The next big scientific discussion bubbling to the surface is the potential of another booster: Will SARS-CoV-2 continue to mutate to escape antibody protection? Do we need another booster? If so, what’s the next formula?
Fascinating story. I read that US Army is heading to Phase II with a pancoronavirus vaccine. Would such a vaccine obviate the need for future boosters? Meanwhile, I simply don't get the slow-mo for giving more current boosters. Boosters will save at least SOME lives with 100% certainty. So what's the downside, and how can that possibly compare with lives saved?
yes, such a vaccine like the pancoronavirus would be a game changer! I wrote a post with Eric Topol about this here (https://yourlocalepidemiologist.substack.com/p/pan-coronavirus-super-vaccine). I think one downside to just multiple ongoing boosters is dissemination and uptake. we are already having an impossible time having people get the booster now. do we "save" our efforts and messaging until we *really* need one? its a good question
Too bad we can't make getting a booster sound like it's something exclusive, unavailable to Trump supporters. They'd be storming the clinics to get what is rightfully theirs.
Other than logistical challenges, are there biological or medical reasons not to create many boosters? I have seen the claim online that "too many" mRNA shots leads to "immune exhaustion" or something, but so far I have only seen hand-waving claims about it and no hard data.
What exactly did you mean by your word "mutating" as used in the sentence: "In addition, T-cells, our second line of defense that keeps us out of the hospital, are mutating but have much less evolutionary pressure than our first line of defense (antibody protection)." I must have been sleeping in medical school on the day some professor covered T-cell biology, but I don't think human T-cells mutate so much. And it is not cells that mutate anyway, it is genetic material per se where mutations would occur. What am I missing here?
I was also going to comment on this. I think she meant something like "The antigens recognized by T-cells, our second line of defense that keeps us out of the hospital, are mutating but have much less evolutionary pressure than the antigens recognized by our first line of defense (antibody protection)." That's a mouthful of a sentence, so I suspect it got broken during some editing rewrite (a functional mutation itself (heh)).
Unless I'm missing something, T-cells themselves should not be replicating, and thus any mutations that they do somehow pick up die with the T-cell itself. The evolutionary pressure is on the antigens presented due to viral infection (i.e. in the viral genome rather than the T-cells), and there I believe she's right that the evolutionary pressure is stronger on the antibody-associated antigens. It might be interesting to dig a bit more into why that pressure is different, but I think it's intuitive that unless the virus can make it past the first line of defense (antibodies), making it past the second line of defense (T-cells) is basically irrelevant.
Out of curiosity, now that we know that mix-and-match vaccines of different brands is safe (e.g. j&j then pfizer) and generates good antibody response, does this mean that getting 3 different kinds/brands of vaccines is also safe? (For example: inactivated vaccine + vector-based+ mrna)
Very helpful and informative. Thank you for assembling this information.
One point to bear in mind is the mRNA vaccines (Pfizer BioNTech and Moderna) are unlike traditional vaccines. Traditional vaccines use whole virus, which display a very large number of features (epitopes). In the case of influenza, the surface glycoproteins display a wide range of features that are not essential, meaning that a lot of them can change without impacting the function of the enzymes (neuraminidase and hemagglutinin). But these features are recognized by the antibodies. Thus a mutation that alters antibody recognition may still be viable.
Both mRNA vaccines are specific to the receptor binding domain (RBD) on the Spike protein. Binding to the receptor is vital for the virus to infect cells, and the hope is that changes in the sequence of the RBD that would escape immune recognition will not be infectious. That was the plan, and, so far, it seems to be working. That is, the mRNA vaccines have protected against a wide range of variants. Of course it is early in the pandemic, and ooutcomes may change rapidly. I would offer that we should bear in mind that the mRNA vaccines may behave differently than other, more traditional vaccines. This complicates comparisons of vaccine trials from around the globe.
#Gabriel, are you asking whether the virus suddenly found millions of hosts to replicate in, so even if mutations (variants) occur with low probability per virus particle, we'd expect to see quite a few variants among the entire (planetary) viral population?
We are starting to get close to the 6 month mark in the US for non immunocompromised adults since the first booster. Will there be an official recommendation to get another booster 6 months apart?
What I’m wondering is does the most promising antiviral (Paxlovid) lose efficacy (like vaccines do) as the virus mutates or is it “built to last” through many mutations?
I have a booster question: my insurance didn't start boosters until weeks AFTER it was recommended to get one, so I got a shot somewhere else. I've come to learn what I got was a first dose of Pfizer, which is slightly less than the booster dose. Am I still considered boosted, or should I get a "real" one at this point?
I'm surmising you received the Moderna vaccine for your primary series? So the Moderna booster would be 50 μg vs. the dose of Pfizer (primary and booster) would be 30 μg. Is that correct?
The dose of the Pfizer vaccine (30 μg) is the same for the primary vaccinations (doses 1 and 2, as well as 3 if immunocompromised) as it is for the booster. Only the Moderna booster (50 μg) is a lower dose than the primary vaccinations (100 μg).
On our records when we received Moderna booster it states "low dose Moderna 25 (something)". When we were at the site to get the booster they stated low dose booster is 25, immunocompromised is 50. I always thought it was 50 for booster, 100 for third dose (immunocompromised) with Moderna. So always been concerned we didn't get the right amount.
I believe, though, that I can offer some information that will be reassuring. What you likely saw were mL volumes of the vaccines used, not the doses of the active ingredient.
Yes, on my record it states that, but the nurses stated 25 for low dose booster, 50 for immunocompromised so they probably meant (I hope) what you mentioned and what the informative link you sent me (THANK YOU). :)
Wanting confirmation: immunocompromised who received 2 mRNA vaccines and a “3rd dose” shot should still go for a booster 5 months after the 3rd shot, right?
I believe that is correct. According to the CDC, for the immunocompromised age 5 and older, the 3rd shot (28 days or more after the 2nd shot) is part of the primary series and is not considered a booster shot. The CDC recommends a booster shot 5 months or more after having completed their primary series.
BA.2 was the lazy bored sibling of BA.1. If it was 1%-2% more contagious, why wasn’t it out-competing BA.1 from the beginning? Did it mutate, giving it a kick start, or did it’s favorite TV series finally end and it decided to join the action?
The graphics are especially helpful in understanding the situation. Thank you so much!
Fascinating story. I read that US Army is heading to Phase II with a pancoronavirus vaccine. Would such a vaccine obviate the need for future boosters? Meanwhile, I simply don't get the slow-mo for giving more current boosters. Boosters will save at least SOME lives with 100% certainty. So what's the downside, and how can that possibly compare with lives saved?
yes, such a vaccine like the pancoronavirus would be a game changer! I wrote a post with Eric Topol about this here (https://yourlocalepidemiologist.substack.com/p/pan-coronavirus-super-vaccine). I think one downside to just multiple ongoing boosters is dissemination and uptake. we are already having an impossible time having people get the booster now. do we "save" our efforts and messaging until we *really* need one? its a good question
Too bad we can't make getting a booster sound like it's something exclusive, unavailable to Trump supporters. They'd be storming the clinics to get what is rightfully theirs.
Other than logistical challenges, are there biological or medical reasons not to create many boosters? I have seen the claim online that "too many" mRNA shots leads to "immune exhaustion" or something, but so far I have only seen hand-waving claims about it and no hard data.
Thank you so much for laying this info out in a manner that I can understand and digest. I truly appreciate your work.
What exactly did you mean by your word "mutating" as used in the sentence: "In addition, T-cells, our second line of defense that keeps us out of the hospital, are mutating but have much less evolutionary pressure than our first line of defense (antibody protection)." I must have been sleeping in medical school on the day some professor covered T-cell biology, but I don't think human T-cells mutate so much. And it is not cells that mutate anyway, it is genetic material per se where mutations would occur. What am I missing here?
I was also going to comment on this. I think she meant something like "The antigens recognized by T-cells, our second line of defense that keeps us out of the hospital, are mutating but have much less evolutionary pressure than the antigens recognized by our first line of defense (antibody protection)." That's a mouthful of a sentence, so I suspect it got broken during some editing rewrite (a functional mutation itself (heh)).
Unless I'm missing something, T-cells themselves should not be replicating, and thus any mutations that they do somehow pick up die with the T-cell itself. The evolutionary pressure is on the antigens presented due to viral infection (i.e. in the viral genome rather than the T-cells), and there I believe she's right that the evolutionary pressure is stronger on the antibody-associated antigens. It might be interesting to dig a bit more into why that pressure is different, but I think it's intuitive that unless the virus can make it past the first line of defense (antibodies), making it past the second line of defense (T-cells) is basically irrelevant.
thanks. i was suspecting that some words got inverted during edits, etc.
Out of curiosity, now that we know that mix-and-match vaccines of different brands is safe (e.g. j&j then pfizer) and generates good antibody response, does this mean that getting 3 different kinds/brands of vaccines is also safe? (For example: inactivated vaccine + vector-based+ mrna)
Can you address the issue of whether the non-ladder-like mutation pattern is evidence for a lab-leak origin for omicron?
Very helpful and informative. Thank you for assembling this information.
One point to bear in mind is the mRNA vaccines (Pfizer BioNTech and Moderna) are unlike traditional vaccines. Traditional vaccines use whole virus, which display a very large number of features (epitopes). In the case of influenza, the surface glycoproteins display a wide range of features that are not essential, meaning that a lot of them can change without impacting the function of the enzymes (neuraminidase and hemagglutinin). But these features are recognized by the antibodies. Thus a mutation that alters antibody recognition may still be viable.
Both mRNA vaccines are specific to the receptor binding domain (RBD) on the Spike protein. Binding to the receptor is vital for the virus to infect cells, and the hope is that changes in the sequence of the RBD that would escape immune recognition will not be infectious. That was the plan, and, so far, it seems to be working. That is, the mRNA vaccines have protected against a wide range of variants. Of course it is early in the pandemic, and ooutcomes may change rapidly. I would offer that we should bear in mind that the mRNA vaccines may behave differently than other, more traditional vaccines. This complicates comparisons of vaccine trials from around the globe.
Couldn't variants during the acute pandemic phase be seen as evolutionary shrapnel after a relatively recent explosion?
#Gabriel, are you asking whether the virus suddenly found millions of hosts to replicate in, so even if mutations (variants) occur with low probability per virus particle, we'd expect to see quite a few variants among the entire (planetary) viral population?
Yeah. Whereas once we're out of the explosive growth phase we might not be as blindsided.
I'm into indeterminate forms
We are starting to get close to the 6 month mark in the US for non immunocompromised adults since the first booster. Will there be an official recommendation to get another booster 6 months apart?
What about the anti virals like paxlovid? Is their efficacy variant dependent?
What I’m wondering is does the most promising antiviral (Paxlovid) lose efficacy (like vaccines do) as the virus mutates or is it “built to last” through many mutations?
Thank you. Feels like a complete game changer if it’s really mutation proof.
I have a booster question: my insurance didn't start boosters until weeks AFTER it was recommended to get one, so I got a shot somewhere else. I've come to learn what I got was a first dose of Pfizer, which is slightly less than the booster dose. Am I still considered boosted, or should I get a "real" one at this point?
I'm surmising you received the Moderna vaccine for your primary series? So the Moderna booster would be 50 μg vs. the dose of Pfizer (primary and booster) would be 30 μg. Is that correct?
The CDC states that a booster of either of the mRNA vaccines is sufficient no matter which of the 2 mRNA vaccines you received for your primary series. See https://www.cdc.gov/coronavirus/2019-ncov/vaccines/booster-shot.html.
Ah, no. I had J&J first, which is why I felt like I needed to get a booster quickly, before my insurance caught up to whatever they were waiting for.
Got it.
The dose of the Pfizer vaccine (30 μg) is the same for the primary vaccinations (doses 1 and 2, as well as 3 if immunocompromised) as it is for the booster. Only the Moderna booster (50 μg) is a lower dose than the primary vaccinations (100 μg).
On our records when we received Moderna booster it states "low dose Moderna 25 (something)". When we were at the site to get the booster they stated low dose booster is 25, immunocompromised is 50. I always thought it was 50 for booster, 100 for third dose (immunocompromised) with Moderna. So always been concerned we didn't get the right amount.
I understand your concern.
I believe, though, that I can offer some information that will be reassuring. What you likely saw were mL volumes of the vaccines used, not the doses of the active ingredient.
See https://www.fda.gov/media/153354/download for details.
Yes, on my record it states that, but the nurses stated 25 for low dose booster, 50 for immunocompromised so they probably meant (I hope) what you mentioned and what the informative link you sent me (THANK YOU). :)
Wanting confirmation: immunocompromised who received 2 mRNA vaccines and a “3rd dose” shot should still go for a booster 5 months after the 3rd shot, right?
I believe that is correct. According to the CDC, for the immunocompromised age 5 and older, the 3rd shot (28 days or more after the 2nd shot) is part of the primary series and is not considered a booster shot. The CDC recommends a booster shot 5 months or more after having completed their primary series.
See https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html (last updated January 6, 2022).
What is your take on the risks / benefits of including the N-protein as a target of the vaccines?
Thank you for what you are doing, you are one of my favorite sources of pandemic information.
BA.2 was the lazy bored sibling of BA.1. If it was 1%-2% more contagious, why wasn’t it out-competing BA.1 from the beginning? Did it mutate, giving it a kick start, or did it’s favorite TV series finally end and it decided to join the action?