In an effort to make science and healthcare information accessible, Carbon Health has partnered with Rob Swanda, PhD to answer questions about Bivalent vaccines and boosters, from actual people (via Dr. Swanda’s Twitter followers). Dr. Swanda is joined by Dr. Aaron Weinberg, the national director of clinical research at Carbon Health, to tackle the COVID and bivalent vaccine related questions below, and many more in the full-length video discussion found near the bottom of this post.
Conversation Timing Note: This convo occurred prior to the FDA & CDC granting emergency use authorization for Moderna & Pfizer bivalent covid-19 boosters.
Dr. Swanda: “Have we seen this type of technology before, and if so for what other vaccines as some examples?”
Dr. Weinberg: “Yeah that's a great question Dr. Swanda! We have, this isn't a new thing to combine multiple forms of a vaccine together. We know that with all these viruses they mutate, they change, and it's important that we adapt our vaccines so we can train our immune system to respond to the different variants that emerge. So we do this all the time. We've done it with the HPV vaccine, which you may have heard of which helps prevent the virus HPV and also cervical cancer. We've done it with the pneumococcal vaccines where we combine multiple serotypes, or variants, into one vaccine. And pneumococcal bacteria causes pneumonia, it's one of the common causes of bacterial pneumonia in the country so we do that with that. And then just a common example is the annual flu vaccine. A lot of times they're quadrivalent meaning we combine four different types into the vaccine; two of them are for influenza A, one type of the flu virus and H1N1 as well as H3N2 are the serotypes, and then we also put in two influenza B forms of the virus as well. And that gives us broad enough immunity to protect ourselves against severe infection and death.”
Dr. Swanda: “That's great that we've been using this technology for a long time and now we're really just trying to take what has worked in the past and use it for a new virus that is mutating: Covid-19 or SARS-CoV-2, and really making sure that we have the best tools available in order to combat some of these infections.”
Dr. Weinberg: “Usually one thing to point out, I always like analogies, and one thing I like to think about is let's assume you had four different doors around your house with different locks. So you have your garage door, you have your front door, maybe you have a back door, they all have different locks. Let's say you need different keys in order to get into your house right? So what these multiple combined vaccines do is that they essentially tell your immune system okay these are the four keys you need to develop and then you can get into any of these doors and access your house. So that's kind of how I think about it.”
Dr. Swanda: “Some questions that individuals had were with these different strands of mRNA. One will be targeting the ancestral strain and one will be targeting the omicron variant strain, but are they protective against other strains that we've seen and potentially other strains that will still mutate in the future?”
Dr. Weinberg: “Yeah it's a good question! You're right this is the first updated vaccine we've seen since the initial one which was back in 2020, so it's about time. To be honest with you we needed to update our vaccines given the different variants that have emerged since, and the reason being is that the spike protein which is on the outer surface of the virus is really used to enter our cells and infect our body and infect our organs and lungs, and that has changed. There's been modifications to that and especially with omicron there's been significant changes to that spike protein to the point where our immune system doesn't recognize it quite as well and that's led to some of the infectivity that we've seen during this latest spike. So it's important that we update our vaccines to train our immune system to recognize some of these newer variants. Now with that said the old vaccines still protect you to a degree and we know that based on our data. If you look back to January 2021 we had about 10 deaths per million people in the US. Then when omicron emerged in February 2022 it was about greater than 7 deaths per million. And now we're down to less than 2 deaths per million and a lot of that has to do with the effectiveness of vaccines, antiviral therapies on the market, and then those that have been infected developing immunity. So our immune system is pretty good even with those initial vaccines at still targeting enough of the spike protein to clear it, however we definitely need to train our immune system to kind of get the newest version of Windows operating system in order to run efficiently. And the new vaccine is going to have the initial strain in it, so it's going to target the initial strain and then the update is going to be the BA.5 version, so that's really the part of the spike protein that it's going to target. With that said we've had BA.4 emerge recently, with BA.2 and BA.5 and both of those are very similar. So we really only need to create a subtype of the vaccine that targets BA.5 because that should also work against BA.4. And, BA.5 is one of the highest circulating forms of the virus right now, so over 90% of the cases are due to BA.5, which is really why they're using that and combining that.”
Dr. Swanda: “When individuals are hearing about these boosters potentially becoming available, at least in the US in the short term, there's been a lot of talk about when someone should go get a booster, and if they recently got their third shot or maybe if they were over 50 or 65 and they got that fourth dose when should they be moving forward to try and get this bivalent vaccine booster to increase their protection? Do you have a (timing) for that?”
Dr. Weinberg: “Yeah, again I think just to kind of take a step back everyone five years and older should get one booster after completing the primary series, so we're kind of at a point now based on the data that we've seen that it really is worthwhile to get if you're five and older, to get at least one booster. Now if you are 50 years and older then the recommendation is to get two boosters. In addition to that if you're 12 years and older and you have an immunocompromised state meaning your immune system is impacted, whether it's due to being on certain immunosuppressive medications or having an underlying condition that lowers your immune system response, those patients we're also recommending two boosters. With that said in terms of the timing, what we'll have to see when the FDA releases this exactly, what the window is gonna be between your last booster or your initial primary series and this one, but I would imagine it's probably gonna be on the order of anywhere from four to five months since your previous one that tends to be the period of time when your immunity tends to wane. We know with a lot of vaccines whether it's the flu vaccine or others over time our immunity tends to wane and then we need to have a booster in order to spike it back up. Now with the flu as opposed to Covid we tend to see an annual flu. Flu doesn't tend to happen constantly throughout the year, so that's why we only usually need to boost our immune system around that fall/winter time once a year. With Covid we've had to do it more frequently because we've seen these variants and these spikes in the pandemics. So I hope we get to a point where it becomes more seasonal and we're able to maybe spread it out a little bit further and do it annually.”
Dr. Swanda: “Yeah and I completely agree! I think that having it seasonal and maybe around the time of the flu is a great idea, and it also kind of falls in line with the way that society moves in terms of a lot of events take place in the fall and winter time that push people indoors and we know that that's where SARS-CoV-2 can spread a lot quicker, so I think that that's quite helpful. And, on a more innovative standpoint we have different types of vaccines that are coming out that may allow us to actually get one shot but have it for multiple viruses, like flu and Covid. So that's also something cool to be looking forward to in the pipeline.”
Dr. Weinberg: “There are some clinical trials about to start right now that are combining flu as well as Covid boosters, so you can kind of do it all in one!”
Dr. Swanda: “Yeah exactly, I mean the less shots that people have to get the better! And it's actually more protection, less needles.”
Dr. Weinberg: “But, going back to your point in terms of timing I get the question a lot of 'I'm due for a booster right now, but I hear that this one, this bivalent vaccine, is coming down the pipeline in the next month or so should I wait?' I would say that you have to take into account a few factors. One: you know what your risk status is? Are you very immunocompromised and vulnerable where if you do catch Covid in the next month will it lead to a worse outcome for you? Are you going to be doing significant travel in the next month? Maybe you're taking a big international trip or something that puts you at higher risk, so there's certain things that may factor into a decision. With that said if you're mostly careful and cautious and around the house and people that you trust then maybe waiting a few extra weeks for the newer vaccine may make sense in that case.”
Dr. Swanda: “Another concern that somebody had in our audience was 'what if there's not enough doses in the US?' But, I don't think that that's something we have to worry about from what I've read the US has already ordered more than 170 million doses, maybe even more since the last time I looked at the numbers, of both the Pfizer and Moderna bivalent vaccines, so I don't see there being too much of a bottleneck in terms of actually having enough doses available.”
Dr. Weinberg: “And the great thing about the mRNA technology is it's really easy and quick to produce more copies and more vaccines compared to our traditional models of developing vaccines where you had to grow them in eggs or other methods, so I think with that said we've seen with these boosters that we're not doing a great job with the population receiving them, so we probably have more supply than we do demand and we need to change that. We really do need to protect people against this virus still. I looked at the data of patients over 65 years old recently and 92% got their initial series, which is great, but then only 70% got their first booster and only 40% of those 65 and older got a second booster, so even though it's indicated for that age group we need to work on getting people boosted. And for those who haven't received an initial series maybe they're a little bit hesitant to receive an mRNA vaccine, even though we've had millions and millions of people receive them all around the world with very few side effects and very good safety data, but some people are concerned about that technology. And for those people I would say we have other vaccines on the market for an initial series such as the Novavax vaccine which is more of a traditional protein based vaccine, and I would encourage someone if that is their fear and concern to definitely consider getting the Novavax vaccine.”
Dr. Swanda: “And, something cool too with Novavax is that they are also applying to be used as a booster, so that's potentially coming soon and they're still working in their pipeline on having these variant specific protein based boosters, so they're in clinical trials now, but that's also something to have in the future where we'll have an array of different options for whatever somebody has a preference for.”
Dr. Swanda: “Looking a bit towards the future as we know that SARS-CoV-2 will continue to mutate, it mutates just because of those infections. Every time it has the chance to replicate, that's another opportunity for it to mutate. So there's questions on will there be updated bivalent vaccine boosters in the next year, two years, which kind of touches on what we talked about as an annual shot, and could we begin to see multiple, more than two strands or information of mRNA, input into some of these vaccines? What are your thoughts on that?”
Dr. Weinberg: “Yeah, again it's a little bit of guesswork at this point but I think that we're just gonna have to see what variants emerge and how dominant those variants are, and how different the variants are from previous variants. The more different they are, the more likely they'll evade our immunity that we've built up and we may have to modify the vaccine. But that's still to be seen and to be determined. I think you raised a great point: we really do have to cut down on spread somehow. We have to break this kind of year-long cycle that we're in because like you said every time you make a new copy of the virus and spread it there's a chance for that mutation to appear to occur and we just don't want to get to a point where we're developing more deadly versions of the virus or changing the virus to a degree that it completely evades our immune system. So, I think that's important. There's some work being done on nasal vaccines right now, and the idea being if you can vaccinate using a spray in the nose and there's precedent for this we've done this with other infections and viruses before then you develop something called mucosal immunity meaning the immunity starts right in the nares inside your nose where the virus enters your body and hopefully cuts down on its ability to even get inside of your body and cause infection, and therefore stop that cycle of spread. So, that's one theory that some individuals are working on but I think the quicker we can cut down on spread then hopefully we can kind of lengthen the time that these variants emerge and maybe we'll get to more of a seasonality sort of state, which is the ultimate goal. I don't think we're going to eliminate Covid altogether, I think it's going to be endemic and here to stay, but hopefully it can be more manageable and become more like the annual flu.”
Dr. Swanda: “We also know that you're involved in a lot of clinical research ongoing at Carbon Health, so could you give us just a little snapshot of some of the things that you might be working on that you can discuss with the general population?”
Dr. Weinberg: “Early on we were heavily involved in the Molnupiravir studies which were the Merck antiviral pills. We've been involved in some exciting diagnostic studies, and we have a few coming down the pipeline in that area. We've been involved in Covid vaccine studies. Very recently we were actually doing a combination vaccine study looking at pneumococcal vaccines combined with Covid boosters. We're going to be doing a couple more vaccine studies coming up here in different areas and we're about to launch a new exciting hypertension study for those that have high blood pressure using an RNA technology called interference RNA and we're really excited about that. I can't give too many details about it, but I'm really excited about the future and management of some of these chronic conditions with some of these new technologies which could be game changing.”
Check out the full conversation posted on August 29, 2022.
To see if Carbon Health offers COVID vaccines or boosters near you CLICK HERE.
Rob Swanda, PhD is an mRNA biochemist and science communicator who obtained his PhD from Cornell University in 2021. Follow Rob Swanda, PhD on Twitter: @ScientistSwanda
Dr. Aaron Weinberg is the director of clinical research at Carbon Health with a background in pulmonary critical care and internal medicine. Follow Dr. Aaron Weinberg on Twitter: @AaronWeinbergMD