Vaccine and variant talk

Jelly beans.

Up at my internship we have been preparing a presentation on the vaccine for our seniors. We're trying to refine the message for how to get people to understand the vaccine and COVID variants in a silly analogy that isn't too far off scientifically.

Every human is different. We recognize each other's humanity but we all can recognize someone as a fellow human. It is like potato salad in a way - everyone's family has gotten used to it in their particular way, however your grandma used to make it, etc. But as different as they may be, it is still recognizable as potato salad. For the most part, some things belong in it and some things just don't.

So, the vaccine causes new proteins (the spike protein of the COVID virus) to be made and they can be sprinkled on the salad but not make a fundamental change in the recipe. Maybe croutons, maybe someone hates broccoli, I know I wouldn't want Brussels sprouts on it, and so on. They don't belong but those things are mostly the same.

But what about jelly beans? Would seeing jelly beans in potato salad cause a big reaction? If they do, they might be funny as an example because they can come in different colors yet still don't belong. This is like how variants of the COVID virus appear. They might look a little different and be harder to detect but the antibodies still have a good chance to recognize them as plain wrong. It needs to be something that would get people to think "HELL NO!" but funny so the analogy is memorable and doesn't scare people off.


The seniors I encounter as co-chair of the Maplewood Seniors Advisory Committee and Maplewood senior representative member of the management team for SOMA Two Towns For  All Ages fully understand what a variant is and the concept scares them.  Quite a few have been able to get an appointment for the vaccine and of this group, many have received their first or second shot by now.  They thought, or at least hoped, that they would get the 90%+ immunity as a result.  Now they are beginning to realize this might not be the case.  They don't need jelly beans or potato salad, they need someone to tell them the truth about their chances of having to receive yet another shot or booster to protect them from the new variants that are emerging.  Honestly over fun presentation is what they need and want.


My sense is that your intentions are good, but the examples you are using make the matter even more obscure.   I would explain simply that the proteins on the virus can change over time and this is called a variant.  We all understand children so, perhaps a better way is to say that most viruses are like identical twins.   But sometimes you have fraternal twins that are very much the same but may have different colored hair.   

It is always good to have a joke or two when making a presentation.   So a "why did the chicken cross the road" joke is always good.  


I also think it may important for some seniors to learn that animals such as chickens, bats, raccoons can also be infected with viruses just like people.  As we know, usually the viruses stay just in the birds or bats, but that sometimes the virus can change and become infective to humans.   This is when trouble can start for us humans.... ...   I do not know your exact group or what you want to educate about, but this is what my experience has shown that non biologically educated people need to know.   Also, do not underestimate the education and knowledge of your audience.  Be prepared for in-depth questions.   (Hope this is helpful.)  


Oh, I have all the medical terminology and serious presentation materials I need. Those are the things that can be somewhat confusing and scary if one is not already immersed in such detail. And I can hold my own with any audience except for maybe epidemiologists and virologists at scientific meetings.

I am looking for alternatives to information that puts people to sleep or turns them off because it is technical, thus keeping them in the dark. If they have to work hard to overcome confusion you're not reaching them well. If you have a humorous analogy your audience can hold onto it is easier to introduce more detail. With this approach, they're more likely to understand the potential to have more variation in RNA viruses because making copies of mRNA does not have the same biochemical validation steps that DNA viruses have when they are replicated.

It's a little like the baseball uniform example I worked on. I already know how you get from cartoonish images to actual scientific understanding.


You have me interested.   Can you let us all know how well the presentation went?   I have some friends who are knowledgeable and smart, but they refuse to get vaccinated.   This is sad for them.   


It's not all funny stuff though. Indeed, variants can have more functionally dangerous changes instead of just disguises.

A New Coronavirus Variant Is Spreading in New York, Researchers Report

https://www.nytimes.com/2021/02/24/health/coronavirus-variant-nyc.html

"A new form of the coronavirus is spreading rapidly in New York City, and it carries a worrisome mutation that may weaken the effectiveness of vaccines, two teams of researchers have found.

The new variant, called B.1.526, first appeared in samples collected in the city in November. By the middle of this month, it accounted for about one in four viral sequences appearing in a database shared by scientists."


This short paper has a few worrisome points that I'll make notes on in later posts.

SARS-CoV-2 lineage B.1.526 emerging in the New York region detected by software utility created to query the spike mutational landscape


https://www.biorxiv.org/content/10.1101/2021.02.14.431043v2.full.pdf+html

TL;DR (and believe me, I'd understand if you didn't want to):

This ain't over. Keep wearing those masks. Make sure they're snug and cover your mouth AND your nose. And that word from the CDC about double masking? Yeah, unless you have a great single mask with multi-layer and other good attributes, double up.


An easy way to make those flimsy paper masks a little more effective.
https://www.bicycling.com/health-nutrition/a35597333/how-to-make-your-mask-more-effective-coronavirus/?utm_medium=social-media&utm_source=facebook&utm_campaign=socialflowFBBI&fbclid=IwAR3zA8VURDiZ6UtRQnLvht_FhnB_WPQkxLw838hSJtjvrhs_Nda6YuvBSOA

This was brought to my attention by an old Michigan friend who still rides. He was just bragging on his other alma mater's innovation.

Here's the link to the short video demonstrating the method.

;feature=youtu.be

Results (from the B.1.526 variant paper) 

Using the vdb tool, we detected several clusters of isolates (unrelated to variants B.1.1.7,

B.1.351, B.1.1.248, and B.1.429; Rambaut et al., 2020b; Faria et al., 2021; Tegally et al., 2020;

Zhang et al., 2021) with spike mutations at sites known to be associated with resistance to

antibodies against SARS-CoV-2 (Gaebler et al., 2021; Wang et al., 2021) (Table 1). This program

can find clusters of isolates sharing identical sets of spike mutations, and then these patterns

can be used to find potentially related isolates. One notable cluster of isolates was collected

from the New York region and represents a distinct lineage, now designated as B.1.526

(Figure 1). There are two main branches of this lineage, one having E484K and the other

including S477N, both located within the receptor-binding domain (RBD) of spike (Figure 2 and

Supplementary Table S1). Regarding four of the mutations in isolates in this lineage: 

------------------------------------------------------------------------------


(1) E484K is known to attenuate neutralization of multiple anti-SARS-CoV-2 antibodies, particularly thosefound in Class 2 (Gaebler et al., 2021), and is also present in variants B.1.351 (Tegally et al., 2020) and P.1/B.1.1.248 (Faria et al., 2021)

My take:

The E484K variant is able to escape many different kinds of antibodies, both made in the lab as well as those produced in humans that contract COVID-19. Three different articles they reference describe how some variants are not stopped by convalescent plasma from COVID survivors. So, the antibodies that saved those survivors weren't able to stop these variants. The human immune response starts out as an all-out attack in terms of the kind of antibodies we make. Those are called polyclonal antibodies - many antibodies that are developed to attack any part of the whole virus they can grab. We make some immune cells that remember how to make some of them and those cells gear up and make more of those antibodies if we get infected again - or vaccinated.


(2) D253G has been reported as an escape mutation from antibodies against the N-terminal domain (McCallum et al., 2021)

My take:

This is another observation of a COVID variant that antibodies don't recognize but the difference is that the N-terminal domain of the spike protein is away from its receptor-binding domain.

The spike protein is actually a trimer (it has 3 different parts) and the S1 part has the receptor-binding domain, the sticky part you hear about that grabs the angiotensin-converting enzyme 2 (ACE2) which is exposed on the outer surface of some of our cells. Mutations can change how well this part of the spike protein grabs it. Some make it better at that task and those are worrisome mutations. Antibodies form against this part, which is fortunate because they not only grab it, they grab it on the business end - the part the virus depends on to uh, stick the landing. [sorry]

[If you know this stuff already, forgive me for the biochem notes] 

Amino acids are like the bricks that build proteins and they have a nitrogen (N) atom on one end and a carbon (C) atom on the other end. They get linked up by enzymes that read messenger RNA strands and make a bond attaching the C side of one amino acid to the N side of the next amino acid, and so on and so on until the mRNA strand of directions is finished. The N-terminal of a protein refers to the start of the amino acid string (a polypeptide) that has the nitrogen atom (N) on the first amino acid sticking out since it does not have another amino acid linked to it on that side. The other end of a protein chain is called the C-terminal because that final amino acid has a carbon atom sticking out on the end for the same reason. 

Anyway, the 3-dimensional shape around the N-terminal gets named the N-terminal domain (duh) and they have found that this part of the S1 part serves as another important part of the spike protein for antibodies to grab. They have made antibodies in the lab to selectively bind just that region and they are useful as a tool in some experiments. This observation shouldn't come as a surprise but it is worrisome that this "back up site" can have changes that disguise it well enough to make laboratory-produced antibodies miss it when we know they *should* nail it.


(3) S477N has been identified in several earlier lineages (Hodcroft et al., 2020), is near the binding site of multiple antibodies (Barnes et al., 2020), and has been implicated to increase viral infectivity through enhanced interactions with ACE2 (Chen et al., 2020; Ou et al., 2020)

My take:

The 477th amino acid that is the site of the mutation S477N is in the receptor-binding domain of the COVID spike protein. It is also an important region for antibodies to grab. That change does two things and they both suck. It causes it to be harder for antibodies to recognize the spike protein and it also makes the spike protein grab ACE2 better. Well, ****.


(4) A701V sits adjacent to the S2’ cleavage site of the neighboring protomer and is shared with variant B.1.351 (Tegally et al., 2020). The overall pattern of mutations in this lineage (Figure 2) suggests that it arose in part in response to selective pressure from antibodies. 

My take:

This last statement reminds us about an aspect of natural selection I wish this virus didn't follow. All those 'typos' in the mRNA copying process make mutations and I think we in the non-science world were thinking of it like "Oh well, mistakes are gonna happen. Let's hope they're just random..." There's a reason the scientists decided to make that statement about selective pressure from antibodies, the virus is getting a boost from the "survival of the fittest" routine. Infecting humans as well as it does has been like COVID-19 going to summer camp for computer programmers. All kinds of new stuff gets invented in hack-a-thons because people love to compete against one another. Yeah, it is anthropomorphizing the virus too much but it suits the analogy.

The mRNA copying process tends to have mistakes that produce lots of variants and there is data indicating we humans might be speeding the appearance of new variants that are more likely to survive. First, there is our own immune response to an actual infection that is not always effective. Surviving variants that escape a sick person's antibodies and go on to get transmitted somehow might also be better at evading another person's immune system. Then there are the vaccines we are relying on right now. Those vaccines are also putting selective pressure on the virus - a vaccinated person can still get infected with COVID-19 and before they get over it they may spread it if they're not still being careful. 

Yes, the virus is more easily attacked by a vaccinated person's primed immune system but some new virus replicants may have escaped the infected person. And the verb 'escape' is definitely not in the past tense these days. Until we can slow its spread by getting most people vaccinated this phenomenon will continue. We already accept that with the influenza virus and we might have to with COVID-19 as well.


Why do some people wind up with huge bodily trauma from a COVID infection while others in that same household get the same virus and don't have bad symptoms at all?

I've always wondered this and was too lazy to look for research on it but found it while I was looking at the Times article. Researchers at Stanford appear to have found an important clue. The more a person makes antibodies that attack the spike protein, the better they can fend off COVID and have a much easier time getting over it. There are other parts of the virus besides the spike protein that antibodies do get made against and but those parts aren't as critical to the viral assault. So far the message appears to be - stop the key step of binding ACE2 so the virus cannot grab ahold of the human cells.

From the article:

“Although previous studies have assessed the overall antibody response to infection, we compared the viral proteins targeted by these antibodies,” Boyd said. “We found that the severity of the illness correlates with the ratio of antibodies recognizing domains of the spike protein compared with other nonprotective viral targets. Those people with mild illness tended to have a higher proportion of anti-spike antibodies, and those who died from their disease had more antibodies that recognized other parts of the virus.”

https://med.stanford.edu/news/all-news/2020/12/study-identifies-difference-between-severe-and-mild-covid-19.html


SARS-CoV-2 evolution and vaccines: cause for concern?

 and 

    Published:January 29, 2021 DOI:https://doi.org/10.1016/S2213-2600(21)00075-8

    https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00075-8/fulltext

    This is a pretty good discussion about how the virus changes and how the vaccines are performing. It also discusses T-cell mediated immunity. That's when T-ymphocytes grab the virus, kill it and take it apart and use those remnants to teach B-lymphocytes how to make antibodies against them as well as make T-killer cells & macrophages kill the virus. Those T-helper cells, they're such good little helpers. We hear about antibodies all the time but let's give those T cells some love.

    From the paper:

    Ultimately, most vaccines are based on a recombinant spike protein sequence. Thus if evidence emerges that particular variants do appear to influence vaccine efficacy, it should be possible to periodically reformulate the vaccines so that they better match the circulating strains. Importantly, the overall effectiveness of immunization will correlate with rates of vaccine uptake. We therefore encourage researchers, health-care providers, and policymakers to act as advocates for immunization, and to advise individuals with questions about vaccines to seek this information from reliable sources. The higher the proportion of a population vaccinated, the lower the number of susceptible individuals, and the fewer opportunities SARS-CoV-2 will have to spread and mutate.



    mtierney said:

    Back in 1964....

    https://apple.news/ANgqto91HTl2hjqejtDgaFg

     I remember being told about this in biochemistry class at Michigan! PCR was getting started as it was like some magic elixir.


    bikefixed said:

    Why do some people wind up with huge bodily trauma from a COVID infection while others in that same household get the same virus and don't have bad symptoms at all?

    I've always wondered this and was too lazy to look for research on it but found it while I was looking at the Times article. Researchers at Stanford appear to have found an important clue. The more a person makes antibodies that attack the spike protein, the better they can fend off COVID and have a much easier time getting over it. There are other parts of the virus besides the spike protein that antibodies do get made against and but those parts aren't as critical to the viral assault. So far the message appears to be - stop the key step of binding ACE2 so the virus cannot grab ahold of the human cells.

    From the article:

    “Although previous studies have assessed the overall antibody response to infection, we compared the viral proteins targeted by these antibodies,” Boyd said. “We found that the severity of the illness correlates with the ratio of antibodies recognizing domains of the spike protein compared with other nonprotective viral targets. Those people with mild illness tended to have a higher proportion of anti-spike antibodies, and those who died from their disease had more antibodies that recognized other parts of the virus.”

    https://med.stanford.edu/news/all-news/2020/12/study-identifies-difference-between-severe-and-mild-covid-19.html

     @bikefixed 

    So, am I interpreting correctly that it may have been a stroke of good luck to have mRNA vaccines, as they help prime immune systems to have antibodies targeting the spike protein?  

    ETA: Or maybe that is why the mRNA vaccines performed well in clinical trials, and moved to the top of the vaccine approaches?


    Regarding tying a knot in the ear loop - this is even easier than it looks in the video, and really pulls the mask much more firmly against my face/cheeks/chin, a good thing!

    Unfortunately, it also makes the loop short enough that it pulls out from behind my ear (or in one case, pulled out of the mask).  Pretty crowded back there with 2 mask loops and my glasses.  Hoping for further innovation....


    if you have an audience to discuss a very serious topic and you’re discussing potato salad and jellybeans you’re not going to be taken very seriously.


    You don't know my audiences.

    Redfruit said:

    if you have an audience to discuss a very serious topic and you’re discussing potato salad and jellybeans you’re not going to be taken very seriously.


    mjc said:

    Regarding tying a knot in the ear loop - this is even easier than it looks in the video, and really pulls the mask much more firmly against my face/cheeks/chin, a good thing!

    Unfortunately, it also makes the loop short enough that it pulls out from behind my ear (or in one case, pulled out of the mask).  Pretty crowded back there with 2 mask loops and my glasses.  Hoping for further innovation....

     I had that (or rather, still do) issue with some masks that are more of a permanent nature. I was able to make them fit better with my own one-off adjustments. I've improvised an elastic strip with hooks on either end to grab the mask loops for the paperish masks if I don't have one of my regulars with me. It took a while to find the right length though.


    sprout said:

     @bikefixed 

    So, am I interpreting correctly that it may have been a stroke of good luck to have mRNA vaccines, as they help prime immune systems to have antibodies targeting the spike protein?  

    ETA: Or maybe that is why the mRNA vaccines performed well in clinical trials, and moved to the top of the vaccine approaches?

    Yes, on the good fortune of already having done research investigating the ability to use mRNA to make vaccines to target selective regions of some antigen or microbial invader. Before, especially if you weren't able to determine the functional parts of your target, you had to do the laboratory work to come up with many different antibodies and then figure out which of them did what you were hoping for.

    Since scientists were able to quickly determine the means by which COVID-19 invades our cells, they were able to cut out most of the hunting around for the right parts of the virus to try and grab with antibodies. Since it is pretty easy to get the genetic info for viruses - they rely on the host's DNA replication and/or mRNA translation processes - they could quickly how to make a more stable synthetic mRNA strand to code for the part of the whole virus genome they wanted to use as the target. They narrowed down how much of the mRNA was needed from that specific location and then it was easy to make the spike protein alone.

    Of course, that's the grandest of simplifications, but you're right. Because this kind of trick was dreamt up and tried some 10 years ago there was enough time to refine the process to the point where it only took months to get several candidate vaccines to do clinical tests with. So much of the weeding out process in the lab is not necessary anymore when they're trying to come up with how to get exactly what they want to attack with a vaccine.


    bikefixed said:

    You don't know my audiences.

    Redfruit said:

    if you have an audience to discuss a very serious topic and you’re discussing potato salad and jellybeans you’re not going to be taken very seriously.

     I will admit that your jellybean and potato salad analogy lost me completely, both as a civilian and as someone who used to work in a virology lab... 


    susan1014 said:

     I will admit that your jellybean and potato salad analogy lost me completely, both as a civilian and as someone who used to work in a virology lab... 

    Sigh. Potato salad represents the human body. There are many different recipes but it is still potato salad. The jelly beans represent COVID particles. Jelly beans do not belong on potato salad. Funny how I didn't need to say that last part.

    I brought up the COVID virus and vaccine stuff and there were blank looks and bored faces. As soon as I put it in that analogy, the room brightened up. I could then go back to more technical terms and refer back to those things.

    ETA: This group was at a senior housing facility in Paterson. Another intern was with me translating into Spanish. It was pretty good, based on the number of people that stayed and kept asking questions on the session (good thing we had a pro license). I taught them that mask trick. Bottom line, there was probably better safety behavior or at least the favorable sentiment for the next couple of hours. There wasn't any trash talk about the vaccine, unlike the stuff said while milling around waiting for us to start.


    Kudos to bikefixed.  It looks like her analogy worked!  Health education is tremendously important.  


    mjc said:

    Regarding tying a knot in the ear loop - this is even easier than it looks in the video, and really pulls the mask much more firmly against my face/cheeks/chin, a good thing!

    Unfortunately, it also makes the loop short enough that it pulls out from behind my ear (or in one case, pulled out of the mask).  Pretty crowded back there with 2 mask loops and my glasses.  Hoping for further innovation....

     In addition to glasses, I wear hearing aids and it gets pretty crowded on the ear! Innovations are appearing on amazon, but I crocheted a head band and sewed buttons on each side for the mask straps. Ears stay warm, and hearing aids and eye glasses are Protected in place.


    Ooh, that's nice! I've seen some innovations similar to that. Got some pics?

    mtierney said:

     In addition to glasses, I wear hearing aids and it gets pretty crowded on the ear! Innovations are appearing on amazon, but I crocheted a head band and sewed buttons on each side for the mask straps. Ears stay warm, and hearing aids and eye glasses are Protected in place.

     


    RobertRoe said:

    Kudos to bikefixed.  It looks like her analogy worked!  Health education is tremendously important.  

     The other analogy to COVID variants using the baseball uniforms has a limited appeal but it has made a few people chuckle. This potato salad thing seemed to work better because more people had some sort of investment in their mom's (or some other loved relative's) recipe. Something that besmirches that beloved dish by its mere presence just seems funny and atrocious at the same time. We want that vaccine to make our immune system have this kind of appreciation for jelly beans (someone also thought croutons would be similarly out of place) when it sees them.



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