8 ms·

I've not seen much reported in the way of clinical trials / peer-reviewed publications for modified vaccines that target (the spike protein of) these variants o

by lol768 5y ago

I've not seen much reported in the way of clinical trials / peer-reviewed publications for modified vaccines that target (the spike protein of) these variants of concern that are actively circulating. Is there ongoing work here I'm missing? What progress has been made? I'm somewhat surprised that almost a year on from the initial vaccination roll-out in the UK we're now dishing out boosters which are .. identical to the vaccinations given out initially.

angelzen 5y ago
That is a fantastic question. We are still vaccinating & boosting against the original variant. Would "the experts" please demonstrate that vaccines against variants are effective, given that original antigenic sin is a long known and well documented phenomenon? https://en.wikipedia.org/wiki/Original_antigenic_sin https://en.wikipedia.org/wiki/Original_antigenic_sin https://www.jstor.org/stable/985534 https://www.jstor.org/stable/985534
- belltaco 5y ago
  How is OAS related to ADE?
  - angelzen 5y ago
    A South Korea paper from 2016 argues they are related "sometimes". Note that coronaviruses are RNA viruses. Now, all the epi data we have indicates that the covid mRNA vaccines are effective against covid variants of concern. No need to panic. "Original Antigenic Sin Response to RNA Viruses and Antiviral Immunity" "Abstract: The human immune system has evolved to fight against foreign pathogens. It plays a central role in the body's defense mechanism. However, the immune memory geared to fight off a previously recognized pathogen, tends to remember an original form of the pathogen when a variant form subsequently invades. This has been termed 'original antigenic sin'. This adverse immunological effect can alter vaccine effectiveness and sometimes cause enhanced pathogenicity or additional inflammatory responses, according to the type of pathogen and the circumstances of infection. Here we aim to give a simplified conceptual understanding of virus infection and original antigenic sin by comparing and contrasting the two examples of recurring infections such as influenza and dengue viruses in humans." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5086450 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5086450
- blackbear_ 5y ago
  > Would "the experts" please demonstrate that vaccines against variants are effective There's plenty of evidence that current vaccines work against variants: - https://www.cdc.gov/mmwr/volumes/70/wr/mm7034e4.htm https://www.cdc.gov/mmwr/volumes/70/wr/mm7034e4.htm - https://www.nejm.org/doi/full/10.1056/NEJMoa2108891 https://www.nejm.org/doi/full/10.1056/NEJMoa2108891 - https://www.cell.com/cell/fulltext/S0092-8674(21)01057-6#%20 https://www.cell.com/cell/fulltext/S0092-8674(21)01057-6#%20 > given that original antigenic sin is a long known and well documented phenomenon? This could apply both to vaccines and natural infections. Not sure what you are trying to say?
  - MuffinFlavored 5y ago
    > There's plenty of evidence that current vaccines work against variants: Is there any reason to be afraid of getting vaccinated?
    - zzutz 5y ago
      besides the fact that plenty of European countries have banned the use of certain vaccines because of heart issues? besides the fact that Fauci is responsible for funding bio-terrorism in Wuhan? No not really.
    - didibus 5y ago
      > Is there any reason to be afraid of getting vaccinated? There's plenty of reasons, do you mean to also ask how likely other people on the internet believe each one to be? For example, if you ask me, this is my personal assessment: Reason 1 - Vaccines could also contain microchips or other device for tracking, brainwashing and remote manipulating my body and mind by whoever mastermind is in charge of what goes in them. I think that's very unlikely, I'd give it a 0.00000001% probability. I just dont know of any possibility for such advanced technology. And I can think of many different means that you can be more cost effectively tracked, manipulated or brain washed. I can also think of other ways they could have injected you with such things. Reason 2 - The vaccines will result in worst long terms negative effects on your health than getting Covid. I think this is a little more likely, but given all prior vaccines have shown to be quite safe, and even if they could be responsible for some long term effects, even some we haven't linked back to them yet, seeing as life expectancy and quality of life has grown year over year since the introduction of vaccines, it seems the equation would still play in their favor. There are also more and more literature linking prior viruses as a possible cause of long term negative effects like dimentia, various auto-immune diseases, etc. So it would seem Covid is more likely to introduce long term negative effects. So I'd give it a 1% chance. Reason 3 - The vaccines will result in worst short term effects on your health then getting Covid. I think this one has been shown that most of the time, Covid is more likely to kill you or make you really sick as compared to vaccines. I'd give this one a 0.0001% chance. Reason 4 - Vaccines can stop your pregnancy or your period and make you stink I have seen zero cases of this, and everyone who's had a vaccine to my nose do not smell, and still have period and can get pregnant. I'd give this one a 0.000000000000000001% chance. There might be more reasons, but those are the ones I've heard most often, and this is only my personal risk assessment.
- greg5green 5y ago
  They haven't found original antigenic sin so far. There's a couple links with some data (although I couldn't find a pre-print or published article right now) in this comment: https://news.ycombinator.com/item?id=29005187 https://news.ycombinator.com/item?id=29005187
  - angelzen 5y ago
    Thanks for the links! Note that they are making variant-specific vaccines, not proving that variant-specific vaccines are effective against the target variant, if delivered after the original vaccine. Side note: I hope we can do better than taking at face value investor press releases by the biopharma corps producing the vaccines.
    - greg5green 5y ago
      >Note that they are making variant-specific vaccines, not proving that variant-specific vaccines are effective against the target variant, if delivered after the original vaccine. You are correct that it isn't proving vaccine efficacy, but it is showing a different set of antibodies created by the variant vaccines that are more effective at neutralizing the targeted variant than the antibody collection created by the original, WT-targeted vaccine. >Side note: I hope we can do better than taking at face value investor press releases by the biopharma corps producing the vaccines. I hate science by press release too. I wish I was better at bookmarking the pre-prints and journal articles I find/read, but they'd just be a mess I couldn't find anything in either :|
- 323 5y ago
  OAS might be a problem with much more divergent future variants. Today's variant are still very close to the original, so OAS is not a factor yet.
greg5green 5y ago
I'm having trouble finding the paper, but I'm pretty I've seen a pre-print for mRNA-1273.351. This press release is the closest I could find on short notice: https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-positive-initial-booster-data-against-sars-cov https://investors.modernatx.com/news-releases/news-release-d... Novavax has also been working on a Beta variant booster (and I believe has moved on to a Delta booster that hasn't started NHP trials yet) -- here's some info from a presentation: https://www.novavax.com/sites/default/files/2021-05/NVAX-WVC2021-GregGlenn-FINAL.pdf https://www.novavax.com/sites/default/files/2021-05/NVAX-WVC... (It's slides 17 and 18) Pfizer/BioNTech definitely has a Delta booster getting ready for NHP trials, but my Google Fu is lacking today, apparently.
nextos 5y ago
I work at an immunology lab which is next door to most of the Oxford vaccine group. I think the quick (and overly simplistic) answer to this question is that models (e.g. convolutional networks) that predict which chunks of viral (or human) proteins are displayed to immune cells (HLA presentation), along with other kinds of models (like those predicting crossreactivity of T cell receptors against mutated epitopes) are really primitive (mostly because of low quality training datasets, it's not really a hard problem like e.g. protein folding). Hence, rushing a new vaccine is not easy as there is a lot of labwork to do. As a matter of fact, all COVID vaccine designs had essentially the same payload (the whole spike protein). Modern subunit vaccines would typically include only little chunks of the spike (to increase efficiency and avoid side effects). But this was not trivial to do quickly without good in silico models.
- 323 5y ago
  Why not just update the vaccine with the corresponding sequence from the Delta variant? Isn't the Delta variant today a better baseline than the ancestral virus? Or do a mix - first shot ancestral, second shot Delta.
  - nextos 5y ago
    I think this is the logical thing to do, but now there are two new roadblocks clinical trials have to face: * It's hard to recruit non-vaccinated participants * There will be safety issues to address on people that have received multiple shots and / or designed against different strains
    - dolni 5y ago
      What are the safety issues surrounding multiple shots or mixed vaccines?
- passivate 5y ago
  There are also approved vaccines based on the inactivated virus like Covaxin from India.
acconsta 5y ago
Moderna and Pfizer tested variant-specific (B1.351) boosters and found they weren't significantly more-effective than a third dose of the original vaccine. https://www.nature.com/articles/s41591-021-01527-y https://www.nature.com/articles/s41591-021-01527-y This may of course change with new variants.
- greg5green 5y ago
  >found they weren't more-effective than a third dose of the original vaccine This goes against the paper: >A boost with mRNA-1273.351 appeared to be more effective at neutralization of the B.1.351 virus than a boost with mRNA-1273, evidenced by the higher mean GMT levels in the Part C cohort 1 participants (1400) than the GMT Part B participants (864) against the B.1.351 virus. Additionally, the difference between the wild-type and B.1.351 assays at day 1 dropped from 7.7-fold prior to the boost with mRNA-1273.351 to 2.6-fold at 15 days after the boost. Thank you for posting this though -- I was looking for it earlier for my own comment and couldn't find it! Bookmarking now.
- greg5green 5y ago
  Looking at how this commentary has gone -- why do the worse comments gets get the most traffic? And those with actual data behind them -- zero?

by lol768 5y ago

angelzen 5y ago

That is a fantastic question. We are still vaccinating & boosting against the original variant. Would "the experts" please demonstrate that vaccines against variants are effective, given that original antigenic sin is a long known and well documented phenomenon? https://en.wikipedia.org/wiki/Original_antigenic_sin https://en.wikipedia.org/wiki/Original_antigenic_sin https://www.jstor.org/stable/985534 https://www.jstor.org/stable/985534

belltaco 5y ago
How is OAS related to ADE?
- angelzen 5y ago
  A South Korea paper from 2016 argues they are related "sometimes". Note that coronaviruses are RNA viruses. Now, all the epi data we have indicates that the covid mRNA vaccines are effective against covid variants of concern. No need to panic. "Original Antigenic Sin Response to RNA Viruses and Antiviral Immunity" "Abstract: The human immune system has evolved to fight against foreign pathogens. It plays a central role in the body's defense mechanism. However, the immune memory geared to fight off a previously recognized pathogen, tends to remember an original form of the pathogen when a variant form subsequently invades. This has been termed 'original antigenic sin'. This adverse immunological effect can alter vaccine effectiveness and sometimes cause enhanced pathogenicity or additional inflammatory responses, according to the type of pathogen and the circumstances of infection. Here we aim to give a simplified conceptual understanding of virus infection and original antigenic sin by comparing and contrasting the two examples of recurring infections such as influenza and dengue viruses in humans." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5086450 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5086450
blackbear_ 5y ago
> Would "the experts" please demonstrate that vaccines against variants are effective There's plenty of evidence that current vaccines work against variants: - https://www.cdc.gov/mmwr/volumes/70/wr/mm7034e4.htm https://www.cdc.gov/mmwr/volumes/70/wr/mm7034e4.htm - https://www.nejm.org/doi/full/10.1056/NEJMoa2108891 https://www.nejm.org/doi/full/10.1056/NEJMoa2108891 - https://www.cell.com/cell/fulltext/S0092-8674(21)01057-6#%20 https://www.cell.com/cell/fulltext/S0092-8674(21)01057-6#%20 > given that original antigenic sin is a long known and well documented phenomenon? This could apply both to vaccines and natural infections. Not sure what you are trying to say?
- MuffinFlavored 5y ago
  > There's plenty of evidence that current vaccines work against variants: Is there any reason to be afraid of getting vaccinated?
  - zzutz 5y ago
    besides the fact that plenty of European countries have banned the use of certain vaccines because of heart issues? besides the fact that Fauci is responsible for funding bio-terrorism in Wuhan? No not really.
  - didibus 5y ago
    > Is there any reason to be afraid of getting vaccinated? There's plenty of reasons, do you mean to also ask how likely other people on the internet believe each one to be? For example, if you ask me, this is my personal assessment: Reason 1 - Vaccines could also contain microchips or other device for tracking, brainwashing and remote manipulating my body and mind by whoever mastermind is in charge of what goes in them. I think that's very unlikely, I'd give it a 0.00000001% probability. I just dont know of any possibility for such advanced technology. And I can think of many different means that you can be more cost effectively tracked, manipulated or brain washed. I can also think of other ways they could have injected you with such things. Reason 2 - The vaccines will result in worst long terms negative effects on your health than getting Covid. I think this is a little more likely, but given all prior vaccines have shown to be quite safe, and even if they could be responsible for some long term effects, even some we haven't linked back to them yet, seeing as life expectancy and quality of life has grown year over year since the introduction of vaccines, it seems the equation would still play in their favor. There are also more and more literature linking prior viruses as a possible cause of long term negative effects like dimentia, various auto-immune diseases, etc. So it would seem Covid is more likely to introduce long term negative effects. So I'd give it a 1% chance. Reason 3 - The vaccines will result in worst short term effects on your health then getting Covid. I think this one has been shown that most of the time, Covid is more likely to kill you or make you really sick as compared to vaccines. I'd give this one a 0.0001% chance. Reason 4 - Vaccines can stop your pregnancy or your period and make you stink I have seen zero cases of this, and everyone who's had a vaccine to my nose do not smell, and still have period and can get pregnant. I'd give this one a 0.000000000000000001% chance. There might be more reasons, but those are the ones I've heard most often, and this is only my personal risk assessment.
greg5green 5y ago
They haven't found original antigenic sin so far. There's a couple links with some data (although I couldn't find a pre-print or published article right now) in this comment: https://news.ycombinator.com/item?id=29005187 https://news.ycombinator.com/item?id=29005187
- angelzen 5y ago
  Thanks for the links! Note that they are making variant-specific vaccines, not proving that variant-specific vaccines are effective against the target variant, if delivered after the original vaccine. Side note: I hope we can do better than taking at face value investor press releases by the biopharma corps producing the vaccines.
  - greg5green 5y ago
    >Note that they are making variant-specific vaccines, not proving that variant-specific vaccines are effective against the target variant, if delivered after the original vaccine. You are correct that it isn't proving vaccine efficacy, but it is showing a different set of antibodies created by the variant vaccines that are more effective at neutralizing the targeted variant than the antibody collection created by the original, WT-targeted vaccine. >Side note: I hope we can do better than taking at face value investor press releases by the biopharma corps producing the vaccines. I hate science by press release too. I wish I was better at bookmarking the pre-prints and journal articles I find/read, but they'd just be a mess I couldn't find anything in either :|
323 5y ago
OAS might be a problem with much more divergent future variants. Today's variant are still very close to the original, so OAS is not a factor yet.

greg5green 5y ago

I'm having trouble finding the paper, but I'm pretty I've seen a pre-print for mRNA-1273.351. This press release is the closest I could find on short notice: https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-positive-initial-booster-data-against-sars-cov https://investors.modernatx.com/news-releases/news-release-d... Novavax has also been working on a Beta variant booster (and I believe has moved on to a Delta booster that hasn't started NHP trials yet) -- here's some info from a presentation: https://www.novavax.com/sites/default/files/2021-05/NVAX-WVC2021-GregGlenn-FINAL.pdf https://www.novavax.com/sites/default/files/2021-05/NVAX-WVC... (It's slides 17 and 18) Pfizer/BioNTech definitely has a Delta booster getting ready for NHP trials, but my Google Fu is lacking today, apparently.

nextos 5y ago

I work at an immunology lab which is next door to most of the Oxford vaccine group. I think the quick (and overly simplistic) answer to this question is that models (e.g. convolutional networks) that predict which chunks of viral (or human) proteins are displayed to immune cells (HLA presentation), along with other kinds of models (like those predicting crossreactivity of T cell receptors against mutated epitopes) are really primitive (mostly because of low quality training datasets, it's not really a hard problem like e.g. protein folding). Hence, rushing a new vaccine is not easy as there is a lot of labwork to do. As a matter of fact, all COVID vaccine designs had essentially the same payload (the whole spike protein). Modern subunit vaccines would typically include only little chunks of the spike (to increase efficiency and avoid side effects). But this was not trivial to do quickly without good in silico models.

323 5y ago
Why not just update the vaccine with the corresponding sequence from the Delta variant? Isn't the Delta variant today a better baseline than the ancestral virus? Or do a mix - first shot ancestral, second shot Delta.
- nextos 5y ago
  I think this is the logical thing to do, but now there are two new roadblocks clinical trials have to face: * It's hard to recruit non-vaccinated participants * There will be safety issues to address on people that have received multiple shots and / or designed against different strains
  - dolni 5y ago
    What are the safety issues surrounding multiple shots or mixed vaccines?
passivate 5y ago
There are also approved vaccines based on the inactivated virus like Covaxin from India.

acconsta 5y ago

Moderna and Pfizer tested variant-specific (B1.351) boosters and found they weren't significantly more-effective than a third dose of the original vaccine. https://www.nature.com/articles/s41591-021-01527-y https://www.nature.com/articles/s41591-021-01527-y This may of course change with new variants.

greg5green 5y ago
>found they weren't more-effective than a third dose of the original vaccine This goes against the paper: >A boost with mRNA-1273.351 appeared to be more effective at neutralization of the B.1.351 virus than a boost with mRNA-1273, evidenced by the higher mean GMT levels in the Part C cohort 1 participants (1400) than the GMT Part B participants (864) against the B.1.351 virus. Additionally, the difference between the wild-type and B.1.351 assays at day 1 dropped from 7.7-fold prior to the boost with mRNA-1273.351 to 2.6-fold at 15 days after the boost. Thank you for posting this though -- I was looking for it earlier for my own comment and couldn't find it! Bookmarking now.
greg5green 5y ago
Looking at how this commentary has gone -- why do the worse comments gets get the most traffic? And those with actual data behind them -- zero?