Edit: Thanks for all your questions! We'll be picking up the most upvoted remaining Qs over the next few days. This AMA is part of a wider series of events and online activities taking place this week. Check them out -https://www.imperial.ac.uk/be-inspired/lates/

Our approach: Our approach to this vaccine is unique, both compared to other teams around the world fighting COVID-19, and to traditional vaccine development. Almost every viral vaccine ever developed involves injecting a small amount of a weakened version of the virus or viral protein into your body. But ours works differently. We are using RNA, the genetic material that encodes the surface “spike” proteins of the coronavirus, and injecting that into people. In this way, we are able to use your body’s cells as a bioreactor to produce the viral protein and hopefully trigger immunity.

The aim of our vaccine is the same as any other - to prep the body's immune system by getting it to create antibodies that will quickly destroy the virus if you become infected. However, there is nothing of the virus inside those spike proteins. Instead they are tricking your immune system into thinking it’s seeing the whole virus to elicit an immune response. The advantage of our vaccine is that we only need a tiny dose: 2 million doses can come from a single litre of vaccine as opposed to the 10,000 litres of vaccine that would be required by traditional methods.

Pushing forward: Results from initial trials in mice were positive. Antibody levels in the blood of vaccinated mice were higher than those measured in samples of recovered patients leaving a hospital in London. So we are now pushing forward in two ways. Firstly, through human trials to compare placebo groups with vaccinated groups to look for evidence of successful immune responses. Secondly, due to the severity of the global pandemic, we have had to assume success and start plans for mass distribution that will allow us to vaccinate a significant proportion of the world.

We’re taking a unique approach to this too. Rather than partnering with the pharmaceutical industry, we've launched a social enterprise, VacEquity Global Health (VGH) to bring our COVID-19 vaccine to the world. For the UK and low-income countries abroad, VGH will waive royalties and, due to the potency of the vaccine and this business model, we’re hoping to keep the price below £10 per dose. This modest cost-plus price will be used to sustain the enterprise’s work, accelerate global distribution and support new research.

During this AMA we would love to discuss what it’s like to work on a vaccine the world is waiting for, how we are ensuring the vaccine is effective but also safe, and the role of vaccines within society beyond COVID-19. 

Proof: https://twitter.com/AnnaBlakney/status/1310592457780981761

Useful links:

Comments: 927 • Responses: 35  • Date: 

MessfullStressfull617 karma

Since you've only carried out on mice, these 3 questions refer to your results of those experiments.

How long do the antibodies persist in the system after the injection? I've heard one of the biggest issues with some of the vaccines is the amount of time that a single injection provides protection.

Did all of the mice that received the injection achieve a level of antibodies that would at the very least, lessen the severity of disease (maybe decrease chance of lasting heart/lung damage) caused by COVID-19?

My third question is unlikely to have an answer within a mouse population, so I'm more asking for your hypothesis as educated researchers; do you feel that we have the potential to build herd immunity if "enough" of us receive the vaccine?

Thanks for taking the time to answer questions!!

ImperialCollege562 karma

From Anna: Thanks for your thoughtful questions! We are still in the process of observing how long the antibodies persist in humans - we actually can’t answer this question directly in mice. Humans and mice have different immune systems and respond differently to the same vaccine, so this is one of the main things we’re looking at in our clinical trial. Obviously it’s more ideal for the vaccine-induced antibodies to last a long time so that people don’t need to be vaccinated as frequently, which is what we’re striving for.

In our preclinical studies, even the mice that received a dose of 0.01 µg (10 ng, tiny dose!) had antibody titers (a measurement of how much antibody an organism has produced) that were higher than patients at our local hospital that had recovered from COVID-19. At this point, it’s hard to know exactly what antibody levels are required to prevent infection or lessen the severity of the diseases (called the ‘correlate of protection’), so all we can do in the meantime is compare it to a natural infection. As vaccine candidates progress through clinical trials, we’ll have a better idea of what these levels are.

If everyone on the planet were to receive a 100% effective COVID vaccine with long-lasting immunity tomorrow, we would of course have herd immunity! I do think we’ll get there eventually, but it depends on a number of different factors: how long the immunity lasts, how accessible the vaccines are (cost and availability), if the virus mutates, how quickly we’re able to scale-up production once a vaccine is licensed, etc. We’re passionate about making our vaccine accessible to as many people as possible, especially in low- and middle-income countries that may not have vaccine programs of their own, which was our reason for starting VacEquity.

UnicornHostels340 karma

How much would the virus need to mutate for a vaccine to be ineffective? How likely is it to mutate into a new strain, like influenza, to make a vaccine ineffective?

ImperialCollege477 karma

From Anna: As you can imagine, mutations are constantly being monitored globally. Relative to influenza, SARS-CoV-2 is mutating much less quickly, which is quite a relief. As for how much it would need to mutate to render a vaccine ineffective, it’s hard to say! Our vaccine, like other candidates in development, targets only a certain protein on the surface of SARS-CoV-2 called the ‘spike protein’, so this is the most concerning area for mutations. So far, there’s been one notable variation called the ‘D614G’ mutation in the spike protein, which is found globally. There is ongoing research to determine how this changes the conformation of the protein and the efficacy of the current iterations of the vaccine. One major advantage of our vaccine platform is that it’s quick to make a new version, so if there was a disruptive mutation and we needed to make an entirely new vaccine with a different RNA sequence, we’d be able to pivot to address this.

tantothemighty323 karma

How long will it be, in your personal estimations, before a widely available and safe vaccine is on the market?

ImperialCollege463 karma

From Paul: We don’t know for sure but hope to have an effective vaccine sometime during 2021 - which is still really soon compared to a standard vaccine development program. The issue of wide availability is more tricky! Hopefully if a low cost and safe vaccine becomes available then it can be supplied globally and is affordable for low-middle income countries.

YouMightGetIdeas108 karma

I'm completely obtuse when it comes to medicine. Is there such a thing as doing a rush job when developing a vaccine or there's no way to cut corners?

ImperialCollege180 karma

From Paul: Like everythng in life it is easy to cut corners BUT it is so important to get this right and to be safe for many reasons. I can think of two straight off - that we really aren’t in the business of harming people and also we want to make a difference to the pandemic and perhaps prevent people from becoming exposed and infected. We have spent a lot of time making sure our vaccine candidate is safe and this will be a continuous process throughout each stage of the human clinical trials.

evil_666_live165 karma

So everyone is saying mRNA vaccine has never been proven before by market, what's your thought on that?

Can you be more specific about how your RNA product different with those from Moderna and BioNTech? I can read and interpret technical terms, please share what you can.

ImperialCollege198 karma

From Anna: Great question! There’s currently no clinically approved mRNA vaccine or therapy, so it’s true that they’re unproven as of yet. One of the positive aspects of the SARS-CoV-2 pandemic is that it’s been kind of an ‘RNA renaissance’ wherein a lot of these technologies have been tested for the first time and there’s been a lot of education for the public about what RNA is and how it works.

Each organization uses a slightly different type of RNA. Moderna and BioNTech both use mRNA; Moderna uses modified nucleotides (one of the RNA bases [A, U, G, C] is slightly different than the one found in nature) whereas BioNTech uses the natural bases. Ours is also a type of mRNA, called self-amplifying RNA, that encodes four extra proteins that work as a replication machine to make many copies of the original strand of RNA. This allows us to use a much lower dose, and like BioNTech, we use the natural RNA bases.

SoCalTiger1347 karma

Is there a potential risk in using a self-replicating vaccine? Specifically, is there a risk that there could be "runaway" replication? What would that look like and what would the result be?

Alternatively, could this be a benefit if it managed to replicate at low levels for a long time? Not sure if this is even a possibility but would this provide a longer term of protection if it happened?

ImperialCollege6 karma

From Anna: Great question and I’m sure a concern for many! It’s highly unlikely that we’ll have ‘runaway’ replication. Our bodies have evolved over time to efficiently detect foreign RNA (as this is how a lot of viruses attack cells) so while the saRNA gives slightly longer expression than mRNA, it still gets shut down eventually. Even if it did replicate infinitely, it just means that it would continuously produce the encoded protein as opposed to turning back into a replicating virus or something. We’re still doing studies to understand the benefits of low replication for a long time versus short bursts of replication, but they likely have different effects on the immune response.

Nihhrt127 karma

Let me say first that I appreciate your work as many others surely do, but I'll ask a negative question.

With your type of vaccine, what's the worst that could happen if it doesn't go right?

ImperialCollege91 karma

From Paul: Thanks for your appreciation! As with any medical intervention or vaccine there are risks, and our vaccine is no different. We do a lot of studies (safety, immunogenicity, toxicology) to minimise these risks prior to human clinical trials, and even though we have made this vaccine really quickly we have done everything possible to make sure it is safe.

ImperialCollege178 karma

From Anna: Furthermore, the type of vaccine we use (based on RNA) is a relatively safe vaccine, as it is made synthetically, so we’re not introducing a live or attenuated virus into the body. RNA vaccines are a new technology, so really for us the bigger ‘risk’ is if the vaccine just doesn’t work in humans at all.

hobnobbinbobthegob11 karma

This is essentially a non-answer. Literal millions of people are wary of corona virus vaccination based on fears of potential side effects. Some of these people are anti-vax-indoctrinated lost-causes, but many are just going to need to hear that the "worst case scenario" is either mild or extremely unlikely.

To answer "What could happen to me if I get this vaccine" with "This isn't a new technology" or "We have done everything possible to make sure it's safe" is insufficient.

ImperialCollege167 karma

From Anna: I hear your frustration! We do the clinical trials to answer these questions, and it’s impossible to speculate on the likelihood of ‘worst case scenario’ before they’re complete. And since we’re scientists, we’re not in the business of speculation. At the end of the clinical trial we will have tested the vaccine in thousands of people and will publish our results, including exactly how many, if any, ‘adverse events’ happened during the trial. This data is then what determines whether the vaccine is safe and effective enough to license for public use.

UraniumGeranium12 karma

I definitely see where you are coming from, and happy that you aren't throwing wild speculations out there that could be misinterpreted as things that could actually happen. Many people will still be worried about "worst case scenarios" though, maybe one way to help quell those fears is to rule out possibilities that definitely won't happen.

I'm not a biologist, so it's easy to imagine some scenarios that sound plausible but are likely refuted by science. I'll list a few that come to mind. If you or anyone else can explain why these are nonsense, that would be great!

  1. You're using a version RNA that can self replicate in a cell. Can this replication get out of control, similar to cancer?
  2. Normally specific immune cells develop the antibodies (is this correct?). If this RNA you are injecting can enter any cell to make the antibodies, could it disrupt that cell's normal function by taking resources away?
  3. The immune system is designed to fight infections, could the effects of this replicating RNA be seen by the body as an infection, and the immune system could produce antibodies to kill the RNA rather than the spike proteins they are making? Could this somehow backfire and make you more susceptible to covid because the immune system is fighting the thing that generates protection from covid?

Again, not a biologist, so I don't know what I'm talking about and nobody should believe these speculations. Still very interested to know why these kind of scenarios wouldn't happen from someone who does know what they are talking about.

ImperialCollege3 karma

From Anna: Thanks for the well-thought out and specific questions! See answers below:

  1. I’m sure the replication aspect is concerning for many when you first hear about it. It's highly unlikely that the replication will get out of control. Our bodies have evolved over time to efficiently detect foreign RNA (as this is how a lot of viruses attack cells) so while the saRNA gives slightly longer expression than mRNA, it still gets shut down eventually (within 30 days in mice). Increasing the time that the RNA exists in the cells is the perpetual uphill battle of the field of RNA delivery. Even if it did replicate infinitely, it just means that it would continuously produce the encoded protein as opposed to turning back into a replicating virus or something.
  2. You’re correct that normally specific immune cells develop the antibodies (called B cells). Our RNA actually doesn’t encode the antibodies directly, just a protein from the surface of the virus, called spike. Thus, the mechanisms of immune response are similar to a normal vaccine: once your cells make the spike protein other cells take it up, chop it up and then tell B cells to make antibodies against it. However, you’re correct in that we are hijacking the cellular function to make our protein, in addition to the normal proteins. Luckily, cells are quite efficient at pumping out proteins, so they are able to cope with the extra burden. From what we’ve seen, the RNA gets into relatively few cells (again, we’re highly evolved to resist foreign RNA) so only a small subset of your cells are impacted and there’s not a systemic effect.
  3. As I mentioned above, the RNA is detected as foreign. This actually works as an advantage for RNA vaccines though- because your body has detected a foreign RNA, it enters an antiviral state, and then when it makes the spike protein this is what helps stimulate an immune response to it. If you got a massive dose of RNA and enough cells in your body were in this antiviral state it could weaken your immune response to a pathogen, but we use relatively low doses of RNA (0.1-10 µg in our trial) so this isn’t nearly enough to observe systemic effects against the RNA.

Hope this helps, and happy to continue the conversation if you have any follow-up questions!

_FAPPLE_JACKS_98 karma

Would you rather fight 1 covid infected horse size duck or a 100 covid infected duck size horses?

ImperialCollege66 karma

From Paul: Duck sized horses for sure.

ImperialCollege51 karma

From Paul: I’m torn on this one. I really want to see 100 tiny horses. But 1 big duck would also be fun to see and maybe easier to treat?

My_Username8276 karma

How much pressure do you guys feel to get this right? How much does that effect your personal lives and mental health?

ImperialCollege147 karma

From Anna: I think Paul would agree that while there is a lot of pressure to deliver on this vaccine, we’re more excited than stressed to be able to work on this project. As a scientist, one of the main motivations is that my work could one day have a positive impact on human health- very few researchers actually have the opportunity to do this. There have definitely been challenging times for my mental health during COVID-19 as I’m quite a regimented person; I confronted this by establishing a new routine to stay balanced (doing yoga at home instead of going to a class, going on socially distanced walks, going for a run instead of going to the gym, cooking more often). That being said- I actually had it easier than most because I was still going into work so I didn’t have to confront the nightmare of working from home.

seunosewa68 karma

How likely is it for this vaccine to cause the immune system to attack the muscle cells replicating the vaccine RNA and pumping out the spike protein?

ImperialCollege97 karma

From Paul: Thanks for your question! The whole idea of a vaccine is to cause the immune system to attack the virus or cells that are expressing parts of the virus. In a natural infection, the cells infected with a virus are deliberately killed and removed by the macrophage and dendritic cells of the immune system. When we inject the vaccine a small number of muscle cells will express the coronavirus spike protein but most of the immune response will take place in the draining lymph node near to the injected muscle. This is a specialised compartment with the sole purpose of allowing the immune response to develop and mature and to make great antibodies and T cells against the virus. This is naturally what it’s meant to do and so the body is very capable of responding to the virus while protecting its own cells and structures - like the muscles!

EddyMerkxs47 karma

Should we be more skeptical of rushed COVID vaccines, or should we expect similar safety as traditional vaccine development?

ImperialCollege104 karma

From Paul: For sure, it does all seem rushed but not to us. We have been working on the platform technologies for our RNA vaccine for a number of years and when we saw the opportunity to contribute to the COVID vaccine effort we were sure we could help.

Also - even though we were able to make this vaccine in a very short time we have done all of the safety analyses that would be expected for any vaccine. This has actually been the slow part of our development but of course super essential.

Another thing to remember is that the clinical trials themselves are a continuous assessment and re-assessment of the safety of vaccines.

Hawk_The_Slayer45 karma

What percentage might not be protected and could you help us understand why this will be the case?

ImperialCollege57 karma

From Paul: At the moment we just don’t know how many people may not benefit from the vaccine and it’s likely that each vaccine will have slightly different percentages. This is one of the important questions asked during the efficacy stage of a human clinical trial (Phase III - the final stage) and we hope, for our vaccine at least, that most people will respond, make antibodies and be protected. There may also be differences in responses in the different age groups - older people may not respond as well as younger people and the Phase III efficacy trial will look at this issue too.

iJackyLegz39 karma

What company do you work for?

ImperialCollege134 karma

From Paul: We work in academia. Our funding comes from charities and government funding and so we don’t have any obligations to a company. We are interested in the research and in making the best and safest vaccine that we possibly can.

Twrd432135 karma

As vaccine researchers, how do you feel vaccine development is being covered by the media at large?

ImperialCollege81 karma

From Anna: I think it’s great how many people now know what an RNA vaccine is now! I often observe that the media tries to frame it as a race, but that’s not how it really feels within the scientific community. We work closely with other groups developing vaccines, e.g. we’ve completed preclinical studies looking at combining our vaccine with the Oxford/AstraZeneca vaccine for a prime/boost regimen. To me, it’s a good thing there are so many options in development, as nobody is prepared to make billions of vaccines in such a short time frame, so the more candidates the better.

PenguinsFalling32 karma

🦈🦈🦈🦈🦈🦈

Theres been news on the need for shark oil for the production of vaccines. It is reported/predicted that almost half a million sharks will be need to mass produce vaccines for this pandamic. How important is skark oil in the production? What components does it have which it so special/unique for vaccine development? Are there alternatives to this?

Ps: Thank you and your team for the work that you do. It is really inspiring! Esp for someone who looks to a future in virology!

ImperialCollege108 karma

From Anna: I think what you’re referring to is the use of squalene oil in nanoemulsions that have been used by some groups to deliver RNA. Historically this was derived from sharks, but it’s now possible to produce it from plants. We use a different delivery approach called ‘lipid nanoparticles’, which are basically just fat blobs that protect the RNA and help it get taken up into cells. Some of the lipids are engineered, and some of them are natural, like cholesterol, but all of them are shark-friendly.

Our pleasure, it’s definitely a fascinating field to go into!

steakonmynips26 karma

Thank you for all of the work you are doing!

Goes without saying, a lot of us are waiting in anticipation for the vaccine to be released. What are researchers doing to expedite the normal 5-7 year process and ensure an earlier release without compromising safety and quality?

ImperialCollege47 karma

From Anna: I think this is a common misconception that is often misrepresented in the media, so thanks for this question! Our RNA vaccine is really a platform- we can use it for any type of vaccine as long as we know what the protein is that we need to encode. We’ve been working on the platform for 4 years now. So while we pivoted our work to focus on SARS-CoV-2 in late January, we’ve actually been developing aspects of the vaccine for years now. We’re not able to compromise on the safety or quality of the production or trials of the vaccine, even in a pandemic.

liliaimerouge10121 karma

1) What are some of the challenges that come from using RNA instead of DNA?

2) what are the subject eligibility criteria for these trials? Do you have problems with getting the number of patients you need?

3) how do you get funding without a pharmaceutical sponsor?

I work on cancer drug trials so I'm very curious to see how your approach goes! Thank you for your very hard work!

ImperialCollege42 karma

From Paul: Great questions! RNA is much more tricky to work with than DNA, there are RNAses LITERALLY everywhere! But if you are careful and make sure everything is RNAse free then working with RNA is pretty much the same as DNA. Our specific challenge was that we were working with a super long piece of RNA, the replicon is 11,500 base pairs, which is enormous. And one nick in a single stranded molecule makes it useless.

The eligibility for Imperials trial is here - https://www.imperial.ac.uk/covid-19-vaccine-trial/participants-info/

Please do sign up!

We have historically been a well funded lab and we are funded mainly by charities and also by the government. It was interesting when we told the world that we had developed this vaccine and when we were in the process of publishing the paper a referee asked why we hadn’t partnered with a major pharmaceutical company yet. We haven’t and I think we’re doing pretty well!

William_Harzia21 karma

Based on how old age is by far and away the biggest risk factor for death from COVID, immunosenescence should be a particular concern for vaccine development.

Do you think your vaccine will stimulate a robust enough immune response in the elderly to protect them directly, or are you thinking more along the lines of protecting the elderly indirectly via herd immunity?

ImperialCollege38 karma

From Anna: This is something we’re looking into, and is always a concern for vaccinating the elderly. It’s fascinating but relatively not well-understood why we don’t respond to vaccines as well as we age- have we seen too many viruses? Does our body just get tired and shunt energy away from the immune system? We hope that our vaccine induces an immune response in the elderly, but no matter what, widespread vaccination and induction of herd immunity is the best way to prevent people of all ages from getting infected.

ruggpea20 karma

Hiii! Thanks for doing this! Sorry if these have been asked already:

  1. Corona viruses in general have been tricky to vaccinate against, why is this so?

  2. Reinfection with corona viruses is very common, will the vaccine you guys are working on stop any reinfections? (Could you explain why/why not if possible)

  3. Assuming a vaccine works, what is the timeline for the world to be protected and for corona virus to be either eradicated or no longer a threat? (I’m guessing a large number of the population will need to be vaccinated at the same time).

Thank you for your time!

ImperialCollege6 karma

From Anna: Great questions! See answers below:

  1. There was a lot of work done on MERS and SARS after those outbreaks (a lot of this research has accelerated and helped the fight against SARS-CoV-2) but eventually the efforts lost steam due to lack of funding. This is the main reason we don’t have vaccines for other coronaviruses yet.
  2. You’re correct that reinfections with coronaviruses is common, this is due to a short-lived antibody response. Studies have shown that the antibodies usually circulate for 3-6 months after a natural infection. The goal for the vaccine is to induce a long-lasting antibody response that prevents infections, without ever being infected in the first place. This way we avoid any complications from being infected with the virus.
  3. It’s really hard to say at this point! Assuming a vaccine, or more likely a few vaccines, ends up working then it depends on how quickly it can be produced, where it’s distributed, and how long the protection lasts for before you need to be vaccinated again. One of the advantages of our RNA platform is that it requires a low dose, so you can make 100X the number of doses in the same volume as normal RNA, which would obviously make the scale-up much easier!

Sometimesahippie18 karma

I am currently pregnant, Will this be safe for pregnant women as well? When I birth my baby, will it be safe for newborns?

ImperialCollege41 karma

From Paul: Congratulations! The clinical trials will eventually look at the safety and efficacy of the vaccine in many different situations, and this will eventually include pregnant people. However, here it is doubly important to make sure the vaccine doesn’t have any effect on the developing baby. I personally wouldn’t expect the vaccine to have an effect and I don’t think it would cross the placental barrier but of course this has to be closely studied.

The second part of your question is also answered, I’m afraid, with we don’t know yet. Newborns typically respond less well to vaccines than children over the age of 18 - 24 months but they do get vaccinated to a number of critical disease which are a significant threat to very young children and the question, apart from whether the vaccine works well in newborns, would also be whether the newborns are particularly threatened by COVID. I think this could mean that it may or may not be recommended by the government but that it would be a personal choice of the parent.

SEBrecords18 karma

Thank you for your hard work. I’m sure you all have become eye rolling experts in a lot of conversations on this topic!

My question: how are you addressing long term risks for potential reproductive side effects? My fiancée is a nurse, who will likely have mandatory vaccination. This this a non-issue or a calculated risk?

Keep on being badasses.

ImperialCollege27 karma

From Paul: Haha! I like the idea of being a badass though that is likely very far from the truth! We aren’t at all eye-rollers - we are super passionate about our work and love doing public engagement so that we can share the little we know. We are indeed looking into the potential for the vaccine to migrate to the testes and ovaries and this is something that would be constantly monitored. It is very unlikely that the RNA would appear in the reproductive organs but even if it did it can’t become incorporated into the DNA of the egg or the sperm. RNA can’t be reverse transcribed into DNA and so can’t be transferred to the next generation.

SodaCooler17 karma

How difficult was it to create this vaccine?

ImperialCollege36 karma

From Anna: The advantage of using the RNA platform is that it’s actually quite easy to create a new vaccine if a novel target arises - we were able to go from development in January to human clinical trials in June. That being said, we’ve been working on the platform for years now so we’ve definitely had our challenges and failures along the way to get to a point where we have a viable platform.

Karanpmc13 karma

What is the predicted efficacy based on data you have so far?

Separate question, what are the storage conditions for your candidate?

ImperialCollege43 karma

From Paul: Thanks for your questions! We are currently doing the Phase I and II clinical trials, these look at safety and immunogenicity - whether there are bad adverse effects and also critically whether the vaccine candidate makes a good response. The next stage, which we haven’t reached, will tell us how ‘good’ the vaccine is, the efficacy. Some other vaccine candidates have already started this phase of testing but they also wouldn’t have a clear answer for you. Your second question is really important too - we are looking into how to be able to store our vaccine at room temperature - which is the holy grail for vaccines. However, currently we need to keep our vaccine at -80 degrees.

TimeVendor11 karma

Can mRNA vaccine alter the dna of a human?

ImperialCollege11 karma

From Paul: Thankfully no! This is actually one of the major advantages of our vaccine (and also the other RNA vaccine candidates). RNA vaccines can’t be reverse transcribed into DNA and so there is no possibility that they can be accidentally inserted into our human genome.

belaveri19918 karma

Regular person here trying to help, we’ve been told that protein folding/folding at home is helpful for vaccine development. Do you utilize this type of data? If so why is it helpful?

ImperialCollege3 karma

From Anna: I think you’re referring to Foldit- which is a way of gamifying all the possible ways a protein can fold. This is a really cool way of utilizing the computing power of people at home to solve complex biological questions. Few are aware that RNA has a lot of secondary structure which is really important for its function, but as it’s a relatively new field the version for RNA does not exist yet. We would still benefit from the outcomes of Foldit as it increases our understanding of proteins overall and can help us design better antigens to put into our RNA.

justscottaustin6 karma

I've always wondered. How does one control this in human trials for the placebo? Give the placebo group the placebo then stick them in a quarantine ward with a bunch of Covies? Sorry suckers?!?!

Seriously. Seems a bit risky to the placebo group...

Can you explain like those of us on here have no idea? Because...well...

ImperialCollege23 karma

From Paul: Taking part in a human clinical trial is a fantastically generous and altruistic act and we are always extremely grateful that people will give us the opportunity to test our vaccine candidates on them. So we take it very seriously as you would imagine. Part of being in a placebo-controlled trial is that the participants fully understand that they may not receive the vaccine but that they will instead receive a placebo and they will not be protected from the virus. However, we don’t deliberately expose them to the virus, we monitor them and see if the number of people who have been vaccinated have fewer COVID cases than the people who had received the placebo. That’s how we can tell whether the vaccine is working, the difference in the numbers of virus infections between the control (placebo) and the vaccinated groups. This is the reason why this stage of the clinical trial needs so many people - many thousands are needed to clearly show if the vaccine is making a difference. And of course - this also needs the COVID virus to be circulating in the general population, if there are no infections in either group then obviously we can’t tell the difference.

columbo2226 karma

Has an RNA vaccine ever been used for other existing viruses in the past? Why try a novel vaccine method with a novel virus? Is it just coincidental timing (i.e. the technology wasn't available until very recently?)

ImperialCollege9 karma

From Anna: It’s a relatively new technology, so while there have been RNA vaccines for a number of different existing viruses (HIV-1, rabies, influenza, Ebola, Marburg to name a few) tested in animal studies and a small number of human studies, none of them are licensed for widespread use (yet!). The main advantage is that RNA is relatively cheap, rapid and requires a much smaller manufacturing footprint than other types of vaccines, which is why they’re useful for deploying in a pandemic.

thesploo3 karma

Let's talk storage and stability! What type of cold chain and shelf life is anticipated for your vaccine? All the different technologies have requirements ranging from -80C storage to room temperature stability. Once we get a vaccine that is worth using on the general population, distribution becomes the next major issue. Especially for rural areas or less-developed countries, room temperature stability will be critical.

ImperialCollege3 karma

From Anna: This is currently one of the most challenging aspects of the field! Our current protocol is storage at -80C, which as you said is impractical in many scenarios. We’re now working to define how long it’s stable once it’s thawed and stored at room temperature or in the refrigerator, and optimizing different storage buffers to prolong this stability.

Justakiss153 karma

Did you notice any side effects in the mice that received this vaccine? And has this type of vaccine been used in the past?

ImperialCollege13 karma

From Paul:

Thanks for your question! We saw no side effects in the mice when we tested the vaccine. We also did a toxicology study in rats performed by a commercial research organisation as this is required by the government for initial safety checks on anything that will go into humans. This toxicology study looks at all the organs and the blood cells in the animals to see if the vaccine had any pathology and nothing was observed. The vaccine was considered by this contract research organisation to be very well tolerated with no damage or pathology noted in any animal.

This type of vaccine hasn’t yet been used in a clinical product - there are no vaccines which use self-amplifying RNA or mRNA. So this is an entirely new vaccine type. We and others have however been working on the technology underpinning these RNA vaccines for many years. This is one of the reasons we are so excited about these vaccines as they can be made entirely synthetically and are really quite simple with few components that we believe will make them well tolerated and safe to use.

ReliableSource1 karma

I've always thought of the term "herd immunity" in terms of vaccines. With covid, I've seen a lot of people use the term irrespective of vaccines, as though if enough people catch it, herd immunity will just happen naturally.

What would you say to the people who talk about herd immunity through not wearing masks and allowing the virus to just run rampant?

ImperialCollege5 karma

From Anna: We can generate herd immunity through both natural infections and vaccines as long as they induce an immune response, typically antibodies. For SARS-CoV-2, like most viruses, it will likely be a combination. The problem with allowing the virus to run rampant is that the immunity may not be long-lasting (for other coronaviruses the antibodies usually stick around for 3-6 months) so the population may never get to a level where everyone has a protective amount of antibodies, and instead everyone is just repeatedly getting sick. In addition, we know very little about the short- and long-term effects of this virus since it’s brand new, so we’d prefer to have a way to prevent people from getting infected in the first place, hence a vaccine!