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Hey guys, this is Pathogen Perspectives the podcast, where we will bridge the dangerous gap between the science of infectious diseases and public perception. So you, can keep it in perspective. I'm your host, Dr. Heather Lander.

Welcome back. Last week we talked about messenger RNA vaccines, and today we're going to take a look at the other vaccine platforms in development to protect us against COVID-19. Now, these vaccines in development all aim to do the same thing: to generate an effective immune response that will protect us from natural infection with the SARS2 virus and COVID-19 disease.

00:56 Self-Replicating mRNA Vaccines
Since we already talked about messenger RNA vaccines, I want to first talk about something called self-replicating messenger RNA vaccines. As the name suggests, self-replicating messenger RNA vaccines can replicate themselves, unlike the regular messenger RNA vaccines we talked about last week, which cannot. The advantage of a self-replicating messenger RNA vaccine is that it would require a much smaller dose than the Pfizer or Moderna vaccines. Now, don't let the idea of a self-replicating messenger RNA vaccines scare you. While the messenger RNAs in the vaccine can self-replicate, they are still targeted for degradation in the cells just like regular messenger RNA and they are also limited by the same natural laws as regular messenger RNA. They still cannot affect your DNA.

Okay, so self-replicating messenger RNA vaccines can either be delivered in the same way as regular messenger RNA vaccines, by being encased in a lipid bubble, or they can be incorporated into something called a viral replicon particle. A viral replicon particle is not a virus, it is a virus-like particle that carries the messenger RNA. And it cannot replicate. Only the self-replicating messenger RNA delivered by the particle can replicate.
The interesting thing about the viral replicon particle delivery system is that those particles cannot spread beyond the cell that they initially enter. This means the dose of the vaccine must be high enough to have enough replicons enter enough cells to generate a robust immune response. Currently, there are two vaccine candidates in phase II clinical trials that are using self-replicating mRNA platforms. It'll be really interesting to see how their data compare to what we have for the non-replicating messenger RNA vaccines that we have already authorized for emergency use.

02:55 DNA Vaccines
Okay, next on our list are DNA vaccines. DNA vaccines use what's called expression plasmids to carry the genetic code for the target protein. In the case of COVID-19, again, this is the spike protein of SARS2. Now compared to messenger RNA vaccines, DNA vaccines add an extra step. Instead of having messenger RNA that you then make the protein from, this vaccine starts with DNA. So our cells must transcribe the DNA into messenger RNA, then make the protein from the messenger RNA. This extra step also means that the scientists making these DNA vaccines have to build into the expression plasmid ways to ensure that that process happens accurately. 

Okay, so the benefits to DNA vaccines are that they are easy to mass produce, and they're very stable. This is why forensic scientists can collect DNA from crime scenes long after a crime was committed. And for vaccines, this means they are easy to transport and store. Another benefit to DNA vaccines is that they usually induce both a cellular and humoral immune response. The cellular immune response includes things like T cells and memory B cells, and the humoral immune response generates antibodies, despite the apparent benefits of DNA vaccines. Currently, there are no DNA vaccines approved for human use in the US, although there are several DNA vaccines approved for veterinary use in the US.

Right now, there are several DNA vaccine candidates in phase II clinical trials and there are two DNA vaccine candidates in phase III clinical trials. One of the companies with a DNA vaccine in a phase II clinical trial right now is called Inovio. And they are using a really interesting technique to deliver their DNA vaccine; they're using injection in the skin, followed by what's called electroporation. Electroporation uses electric pulses to get the DNA expression plasmid into your cells more efficiently. This is kind of fascinating to me, because I've used electroporation in the lab. It's not something I would have thought to use on myself, but it kind of makes sense. And I'm really curious to see what their data shows when the trials are over. Now, one setback Inovio already had with this delivery system, is that the FDA put their vaccine on hold on September 28, due to concerns over the electroporation device. And on November 16, they got permission to move forward. They are now running phase II trials in the US, China, and South Korea. If this one works, it'll be the only genetic vaccine - that is, one using DNA or RNA - that is stable at room temperature for more than a year. And that would be really beneficial in areas that require transportation to great distances in areas that lack a lot of refrigeration or freezer capacity.

06:17 Protein-based Vaccines
All right, so the next vaccine platform I'm going to talk about are protein-based vaccines. And these vaccines contain lab-generated Coronavirus proteins. These are not proteins that were removed from a virus particle. These are proteins that were generated in a lab from the genetic code. Protein-based vaccines can use either whole proteins like the spike protein, or they can use small pieces of a protein that we call peptides. Proteins and peptides generated in labs for vaccines are usually not very efficient at generating an immune response. So they require what's called an adjuvant in the vaccine formulation. An adjuvant is something that increases their ability to generate an effective immune response. And there are several adjuvants that we use in vaccines already, that have been proven to be safe and effective.

Currently, there are several protein-based vaccine candidates in phase III clinical trials. One of those, the EpiVacCorona vaccine, made by the Vector Institute of Russia, has also been authorized for early use in Russia. And it's the only protein-based vaccine that's been authorized for early use at this point. Now, there was one protein based vaccine that you may have heard about, that was actually abandoned, and is no longer in development. And this is the vaccine candidate from the University of Queensland in Australia. They were using the whole SARS2 spike protein in their vaccine. And it turns out that the spike protein, when not attached to a virus particle, can unfold. And if the protein unfolds, then it's not in the correct configuration to elicit an accurate immune response. So to prevent unfolding, the scientists working on this vaccine developed a tiny molecular clamp to keep the protein in the right shape. Now, the clamp turned out to be similar to an HIV protein, which led to generation of anti-HIV-like antibodies. So… antibodies that kind of look like antibodies against HIV. And the presence of these HIV-like antibodies led to trial participants testing positive for HIV antibodies. And that's the reason the trial was halted, and this vaccine candidate abandoned. So my question regarding this vaccine candidate and maybe they're looking at this, I don't know. But I'm curious if these HIV like antibodies could be effective against HIV? And if not, could they make that clamp look even more like an HIV protein? Could they generate a vaccine that worked against HIV and COVID-19? That would be really incredible as we don't have an effective vaccine against HIV. And there is one vaccine platform that I'm going to talk about later, that actually might increase the risk of HIV in certain individuals. 

Now, since this particular vaccine candidate brought up the issue of the unfolding of the spike protein when it's not attached to a virus particle, some of you might be wondering why then do mRNA vaccines work when they generate spike proteins that aren't attached to virus particles. And the reason those proteins don't unfold is because once the messenger RNA makes the proteins, they are inside the cell. And then they are moved to be displayed on the outside of the cell. And being displayed on the outside of our cells is a lot like being displayed on the outside of a virus particle. So the protein is in the right configuration and won't unfold.

10: 16 Attenuated and Inactivated SARS2 Vaccines
Okay, let's move on to talk about whole Coronavirus particle vaccines. The only way we can use an intact Coronavirus particle for a vaccine is if we use one that does not make us sick. We need one that will generate an immune response to the wild type deadly coronavirus, but won't make us sick. And to do that, we use inactivated or attenuated virus vaccines.

10:43 Attenuated Virus Vaccines
Attenuated virus vaccines are vaccines that use a live virus that has mutated so that it will not make us sick. And the word for that is attenuated and an attenuated virus won't make you sick. The process of attenuating a virus in a lab takes a lot of time, and requires what is called serial passaging of the virus in tissue culture, or in animals. This means that you grow virus in either a plate of cells or in an animal, and then you remove some of that virus and put it into a new plate of cells or a new animal. The first plate of cells or the first animal is considered the first passage of the virus. When you move it into a new animal or plate, it's called the second passage and so on. This repeated passaging of the virus forces it to replicate, and replication is where you get mutations. Then at each passage of the virus, you can check for mutations that may have caused attenuation. Now, attenuation can also be caused by genetically changing the virus yourself in ways you think will cause attenuation, and then checking to see if that's what happened. Currently, there is one attenuated virus vaccine candidate for COVID-19 in development, and the researchers working on this one used the second method. They are genetically engineering what they hope to be an attenuated SARS2 virus that will still elicit a robust immune response that will be effective against wild type SARS2.

12:28 Inactivated Virus Vaccines
Now, the other method of getting a whole virus particle vaccine using SARS2 that will not make us sick, but will elicit an immune response is by using what is called an inactivated virus vaccine. Inactivated viruses are also called killed viruses, and they can't make you sick. And unlike attenuated virus vaccines, killed or inactivated virus vaccines cannot replicate. Inactivated virus vaccines have been in use for over 100 years and are currently in use. In fact, the vaccines for polio, rabies, hepatitis A, tick-borne encephalitis, and most flu vaccines are inactivated virus vaccines. To make an inactivated virus vaccine, scientists must grow up a ton of live virus and then kill it in a way that renders it inactive. In other words, it won't be able to replicate, but leaves the virus particle intact to generate an immune response. Inactivated virus vaccines also usually require inclusion of an adjuvant in the formulation to increase the efficiency of the immune response generated.

The benefit of these inactivated or attenuated whole virus vaccines is that the immune response generated is to more than just one single virus protein. This means that it would take many virus mutations in those proteins to happen at the same time for the vaccine to be rendered ineffective, and that is highly unlikely to happen. This is a well-proven vaccine platform. And I wish more money had been invested in this approach early on. Currently there are four inactivated SARS2 vaccine candidates for COVID-19 that are in development and are currently authorized for early use in some countries. Three of them are out of China and one is out of India. The Chinese state owned company Sinopharm has two such vaccine candidates currently in phase III clinical trials. One was designed by the Beijing Institute of biological products, and it's called BBIBP-CorV and it has been approved for early use in China, the United Arab Emirates, Bahrain, and Egypt. And it looks like its efficacy is between 79 and 86%. The other vaccine candidate that Sinopharm has in phase III trials right now was developed at the Wuhan Institute of biological products, and it has been authorized for early use in China. You might remember hearing about this one. This is the one where in Peru the clinical trial was stopped because of neurological problems in one participant. The case was investigated and determined to not be caused by the vaccine. It's unclear at this point if Sinopharm is going to move forward with both of these vaccines. The third inactivated vaccine candidate for COVID-19 out of China is from a private Chinese company called Sinovac. This vaccine is in phase III clinical trials and has been authorized for limited use in China. And they have an agreement to supply Indonesia and Ukraine with doses when it's ready. The inactivated vaccine candidate coming out of India was designed by Bharat biotech in collaboration with the Indian Council of medical research and the National Institute of Neurology. It has been authorized for emergency use in India, despite having no phase III trial data yet.

15:59 Repurposed Vaccines
Okay, now I'm going to talk about something called repurposed vaccines, and it's kind of self-explanatory. These are vaccines already in use that may also turn out to protect against COVID-19. Currently, there's only one of these type of vaccines in a phase III trial, but we're likely to hear about more in the future. The Murdoch Children's Research Institute in Australia has a phase III trial going for a tuberculosis vaccine that was developed in the early 1900s, and is in fact still widely used today. Evidence indicates that this vaccine protects from more than tuberculosis, including reducing incidence of respiratory infections. It'll be interesting to see how this trial turns out.

16:51 Viral Vector Vaccines
Alright, it looks like we're onto the last category of vaccine platforms that I'm going to talk about. And these are viral vector vaccines. These vaccines use non SARS2 viruses to carry SARS2 genetic material, or proteins into our cells. Some viral vector vaccines carry the genetic material and our cells make the proteins. Other viral vector vaccines slowly replicate, and they display the target virus proteins on their virus particles. In either case, the virus vector elicits an immune response that's protective against the target virus. Viruses used as vectors in vaccines are genetically altered, so that they can't make us sick. In the case of vectors that don't replicate, they were also altered to remove the genes necessary for virus replication. Viruses that have been used as vectors in vaccines include measles, vesicular stomatitis virus, and Middle East respiratory syndrome-related coronavirus.

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17:53 Challenges to using Viral Vector Vaccines
So there are a couple of challenges using this vaccine approach. And the first one is that if you introduce a virus to carry the protein of the virus you're targeting, your body's gonna produce an immune response to both. Now what I mean by that is that your body will generate an immune response to the vector and to the target protein the vector is carrying. This usually means that if a second dose of the vaccine is required, it will be less effective than the first dose. This is because for the second dose, your body has seen the vector before. And so you will generate an immune response and clear the vector. And there is a good chance that this could happen to at least some degree, before the second dose has had a chance to initiate an additional immune response to the target protein on the vector. This just makes it harder to get a really strong immune response to the target protein.

Now the second challenge I mentioned is related to this idea that we will generate an immune response to the vector. So what if before the first dose, we already have immunity to the virus vector? This happens with viruses that are really common, especially adenoviruses. A good example of this are adenoviruses that cause the common cold, especially the one called Ad5. Most of us have been infected by Ad5 at some point in our life, probably more than once. And if we start off with immunity to this vector, then even the first dose of the vaccine will be less effective because of the immune response that we will have to the vector itself. This is why I was so disappointed early on when we found out that there were so many Ad5-based vector vaccines in development for COVID-19. We've never really been able to get one to work for humans. In fact, over the last three decades, more adenovirus vaccines have been administered to people in clinical trials, than have messenger RNA or DNA vaccines. And yet, we still do not have one licensed for use in humans. Currently, there is one adenovirus vector vaccine that is licensed in the United States and it is a rabies vaccine for use in wild animals. Now, there is another adenovirus vector vaccine that uses Ad5. It's made by a Chinese company called CanSino, which was founded by vaccine developers who had previously worked at Sanofi, those scientists developed an Ebola vaccine for the 2014 epidemic and in 2017, China approved it, but only for emergency use and stockpiling. And with a significant caveat. This caveat is that the phase II study data that they have for this vaccine did not demonstrate that it prevents Ebola.

Scientists who work on these vaccines, including the Ad5 vaccines, have been quoted in articles over this last year, saying that this approach is tried and true. But from everything I've seen with these vaccines, and the fact that we still don't have one, I don't really think that's an accurate description. And I think our money would be better spent pursuing other vaccine platforms that are actually tried and true, or that are showing much more promise. But I'm not in charge. So there you go.

Now, some scientists are probably trying to overcome this limitation, with Ad5 vaccines especially, by increasing the vaccine dose, in the hopes that an increased dose will generate enough of an immune response to the target protein, that the immune response to the vector itself won't be a problem. So my concern with this idea is that increasing the dose could also increase the risk of side effects. And usually side effects in vaccines are very minimal. As we've seen, it's very rare to have a genuine, serious adverse events with a vaccine. This is something we have data on, this is not new. And I have an entire series on the safety of vaccines, on my blog, with citations and everything. But I'm bringing it up now, because immunity to the vector itself is not the only concern with Ad5-based vaccines. And in fact, another concern with Ad5-based vaccines is HIV. Yep, I said HIV. Weird, right? I know. So let me explain.

22:39 Ad5 & HIV Acquisition
Two previous HIV vaccine trials called STEP and Phambili phase IIB studies, both used Ad5-based vaccines against HIV. And both showed an increase in the risk of HIV infection in men that were Ad5 seropositive, before they got the vaccine. In other words, in both of these trials, in men who had a history of Ad5 infection, taking the Ad5-based HIV vaccine actually increased their risk of HIV infection. And this was the same for heterosexual and homosexual men in these studies. This was a big deal, right? So, to address this issue, and decide on recommendations regarding the use of Ad5 as a viral vector for vaccines, the NIH sponsored what is called a consensus conference in 2013, about Ad5 vectors. Now, the leaders of the STEP and Phambili HIV studies published a letter in Lancet last October, October of 2020, in which they describe the data on Ad5 and HIV acquisition, and in which they clearly articulate their concerns with Ad5-vectored vaccines and the consensus conference warning to vaccine developers. And I'd like to go ahead and quote a couple of sections from that letter. The first is “that non HIV vaccine trials that use similar vectors in areas of high HIV prevalence could lead to an increased risk of HIV acquisition in the vaccinated population in men.” They go on to say that, and I quote, “This important safety consideration should be thoroughly evaluated before further development of Ad5 vaccines for SARS-CoV-2, and informed consent documents of these potential risks should reflect the considerable literature on HIV acquisition with Ad5 vectors.”

Since we have other COVID-19 vaccine options, I do not see why anyone would distribute an Ad5 vector vaccine in areas where men are at risk for HIV infection. If you are a man living in an area with high HIV prevalence and are at risk for HIV infection, talk to your doctor before you get your COVID vaccine. Ask your doctor if they're aware of the risks of the Ad5-based vaccine vectors and HIV infection, and see if there is an alternative vaccine that you can get for COVID-19. If none are available, I'm sure your doctor is going to talk to you about practicing safe sex and using condoms to help protect yourself from HIV.

So if you remember when I was talking about protein-based vaccines, we talked about the Australian vaccine, it was abandoned because of the little clamp that looked like an HIV protein and generated antibodies that looked like HIV antibodies, and made participants test positive for HIV antibodies. And this problem with the Ad5 vaccine vector and increased risk of HIV infection is why I'm hoping that somebody is taking that little clamp and looking at whether or not they can use something like that to generate an anti-HIV and anti-COVID vaccine. A combination vaccine for two viruses responsible for devastating pandemics would be a game changer for areas with vulnerable populations that are most disproportionately affected by these pandemics.

26:57 Ad5-based COVID-19 Vaccines in Clinical trials as of the date of this podcast
Okay, now, since I've been warning you against the adenovirus 5 vaccines if you're a male and high risk of HIV infection, I think I should go ahead and give you the information that we have right now on the Ad5 COVID-19 vaccines in development. Okay, first up, we have a vaccine called Sputnik V from the Gamaleya Research Institute in Russia. This vaccine uses the Ad5 vector and also an Ad26 vector, which is another human adenovirus vector. Ad26 is not as common as Ad5 so undoubtedly, they've added it to this formulation to try and help overcome at least a little bit of the pre-existing immunity to the Ad5 vector. An interesting aside here, the Gamaleya Research Institute in Russia is named after Nikolai Gamaleya, who was a pioneer in Russian microbiology. Now, Dr. Gamaleya wanted to learn Louis Pasteur’s technique for vaccinating people against rabies. So he went to Pasteur’s lab in Paris, where he learned how to do just that. And the two became colleagues and friends. And in fact, Pasteur was getting some pushback and sharp criticism of his technique. So he asked Gamaleya to defend his vaccination methods. Gamaleya then, of course, vaccinated himself thus proving that the method was safe for healthy individuals. Ah, the good old days, right? Okay, so back to the vaccines. So the Gamaleya research Institute's Sputnik V adenovirus vaccine is in phase III trials right now and has been authorized for early use in Russia, Belarus, and Argentina.

Chimp 28:31 Oxford AstraZeneca Adenovirus Vaccine
This next vaccine is not an Ad5-based vaccine but it's relevant to this Ad5 discussion, so I'm going to tell you about this one, and then explain what I mean by that. So the vaccine I'm referring to is the Oxford AstraZeneca vaccine that uses a chimpanzee adenovirus vector. The logic here is that a chimp adenovirus won't be common in humans. So pre-existing immunity won't be a problem. This seems like a reasonable idea. But even so, development of the Oxford AstraZeneca vaccine has been riddled with problems. On September 6 of 2020, the trials of the vaccine were stopped because a participant developed a condition called transverse myelitis, a serious neurological condition. Within about a week, the trials were restarted except for those in the US. Trials for this vaccine in the US took seven weeks to resume. And in that time, another person involved in the clinical trial also developed a severe neurological condition. And the reason it took seven weeks for the trial to resume in the US was apparently because the company was very slow in getting the documents to the FDA that were required to show that the vaccine was not in fact responsible for development of the neurological conditions.

Okay, so after that, Oxford and AstraZeneca experienced another problem. Turns out an error in measuring resulted in some trial participants receiving only half a dose of the vaccine for their first dose, instead of a full dose. And to make things even more interesting, this mistake resulted in a more effective immune response. Those who got two full doses of the vaccine showed the vaccine was 62% effective, but those with one half dose and one full dose showed the vaccine to be 90% effective. 

Researchers are trying to discern exactly why this happened but I think it has to do with the immunity generated against the vector. As I mentioned earlier, the first dose of a virus vector vaccine will induce immunity against both the target protein and the vector itself. It makes sense then that a larger first dose will cause the second dose to result in a stronger immune response against the vector thus blunting the immune response of the second dose to the target protein. This means that the smaller first dose would have a more effective second dose, resulting in greater vaccine efficacy for that group. Which is what they found. So here we have Oxford and AstraZeneca, with a fortuitous mistake that gives them data that shows a way to provide increased efficacy for an adenovirus vector vaccine. This is great. They really should have stopped there I think. 

For some reason, in December, Oxford and AstraZeneca decided to partner with Gamaleya to combine their chimp adenovirus vaccine with Gamaleya’s Sputnik V adenovirus vaccine, which if you remember, uses Ad5, plus ad26. This means… I'm sorry, but I just really don't understand this. This means that they're introducing Ad5 to their chimp adenovirus vaccine, that used a chimp adenovirus to avoid the Ad5-associated problems in the first place. Why would you do this? Okay, well, clearly, their logic is three different adenovirus vectors will generate immunity to three different vectors, but each of those vectors will generate immunity to the same target protein. So theoretically, the combination should give them an overall stronger immune response to the target SARS2 protein, and weaker immune responses to each of the different adenovirus vectors. Unfortunately, I think they're still going to be faced with pre-existing immunity to Ad5. So Ad5 will probably be cleared after each dose before it can really generate much of an immune response to the target protein. And they also have to consider what we recently learned about Ad5 and HIV acquisition if they introduce the Sputnik V vaccine to the AstraZeneca chimpanzee adenovirus vaccine. And this just doesn't seem like a smart move to me. Maybe I'll be wrong. It's happened. It's gonna happen again, maybe this is going to be it. And we're going to find out because they're starting a trial with this combination.

Now, let's be very clear. The Oxford AstraZeneca vaccine that is in phase III clinical trials right now, and has been authorized for emergency use in several countries, is strictly the Oxford AstraZeneca chimpanzee adenovirus vaccine. It is not in combination with anything at this point. If the Sputnik collaboration results in another vaccine, that will be an entirely separate process and vaccine with a new name, and new authorizations.

Okay, so let's get back to our Ad5 vaccines in development. So we have the Sputnik V, which we already talked about, and the potential collaboration of that with Oxford and AstraZeneca. Next on our list, we have an Ad5 vaccine called Convidecia. Probably mispronouncing that. This is a vaccine that's been designed by the Chinese company CanSino Biologics. This vaccine is currently in phase III trials and has been authorized for limited use in China. It is actually the only Ad5 COVID-19 vaccine in use at all at this time. You might remember that CanSino Biologics is the Chinese company that developed the Ad5 Ebola vaccine that is not licensed, but is authorized in China for emergency use and for stockpiling. It's the one with that significant caveat. You remember that one? The one that says their phase II trials did not demonstrate that it prevented Ebola.

 

All right, there are four more vaccines on our list that use Ad5, and these four are all in phase I clinical trials at the moment, and I'm a little embarrassed to say that three of the four are being produced by American companies. 

Dimi, why you do this to me? 
Oh my God, I've always wanted to say that.

And yes, this week was the attempted coup, and I am. Yeah, yeah.

Okay, so the first American company, racing to get us an amazing Ad5 vaccine is called VaxArt. And I hope they have something up their sleeve, because we don't have much information on that one right now. The next American company is called Immunity Bio. And their vaccine actually is a little more interesting. It's an Ad5 vaccine in phase I trials, but this one targets two virus proteins, the spike and the nucleocapsid. You know, that's a really great idea. I don't know why other vaccine companies aren't trying this right out of the gate. It's a great strategy to help prevent minor mutations in single proteins from rendering a vaccine ineffective. So it's really kind of a shame that Immunity Bio is using Ad5 for this one. Okay, Alt Immune is an American vaccine company that is doing something a little interesting that actually might help their vaccine candidate get around the Ad5 problems we've been discussing. And how might they do this, you ask? Well, their vaccine called AdCovid is using a different delivery system, it's not being injected. They're working on a nasal spray vaccine. A nasal spray vaccine is not systemic, like a vaccine that's injected into a muscle or under the skin is. This means the vaccine may be able to get around problems with pre-existing immunity to the vector, as well as maybe the risk of increased HIV infection that we've seen with Ad5 vectors. I'm looking forward to data from these trials. And hopefully, Alt Immune will give us a reason to be proud of an American adenovirus vaccine. And we've made it to the last Ad5 vaccine candidate in phase I trials. And this comes from a South Korean biotech company called Cellid. They are partnering with LG Chem, a South Korean chemical manufacturer, and their vaccine combines Ad5 with Ad35, another human adenovirus.

Well, that's it. Those are the other vaccine platforms that are in clinical trials right now for COVID-19. I know there's a lot of information here, and I will be providing links to relevant articles, websites, PDFs, and things of that nature on my website, as well as transcripts to every podcast episode. My website is heatherlander.com and if you click on podcasts, you will see each episode available for you to click on and each link will provide more information for that episode.

Okay, so, next time, I'm going to talk about virus evolution, and the mutations that we are seeing in SARS2 around the world, including the concerning ones that seem more transmissible. And we're going to discuss what those mean for vaccines. So I hope you check it out.

It's been a tough week, guys, and I'm wishing you all peace, love and critical thinking. Thanks for listening. Until next time, this is Dr. Heather Lander, reminding you to keep it in perspective.

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