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?
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?
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.
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?
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?
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?
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?
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?
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?
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?
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?
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?
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?