7 ms·

Can you explain how it increases the breadth of antibody protection if the booster is exactly the same as the original shot? Is there any way to know whether t

Can you explain how it increases the breadth of antibody protection if the booster is exactly the same as the original shot? Is there any way to know whether that increased breadth of antibody protection isn't coming from a post vaccination exposure that wasn't tested for not tested? Since vaccinated people aren't generally required to do asymptomatic testing, let alone symptomatic testing in many places.

mlyle 5y ago
> Can you explain how it increases the breadth of antibody protection if the booster is exactly the same as the original shot? It's complicated! The short answer I gave elsewhere: B cells aggressively replicate and mutate in response to pathogens, and those that match are selected for. Repeating this process gets more B cells, but also broader varieties of resultant antibodies matching not just the original pathogen but things that are close to it. > Is there any way to know whether that increased breadth of antibody protection isn't coming from a post vaccination exposure that wasn't tested for not tested? Yes. We collect plasma from people, and then test it against a variety of variants in assays. We have plenty of old plasma to do this with. Indeed, there's some evidence that many people who were both infected with SARS-CoV-1 and subsequently vaccinated against SARS-CoV-2 may have exceptionally broad immunity to coronaviruses, not isolated to just SARS-CoV variants but also to wild-type coronaviruses circulating in animals and human coronaviruses causing the common cold.
- yonaguska 5y ago
  Thanks! This clears up a lot for me.
- flatiron 5y ago
  I want to compliment your responses. Factual and non aggressive which is needed in this time. Thank you.
  - mlyle 5y ago
    Hey, thank you so much! I try. I also have to confess that my understanding of this subject matter is far from perfect (and even experts' understanding is relatively limited).
- headsoup 5y ago
  I thought that was what these vaccines specifically don't do: they select for the spike protein of the original variant and ignore others, whereas natural infection generates a broader response that will target a variety of proteins. Has that changed?
  - smnrchrds 5y ago
    It's something I have seen a lot of people say here on HN, but I don't know if it's true. If having the whole virus was more effective than just the spike protein, wouldn't Sinopharm and Sinovac—which are inactivated virus vaccines—be more effective than Pfizer and Moderna? We still don't know their efficacy against Omicron, but they were less effective than mRNA vaccines against all previous variants.
    - headsoup 5y ago
      Initially perhaps, but do we have good longer term data on how the sinovac holds up, given we're now saying Pfizer needs to be 3-monthly and Moderna is a much stronger dose? I think there was some over-selling of the mRNA vaccines that needs strong follow-up review given the state of the virus vs last year without vaccines with a more potent variant.
      - smnrchrds 5y ago
        We won't have long-term data until a long time had passed, but so far, it doesn't seem inactivated virus vaccines fare any better than mRNA ones. https://www.nature.com/articles/d41586-021-02796-w https://www.nature.com/articles/d41586-021-02796-w
  - mlyle 5y ago
    What you're saying here isn't untrue, but it's nuanced and I think it misses some of the clear distinction. > they select for the spike protein of the original variant and ignore others Repeated exposure causes you to get many different kinds of antibodies that react against many things like the original spike protein. There's ample research showing that a 2 shot (and 3 shot) series of mRNA vaccination creates a very broad response that cross-reacts to many spike protein variants. Reaction against the spike protein is best, because this binding doesn't just activate the rest of the immune system, but it's neutralizing against the virus: it prevents its entry into cells. Compare this figure: https://cdn.jamanetwork.com/ama/content_public/journal/jama/938696/jld210021f1_1620430716.03243.png?Expires=1643331214&Signature=rz8bX-qJI3d7tkA5NEoxkkNRkng1o61I6BFjex8xJqgcCSt1x3GHNKXwlnuDTBGUgxqSzarDwB4qaL8lifemA5AZXAhRveLWD1vhphX~tierYtKPCo3xxvaKbs6iaAQnqwbCsne3rK0dn~xfrlTu8T77xTLhaW0BiE9raVb0Jxydve3P8aFGehxq5JGRURXt4~3EatE7eQAifu73Ri3PRHLFCldEPUSvNHVmsA-BvjCD9cbOsHgSP38ku-oT2PkoV4d~bZ7K5He4bLdnjUeCH1epOkHA~x30m2JIWcjDp~byTmhDTmCRB6he4Wu4omm8VkUfJUz8BhU4Bz4egbLzmQ__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA https://cdn.jamanetwork.com/ama/content_public/journal/jama/... Many convalescent (prior infected) individuals had very low neutralization activity against variants. All vaccinated individuals had good neutralization titers against all variants measured in this study, though they were still definitely better against A.1 than other types. > whereas natural infection generates a broader response that will target a variety of proteins. Natural infection will generate a variety of nucleocapsid antibodies, too (against non-spike portions of the virus). This is a mixed bag: it means the immune system can be activated and it also means that the immune system will try and break down things that have antibodies bound elsewhere on the virus... but the spike antibodies around that could directly prevent infection of new cells are less effective against variants.

mlyle 5y ago

> Can you explain how it increases the breadth of antibody protection if the booster is exactly the same as the original shot? It's complicated! The short answer I gave elsewhere: B cells aggressively replicate and mutate in response to pathogens, and those that match are selected for. Repeating this process gets more B cells, but also broader varieties of resultant antibodies matching not just the original pathogen but things that are close to it. > Is there any way to know whether that increased breadth of antibody protection isn't coming from a post vaccination exposure that wasn't tested for not tested? Yes. We collect plasma from people, and then test it against a variety of variants in assays. We have plenty of old plasma to do this with. Indeed, there's some evidence that many people who were both infected with SARS-CoV-1 and subsequently vaccinated against SARS-CoV-2 may have exceptionally broad immunity to coronaviruses, not isolated to just SARS-CoV variants but also to wild-type coronaviruses circulating in animals and human coronaviruses causing the common cold.

yonaguska 5y ago
Thanks! This clears up a lot for me.
flatiron 5y ago
I want to compliment your responses. Factual and non aggressive which is needed in this time. Thank you.
- mlyle 5y ago
  Hey, thank you so much! I try. I also have to confess that my understanding of this subject matter is far from perfect (and even experts' understanding is relatively limited).
headsoup 5y ago
I thought that was what these vaccines specifically don't do: they select for the spike protein of the original variant and ignore others, whereas natural infection generates a broader response that will target a variety of proteins. Has that changed?
- smnrchrds 5y ago
  It's something I have seen a lot of people say here on HN, but I don't know if it's true. If having the whole virus was more effective than just the spike protein, wouldn't Sinopharm and Sinovac—which are inactivated virus vaccines—be more effective than Pfizer and Moderna? We still don't know their efficacy against Omicron, but they were less effective than mRNA vaccines against all previous variants.
  - headsoup 5y ago
    Initially perhaps, but do we have good longer term data on how the sinovac holds up, given we're now saying Pfizer needs to be 3-monthly and Moderna is a much stronger dose? I think there was some over-selling of the mRNA vaccines that needs strong follow-up review given the state of the virus vs last year without vaccines with a more potent variant.
    - smnrchrds 5y ago
      We won't have long-term data until a long time had passed, but so far, it doesn't seem inactivated virus vaccines fare any better than mRNA ones. https://www.nature.com/articles/d41586-021-02796-w https://www.nature.com/articles/d41586-021-02796-w
- mlyle 5y ago
  What you're saying here isn't untrue, but it's nuanced and I think it misses some of the clear distinction. > they select for the spike protein of the original variant and ignore others Repeated exposure causes you to get many different kinds of antibodies that react against many things like the original spike protein. There's ample research showing that a 2 shot (and 3 shot) series of mRNA vaccination creates a very broad response that cross-reacts to many spike protein variants. Reaction against the spike protein is best, because this binding doesn't just activate the rest of the immune system, but it's neutralizing against the virus: it prevents its entry into cells. Compare this figure: https://cdn.jamanetwork.com/ama/content_public/journal/jama/938696/jld210021f1_1620430716.03243.png?Expires=1643331214&Signature=rz8bX-qJI3d7tkA5NEoxkkNRkng1o61I6BFjex8xJqgcCSt1x3GHNKXwlnuDTBGUgxqSzarDwB4qaL8lifemA5AZXAhRveLWD1vhphX~tierYtKPCo3xxvaKbs6iaAQnqwbCsne3rK0dn~xfrlTu8T77xTLhaW0BiE9raVb0Jxydve3P8aFGehxq5JGRURXt4~3EatE7eQAifu73Ri3PRHLFCldEPUSvNHVmsA-BvjCD9cbOsHgSP38ku-oT2PkoV4d~bZ7K5He4bLdnjUeCH1epOkHA~x30m2JIWcjDp~byTmhDTmCRB6he4Wu4omm8VkUfJUz8BhU4Bz4egbLzmQ__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA https://cdn.jamanetwork.com/ama/content_public/journal/jama/... Many convalescent (prior infected) individuals had very low neutralization activity against variants. All vaccinated individuals had good neutralization titers against all variants measured in this study, though they were still definitely better against A.1 than other types. > whereas natural infection generates a broader response that will target a variety of proteins. Natural infection will generate a variety of nucleocapsid antibodies, too (against non-spike portions of the virus). This is a mixed bag: it means the immune system can be activated and it also means that the immune system will try and break down things that have antibodies bound elsewhere on the virus... but the spike antibodies around that could directly prevent infection of new cells are less effective against variants.