For Future Outbreaks

    Uploaded by

    Mike Reyes
    RNA vaccines work by delivering genetic material (RNA) that codes for a viral protein to human cells, which then use that code to produce the viral protein and stimulate an immune response. This approach has several advantages over traditional vaccines: it produces more authentic viral proteins, is faster to develop for new viruses, and has a simpler manufacturing process. While RNA vaccine technology has been studied for over a decade, the COVID-19 pandemic provided the motivation and urgency to advance it into widespread clinical use. If proven effective, RNA vaccines could allow for more rapid responses to future outbreaks of new viruses and potentially more effective seasonal flu vaccines.

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    of 5

    The New Technology Behind

    COVID-19 RNA Vaccines and


    What This Means for
    Future Outbreaks
    How RNA Vaccines Will Provide Protection from
    the Virus
    AN INTERVIEW WITH DIANE GRIFFIN | JANUARY 15, 2021

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    Public Health On Call


    This conversation is excerpted from the December 3 episode of Public Health
    On Call.
    Subscribe to Podcast

    In this interview adapted from the December 3, episode of


    Public Health On Call, Stephanie Desmon talks to Johns
    Hopkins immunologist Diane Griffin, MD, PhD, about the
    development of RNA vaccines and how they will provide
    protection from the virus.
    Could you tell us a little about what these RNA vaccines
    are, and why they’re so different from what we’ve seen in
    the past?
    What we want to do with any vaccine is deliver the viral protein that you want the
    person being vaccinated to make an immune response to. There are lots of
    different ways to do that. One is to give the whole virus—inactivated, so it doesn’t
    make the person sick. Another way is to deliver the nucleic acid that encodes the
    protein, and let the [vaccinated person’s] cells actually make the protein.

    RNA is the nucleic acid that codes for proteins that cells make. Basically, it has
    all the information needed to be able to synthesize the protein. The idea of these
    vaccines is that you deliver the RNA that encodes the viral protein you’re
    interested in, and let the cell actually make that protein and to then stimulate the
    immune system.

    What are the benefits of this?


    It has several advantages. Because the cell itself is going to make the protein, it’s
    much more likely to be the native protein, or have the right folding and energetic
    properties of the protein that the virus would also have. Another big advantage is
    that they’re fast to make. If you have the basic platform that [allows you] to insert
    the sequence for your particular protein of interest, you can just take [that] out
    and put another one in. It’s very fast to substitute in a new, different coding
    sequence for a protein.

    Also, the manufacturing turns out to be relatively straightforward for these types
    of vaccines. You don’t have to grow them in cells or do a lot of things that either
    make manufacturing difficult or [require going] through a lot of hoops with the
    FDA to prove that your cells are not contaminated. It bypasses all those steps.

    It has required a fair amount of manipulation of the RNA, because RNA


    intrinsically is unstable. These RNA vaccines have been engineered to make
    them somewhat less likely to be reactogenic, [or likely to] make you sick. The
    RNA also has to be put inside of something. What’s currently being used and has
    turned out to be most successful is what they call a lipid nanoparticle, which
    basically surrounds the RNA that’s going to be the vaccine and does two things:
    First, it protects the RNA from being degraded. Second, it interacts with cells [to
    allow the RNA to enter]. Then the RNA can be released for the cell to actually
    make the protein that you want.
    These are the first RNA vaccines that have gotten this far in
    the process. I guess there was a lot of work done leading
    up to this moment that made it sort of the perfect moment
    to try these. Is that right?
    That’s right. Probably for the last 10 years, people have been working on these
    kinds of vaccines.

    There are two versions. The current two vaccines that we’re dealing with [use]
    just the messenger RNA. There’s also a version [that uses] a self-replicating
    RNA, where it also has the information needed to copy that RNA, so you make
    more copies of it. They’ve been worked on mostly for cancer vaccines. Both self-
    replicating and non-self-replicating RNA have been explored for quite a period of
    time for immunization purposes as well.

    Why were we able to adapt it for the virus that causes


    COVID-19 when they couldn’t really get it into production
    for these other things they’ve tried?
    They have had prototypes for influenza, for rabies, for a number of other
    [viruses], but they’ve never gotten to phase 3 testing. I think maybe the need was
    not so emergent and so critical as it has been here. [COVID-19] has really
    motivated [researchers] to move the technology forward fast. But as you say,
    there’s really been a lot of work that’s been ongoing for the last five to 10 years
    with this platform.

    What’s the potential going forward? Does this mean that


    we will be able to react quickly to things? Does this mean
    perhaps we could create a flu shot that’s more effective?
    I think that we’re very likely to see other vaccines [using this platform]. [SARS-
    CoV-2] came along as a brand-new virus, so it opened the way to apply these
    newer methods. I think there are still questions about how durable this immunity
    is, but yes, I think it’s likely to get applied to more emerging infectious. Where we
    have other new viruses coming on the scene, it may embolden people somewhat
    to try it. And there is work using this platform for influenza vaccines as well.

    Are these generating stronger immune responses than


    traditional vaccines?
    I think they’re good immune responses, but I don’t think they’re necessarily
    better. I think we’ve just been happy that they were good.

    The Pfizer vaccine needs to be stored at -70 degrees


    Celsius, and the Moderna vaccine needs to be stored at -20
    degrees Celsius. Do these vaccines need to be kept cold
    because of the RNA?
    Yes. RNA is unstable at higher temperatures. I think that the Pfizer vaccine can
    withstand a little bit warmer than -70, but it hasn’t been tested or proven. Drug
    companies need to be able to say that they left the vaccine at whatever
    temperature for two weeks and tested it. I think it’s probably been easiest to say,
    “We know it’s OK at this really low temperature, so that’s what we’re going
    to use.”

    For practical reasons, it feels like there’s some urgency for


    Pfizer to find that it can be held not quite that cold.
    Yes, I would imagine. I don’t have any inside information that they’re working on
    that. Because the Moderna vaccine can be stored at a higher temperature—or a
    more reasonable available temperature—[it would seem] that Pfizer will be
    investigating that possibility for their vaccine, as well.

    Not only was this developed quickly, it seems like it can be


    manufactured more quickly.
    Well, it doesn’t require eggs, and it doesn’t require cells. It just requires
    ingredients that you mix together in the manufacturing facility. These vaccines
    have never been manufactured before at large quantities, and scaling up is not
    always as straightforward as just doubling the recipe. So, I think that that is still
    an issue. But the manufacturing facilities anticipated the success of the vaccines,
    and I think both companies have invested in manufacturing facilities, and even
    manufactured the vaccine in advance of getting the data from their trials.

    You’ve been doing this a long time. You must be really


    excited to see a whole new category of vaccine to
    come out.
    I’ve been interested in this technology. We work on measles, and we worked on
    some of the prototype self-replicating vaccines for measles in monkeys. We
    never brought it as far as testing it in people, but they work very well.

    Diane Edmund Griffin, MD, PhD, is a professor in the Department of Molecular


    Microbiology and Immunology at the Johns Hopkins Bloomberg School of Public
    Health.

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