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Plus a flu vaccine: > mRNA vaccines [...] generate a much stronger immune response than responses that are generated to the protein in a normal flu vaccine [..

by est31 6y ago

Plus a flu vaccine: > mRNA vaccines [...] generate a much stronger immune response than responses that are generated to the protein in a normal flu vaccine [...] > One limitation of the current flu vaccines is that they take about six months to develop, meaning scientists must choose which strains they think will be prevalent in the next flu season — even before the current one is over. So by the time the vaccines are ready for distribution, a different strain may have emerged as the better target. > An mRNA flu vaccine, on the other hand, can be developed in about a month or so, giving researchers much more time to determine which strains to protect against. https://www.washingtonpost.com/health/2021/04/11/mrna-flu-shots/ https://www.washingtonpost.com/health/2021/04/11/mrna-flu-sh... The flu vaccine seems to me to have a better chance of working than an HIV vaccine because we have been trying for decades to come up with one for HIV, without any success at all. I'm not saying that their attempts won't work either, but it's more of a bet than a flu vaccine. An iterative improvement on the existing flu vaccines would still be very helpful.

lisper 6y ago
> by the time the vaccines are ready for distribution, a different strain may have emerged as the better target I have never understood this. How many strains are there? I thought there were only like 4 or so. Why don't they just do them all every year?
- cannaceo 6y ago
  There are subtypes of each. Influenza A and B cause the seasonal flu. The subtypes are named by their hemagglutinin (H) and neuraminidase (N). E.g. H1N1, H5N9, etc.
  - lisper 6y ago
    OK, but that doesn't really answer my question. Turns out the answer can be found here: https://www.cdc.gov/flu/about/viruses/types.htm https://www.cdc.gov/flu/about/viruses/types.htm "There are four types of influenza viruses: A, B, C and D. Human influenza A and B viruses cause seasonal epidemics of disease (known as the flu season) almost every winter in the United States. Influenza A viruses are the only influenza viruses known to cause flu pandemics, i.e., global epidemics of flu disease. A pandemic can occur when a new and very different influenza A virus emerges that both infects people and has the ability to spread efficiently between people. Influenza type C infections generally cause mild illness and are not thought to cause human flu epidemics. Influenza D viruses primarily affect cattle and are not known to infect or cause illness in people." "Influenza A viruses are divided into subtypes based on two proteins on the surface of the virus: hemagglutinin (H) and neuraminidase (N). There are 18 different hemagglutinin subtypes and 11 different neuraminidase subtypes (H1 through H18 and N1 through N11, respectively). While there are potentially 198 different influenza A subtype combinations, only 131 subtypes have been detected in nature. Current subtypes of influenza A viruses that routinely circulate in people include: A(H1N1) and A(H3N2). Influenza A subtypes can be further broken down into different genetic “clades” and “sub-clades.” See the “Influenza Viruses” graphic below for a visual depiction of these classifications." So the answer is: 198 possible strains, 131 that actually occur. That explains why they have to pick and choose.
    - elcritch 6y ago
      It seems they could pre-make vaccines for all 131 extant types and then mix the flu shots based on the current season. Though, likely that wouldn’t be economical. It does raise the question of why they couldn’t just put a bit of all 131 subtypes in the vaccine. Or if that’d overload the immune system, say, the X subtypes most likely to makeup say 99% of probable flu season strains.
      - lazide 6y ago
        They could - but up until recently no one cared enough, both for R&D spend and to get or mandate enough shots for it to work at it’s stated goals. We’ve had people even recently refusing to give their kids polio, tetanus, or measles vaccines - and even 5 minutes of honest research or questions to a doctor will make quite clear how bad an idea THAT is. Getting 100+ flu vaccines, all which would have to go through a pipeline taking nearly a decade, when ‘nothing bad has happened’ on that topic for a hundred years? Ain’t nobody going to pay for that. We’ll see how the calculus is different soon. I for one would rather my tax dollars go towards figuring something like never having the flu again than blowing up some random middle eastern country a couple more times.
        jbjbjbjb 6y ago
        There’s got to be a large market for that given the entire elderly population is offered a flu shot every year. Doing that as a one off would be a huge cost saving.
        lazide 6y ago
        Not sure it would pay for itself even in 100 years if you use that metric. $20 (likely current retail cost of a flu shot) x the 46 million older adults in the US is a hair less than a billion a year. Making 131 or so effective flu vaccines and getting them through the process with the prior known and effective process? (including all the failed attempts) Hopefully we’d get some economies of scale, estimates [https://www.passporthealthusa.com/2018/02/how-much-does-it-cost-to-develop-a-new-vaccine/ https://www.passporthealthusa.com/2018/02/how-much-does-it-c...] I found had it between 500m to 2.5billion and a decade each. So 65billion to 327billion. So between 65 to 327 years for positive ROI if that was your metric. If you’re talking public good, it would be immeasurable for us and the world though, no question, and on the high end that’s less than a third [https://www.google.com/amp/s/www.bbc.co.uk/news/world-47391821.amp https://www.google.com/amp/s/www.bbc.co.uk/news/world-473918...] of what we’ve spent in Afghanistan alone.
  - amluto 6y ago
    And those subtypes themselves are constantly mutating. Look at actual WHO vaccine recommendations: https://www.who.int/influenza/vaccines/virus/recommendations/2021-22_north/en/ https://www.who.int/influenza/vaccines/virus/recommendations...
- azinman2 6y ago
  They constantly mutate.
vmception 6y ago
It seems like with HIV they can simply sequence the prevalent evolutionary outcome in your body within a month and give your body the blueprint to destroy that version What typically happens with HIV is that the body kills most of it initially, but the remaining ones keep rapidly evolving until an iteration evades your immune response, this takes about 12 years. Seems like an mRNA vaccine could be done every 3 years for individuals and either completely eradicate the HIV presence in the body or do it once every 12 years for a reset Let me know if I fundamentally misunderstand something
- robbiep 6y ago
  That's not quite true - HIV of course mutates but in-patient mutations are generally considered to have a negligible effect on outcomes/have a negligible effect as a driver of morbidity . What is the big driver of HIV is in the name, it's a Immunodeficiency virus - it kills CD4+ T cells and other cells of the immune system. At a certain point you don't have enough CD4+ T cells left and you lose your adaptive/cell-mediated immune system and then you're in big trouble. Essentially it's a war of attrition and unless you're part of some tiny proportion of people who have either a form of immunity against it or an immune system that for whatever reason is able to continue waging war on it then you will succumb
stefantalpalaru 6y ago
> mRNA vaccines [...] generate a much stronger immune response than responses that are generated to the protein in a normal flu vaccine [...] That's probably due to the immunogenicity of those lipid nanoparticles used to encapsulate the mRNA (particularly the cationic lipid): https://www.biorxiv.org/content/10.1101/2021.03.04.430128v1.full https://www.biorxiv.org/content/10.1101/2021.03.04.430128v1....
lobocinza 6y ago
VaC (Vaccine as Code)

by est31 6y ago

lisper 6y ago

> by the time the vaccines are ready for distribution, a different strain may have emerged as the better target I have never understood this. How many strains are there? I thought there were only like 4 or so. Why don't they just do them all every year?

cannaceo 6y ago
There are subtypes of each. Influenza A and B cause the seasonal flu. The subtypes are named by their hemagglutinin (H) and neuraminidase (N). E.g. H1N1, H5N9, etc.
- lisper 6y ago
  OK, but that doesn't really answer my question. Turns out the answer can be found here: https://www.cdc.gov/flu/about/viruses/types.htm https://www.cdc.gov/flu/about/viruses/types.htm "There are four types of influenza viruses: A, B, C and D. Human influenza A and B viruses cause seasonal epidemics of disease (known as the flu season) almost every winter in the United States. Influenza A viruses are the only influenza viruses known to cause flu pandemics, i.e., global epidemics of flu disease. A pandemic can occur when a new and very different influenza A virus emerges that both infects people and has the ability to spread efficiently between people. Influenza type C infections generally cause mild illness and are not thought to cause human flu epidemics. Influenza D viruses primarily affect cattle and are not known to infect or cause illness in people." "Influenza A viruses are divided into subtypes based on two proteins on the surface of the virus: hemagglutinin (H) and neuraminidase (N). There are 18 different hemagglutinin subtypes and 11 different neuraminidase subtypes (H1 through H18 and N1 through N11, respectively). While there are potentially 198 different influenza A subtype combinations, only 131 subtypes have been detected in nature. Current subtypes of influenza A viruses that routinely circulate in people include: A(H1N1) and A(H3N2). Influenza A subtypes can be further broken down into different genetic “clades” and “sub-clades.” See the “Influenza Viruses” graphic below for a visual depiction of these classifications." So the answer is: 198 possible strains, 131 that actually occur. That explains why they have to pick and choose.
  - elcritch 6y ago
    It seems they could pre-make vaccines for all 131 extant types and then mix the flu shots based on the current season. Though, likely that wouldn’t be economical. It does raise the question of why they couldn’t just put a bit of all 131 subtypes in the vaccine. Or if that’d overload the immune system, say, the X subtypes most likely to makeup say 99% of probable flu season strains.
    - lazide 6y ago
      They could - but up until recently no one cared enough, both for R&D spend and to get or mandate enough shots for it to work at it’s stated goals. We’ve had people even recently refusing to give their kids polio, tetanus, or measles vaccines - and even 5 minutes of honest research or questions to a doctor will make quite clear how bad an idea THAT is. Getting 100+ flu vaccines, all which would have to go through a pipeline taking nearly a decade, when ‘nothing bad has happened’ on that topic for a hundred years? Ain’t nobody going to pay for that. We’ll see how the calculus is different soon. I for one would rather my tax dollars go towards figuring something like never having the flu again than blowing up some random middle eastern country a couple more times.
      - jbjbjbjb 6y ago
        There’s got to be a large market for that given the entire elderly population is offered a flu shot every year. Doing that as a one off would be a huge cost saving.
        lazide 6y ago
        Not sure it would pay for itself even in 100 years if you use that metric. $20 (likely current retail cost of a flu shot) x the 46 million older adults in the US is a hair less than a billion a year. Making 131 or so effective flu vaccines and getting them through the process with the prior known and effective process? (including all the failed attempts) Hopefully we’d get some economies of scale, estimates [https://www.passporthealthusa.com/2018/02/how-much-does-it-cost-to-develop-a-new-vaccine/ https://www.passporthealthusa.com/2018/02/how-much-does-it-c...] I found had it between 500m to 2.5billion and a decade each. So 65billion to 327billion. So between 65 to 327 years for positive ROI if that was your metric. If you’re talking public good, it would be immeasurable for us and the world though, no question, and on the high end that’s less than a third [https://www.google.com/amp/s/www.bbc.co.uk/news/world-47391821.amp https://www.google.com/amp/s/www.bbc.co.uk/news/world-473918...] of what we’ve spent in Afghanistan alone.
- amluto 6y ago
  And those subtypes themselves are constantly mutating. Look at actual WHO vaccine recommendations: https://www.who.int/influenza/vaccines/virus/recommendations/2021-22_north/en/ https://www.who.int/influenza/vaccines/virus/recommendations...
azinman2 6y ago
They constantly mutate.

vmception 6y ago

It seems like with HIV they can simply sequence the prevalent evolutionary outcome in your body within a month and give your body the blueprint to destroy that version What typically happens with HIV is that the body kills most of it initially, but the remaining ones keep rapidly evolving until an iteration evades your immune response, this takes about 12 years. Seems like an mRNA vaccine could be done every 3 years for individuals and either completely eradicate the HIV presence in the body or do it once every 12 years for a reset Let me know if I fundamentally misunderstand something

robbiep 6y ago
That's not quite true - HIV of course mutates but in-patient mutations are generally considered to have a negligible effect on outcomes/have a negligible effect as a driver of morbidity . What is the big driver of HIV is in the name, it's a Immunodeficiency virus - it kills CD4+ T cells and other cells of the immune system. At a certain point you don't have enough CD4+ T cells left and you lose your adaptive/cell-mediated immune system and then you're in big trouble. Essentially it's a war of attrition and unless you're part of some tiny proportion of people who have either a form of immunity against it or an immune system that for whatever reason is able to continue waging war on it then you will succumb

stefantalpalaru 6y ago

> mRNA vaccines [...] generate a much stronger immune response than responses that are generated to the protein in a normal flu vaccine [...] That's probably due to the immunogenicity of those lipid nanoparticles used to encapsulate the mRNA (particularly the cationic lipid): https://www.biorxiv.org/content/10.1101/2021.03.04.430128v1.full https://www.biorxiv.org/content/10.1101/2021.03.04.430128v1....

lobocinza 6y ago

VaC (Vaccine as Code)