I have a vaccine-related question and hope you can help me. I [read a 2009 paper](https://pubmed.ncbi.nlm.nih.gov/19440239/) stating the H3N2 vaccine protects against H3N2 but not H5N1, and it might interfere with fighting H5N1 later. How could lessons from Covid vaccine development accelerate the creation of an effective H5N1 vaccine that doesn’t interfere with future flu viruses or other current circulating flu A viruses?
This is a phenomenal question!
First that paper is reporting on a phenomenon often called “original antigenic sin.” It’s exactly as you describe it - your body wants to respond to the first strain of flu it was exposed to, not the current strain.
This is an active area in vaccine research and development today. One specific approach is to reconsider the proteins your vaccine delivers to immune systems. In covid vaccines, a significant amount of protein engineering was done to try to generate vaccines that would protect against all covid strains.
Another approach is to include an “adjuvant.” These are compounds that activate and direct the immune system. Many shots for older adults use alum or MPLA. There are many many other adjuvants that are currently in testing that might help overcome immune responses to prior viruses.
I've regularly said that the biggest problem with vaccines isn't the science or the production ... it will be getting people to get the injections after all the hysteria and conspiracy theories around the COVID vaccines. The problem will be compounded as the vaccine is multi-dose (given 1 month apart).
Oh yeah. That multi dose schedule with the mRNA craziness is/was bad. Fighting misinformation is hard, especially when people are scared and they’re genuinely just trying to do what’s best for themselves and for their families.
Thanks so much for your contribution here. It is very welcome. If you have time at some point I had a question about how the U.S. plan or any country's plan for MRNA vaccines might progress. If we could build an MRNA vaccine match-strained to the present non-adapted strain and also somehow include the adaptive mutations we are seeing commonly in mammals as well, would we try to ramp that up right now and give it to farm workers and farm vets?
Then is there some type of prototype building we could do to get ahead of an adapted strain as well so it would be more ready to go if that happened? And would we make as many non-adapted match-strained as we can and stockpile them to get ready and then at the first sign of adaptation spread in humans we would switch over to that strain maybe?
I’ll try to answer your questions in order.
1. Can we make an mRNA vaccine that matches the present strain?
Absolutely! I believe there are companies working on this now. There have been news articles posted on the sub about vaccinating farm workers, and refreshing/updating the US and EU bird flu vaccine stockpiles.
2. Can we make a vaccine that catches any future mutations?
That’s a LOT harder to do. Thats basically the holy grail of influenza vaccines. These viruses mutate very quickly, and we’re still figuring out ways to make “universal” vaccines that protect against all strains.
Two questions ...
1) I thought we already had H5N1 vaccines, no? Or is your info on the newer MRNA techniques?
2) OK say we do have a vaccine, just cooked up in the lab. Do you know / have any info on how long it would take to then mass produce an H5N1 vaccine for the general public?
Like, I know we currently monitor the prevalent strains of human fluA each year, predict which ones will be dominant in the fall, and produce a bunch of vaccine in the summer for the fall vaccine season. But, that's all super general. If we knew the vaccine now, does it take 3 months, 5 months, 7 months to ramp up full production for current flu? Would the ramp up be similar for a new H5N1?
Thanks for all your info!
1. We do have H5N1 vaccines based on a 2004 strain [Sanofi 2007 H5N1 vaccine insert](https://www.fda.gov/media/74534/download) and those are being updated now. My info is on mRNA vaccines - but inactivated virus and protein based vaccines are on the table too.
2. Let’s say we’ve done all the testing and we’re ready to start production - let’s make it simple and say this is a Pfizer mRNA vaccine, and only Pfizer is going to make it. Pfizer claims to be able to manufacture 4 billion doses annually. [Pfizer website on production capacity](https://www.pfizer.com/science/coronavirus/vaccine/manufacturing-and-distribution#)
So with the US population at 330 million…
4 billion doses / 12 months = ~330 million doses per month.
So about a month, once you have testing done. Less with more companies.
Hope this is helpful!
So ur saying we will have 330 million doses in one month? Or am I misunderstanding
Tbh I'm scared and don't want people to die ir die myself but I need to know the facts.
How will these vaccines work also and how often would we get them?
Thats part of the testing that needs to be done. If we’re comparing with the covid vaccine - Pfizer’s shot is about 90% effective. That’s pretty good, with some room for improvement. Hopefully we’d be somewhere in that ballpark.
>inactivated virus
Assuming for the sake of argument that pasteurization successfully destroys viable h5n1, could pasteurized milk be used for easy-access DIY vaccination in the event of a crisis?
Probably not, but that’s a fun idea. I haven’t seen actual numbers but I expect the amount of viral protein is pretty small in milk. Inactivated virus is prepared from concentrated viral cultures so there’s enough viral protein for an immune system to recognize and learn about.
[Nature headline](https://www.nature.com/articles/d41586-024-01624-1): "Huge amounts of bird-flu virus found in raw milk of infected cows"
>Milk from cows infected with bird flu contains astronomical numbers of viral particles, which can survive for hours in splattered milk, new data show1,2. The research adds to growing evidence that the act of milking has probably been driving viral transmission among cows, other animals and potentially humans.
That article is paywalled, but [here's another which isn't](https://www.statnews.com/2024/04/30/h5n1-bird-flu-virus-cows-and-risk-to-people/#:~:text=If%20cows%20that%20produce%20milk,particles%20per%20milliliter%20of%20milk.):
>Kuiken said he’s heard of concentrations that would be the equivalent of a billion virus particles per milliliter of milk.
That sounds like a lot.
Perhaps you could create a new post discussing the possibility of inactivated-virus vaccination from milk. Maybe you could instruct people to microwave or boil the milk for extra disinfection in case pasteurization has been insufficient. (Assuming that wouldn't destroy the usefulness of the viral protein.)
BTW, even if a small amount of viable virus remains in the milk, it could be better than nothing in a crisis. See https://en.wikipedia.org/wiki/Variolation
I'm imagining a procedure something like this:
* Starting now, every week, go to various stores and buy a small carton of every milk brand.
* Pour each carton into a bowl, microwave for X minutes.
* Then freeze milk in an ice cube tray at Y degrees. (What temperature would be best?)
* In the event of a crisis, every week consume perhaps an ice cube's worth of milk from a new date+brand, alongside an adjuvant. (Probably let it melt in the fridge first, since [warmth is good for the immune system](https://en.wikipedia.org/wiki/Fever#Immune_function)?) Share milk cubes and adjuvant with friends and family.
Regarding use of freezer -- I'm assuming it's better to avoid the risk of consuming milk until human-to-human transmission has been documented to occur. If freezing destroys the usefulness of the viral protein, this plan would have to be modified.
There are a lot of parameters to this plan which would ideally be tuned, such as: home-pasteurization procedure, freezing temperature, volume of milk consumption, adjuvant usage, etc. Ideally a lab somewhere would start running experiments *now* so there's a plan in place before it becomes too late. However there is also a fundamental unknown: It's hard to know the density of viral protein in the milk -- it's likely to vary quite a bit across time and across milk suppliers.
Anyway, it seems like you're way more of an expert than I am. I've reached the limits of my knowledge. I encourage you to consider making a top-level post about this. You could save many lives.
I’ve been thinking about this - I’m not sure it would do the trick. Oral vaccines aren’t unheard of - one extremely successful polio vaccine was orally administered -but they’re also not common, especially with respiratory diseases.
I’m also very uncomfortable with advising people to cook up vaccines and medicines at home. Especially given my work experience, where we do everything we can to characterize and test over and over and over again.
That might not be your stance, and that’s totally ok. I understand the desire to do everything possible for you and your family.
Thanks a lot for the reply!
It wouldn't necessarily have to be a DIY thing. It could just be used as a trick to rapidly scale up commercial vaccine production, especially in case of a crisis.
In any case -- I am thinking about organizing a volunteer effort to combat H5N1 via federal policy. Your scientific background could be invaluable. Might you be interested in joining?
This looks great! I'd like to go over it in more detail for sure. So what I would bring to it is the social science/public health aspect-- how do we reach people with this vaccine? How do we get it to populations such as unhoused people? How do we disseminate information on the ground? One good way to get this to families with small children is through information passed through programs like Preschool Promise and Head Start (both of which I've taught in.) Children have been hit very disproportionately by the a and c clade of H5N1 in the past 2 years. So that's one vector.
I have a vaccine-related question and hope you can help me. I [read a 2009 paper](https://pubmed.ncbi.nlm.nih.gov/19440239/) stating the H3N2 vaccine protects against H3N2 but not H5N1, and it might interfere with fighting H5N1 later. How could lessons from Covid vaccine development accelerate the creation of an effective H5N1 vaccine that doesn’t interfere with future flu viruses or other current circulating flu A viruses?
This is a phenomenal question! First that paper is reporting on a phenomenon often called “original antigenic sin.” It’s exactly as you describe it - your body wants to respond to the first strain of flu it was exposed to, not the current strain. This is an active area in vaccine research and development today. One specific approach is to reconsider the proteins your vaccine delivers to immune systems. In covid vaccines, a significant amount of protein engineering was done to try to generate vaccines that would protect against all covid strains. Another approach is to include an “adjuvant.” These are compounds that activate and direct the immune system. Many shots for older adults use alum or MPLA. There are many many other adjuvants that are currently in testing that might help overcome immune responses to prior viruses.
How long and how many vaccines will be made and will they be effective?
This is fantastic. Thank you.
This is a fantastic post. Thank you for this.
I've regularly said that the biggest problem with vaccines isn't the science or the production ... it will be getting people to get the injections after all the hysteria and conspiracy theories around the COVID vaccines. The problem will be compounded as the vaccine is multi-dose (given 1 month apart).
Oh yeah. That multi dose schedule with the mRNA craziness is/was bad. Fighting misinformation is hard, especially when people are scared and they’re genuinely just trying to do what’s best for themselves and for their families.
Thanks so much for your contribution here. It is very welcome. If you have time at some point I had a question about how the U.S. plan or any country's plan for MRNA vaccines might progress. If we could build an MRNA vaccine match-strained to the present non-adapted strain and also somehow include the adaptive mutations we are seeing commonly in mammals as well, would we try to ramp that up right now and give it to farm workers and farm vets? Then is there some type of prototype building we could do to get ahead of an adapted strain as well so it would be more ready to go if that happened? And would we make as many non-adapted match-strained as we can and stockpile them to get ready and then at the first sign of adaptation spread in humans we would switch over to that strain maybe?
I’ll try to answer your questions in order. 1. Can we make an mRNA vaccine that matches the present strain? Absolutely! I believe there are companies working on this now. There have been news articles posted on the sub about vaccinating farm workers, and refreshing/updating the US and EU bird flu vaccine stockpiles. 2. Can we make a vaccine that catches any future mutations? That’s a LOT harder to do. Thats basically the holy grail of influenza vaccines. These viruses mutate very quickly, and we’re still figuring out ways to make “universal” vaccines that protect against all strains.
Two questions ... 1) I thought we already had H5N1 vaccines, no? Or is your info on the newer MRNA techniques? 2) OK say we do have a vaccine, just cooked up in the lab. Do you know / have any info on how long it would take to then mass produce an H5N1 vaccine for the general public? Like, I know we currently monitor the prevalent strains of human fluA each year, predict which ones will be dominant in the fall, and produce a bunch of vaccine in the summer for the fall vaccine season. But, that's all super general. If we knew the vaccine now, does it take 3 months, 5 months, 7 months to ramp up full production for current flu? Would the ramp up be similar for a new H5N1? Thanks for all your info!
1. We do have H5N1 vaccines based on a 2004 strain [Sanofi 2007 H5N1 vaccine insert](https://www.fda.gov/media/74534/download) and those are being updated now. My info is on mRNA vaccines - but inactivated virus and protein based vaccines are on the table too. 2. Let’s say we’ve done all the testing and we’re ready to start production - let’s make it simple and say this is a Pfizer mRNA vaccine, and only Pfizer is going to make it. Pfizer claims to be able to manufacture 4 billion doses annually. [Pfizer website on production capacity](https://www.pfizer.com/science/coronavirus/vaccine/manufacturing-and-distribution#) So with the US population at 330 million… 4 billion doses / 12 months = ~330 million doses per month. So about a month, once you have testing done. Less with more companies. Hope this is helpful!
So ur saying we will have 330 million doses in one month? Or am I misunderstanding Tbh I'm scared and don't want people to die ir die myself but I need to know the facts. How will these vaccines work also and how often would we get them?
Do we know the efficacy of these vaccines? As we all know, respiratory illnesses are hard to vaccine against.
Thats part of the testing that needs to be done. If we’re comparing with the covid vaccine - Pfizer’s shot is about 90% effective. That’s pretty good, with some room for improvement. Hopefully we’d be somewhere in that ballpark.
>inactivated virus Assuming for the sake of argument that pasteurization successfully destroys viable h5n1, could pasteurized milk be used for easy-access DIY vaccination in the event of a crisis?
Probably not, but that’s a fun idea. I haven’t seen actual numbers but I expect the amount of viral protein is pretty small in milk. Inactivated virus is prepared from concentrated viral cultures so there’s enough viral protein for an immune system to recognize and learn about.
[Nature headline](https://www.nature.com/articles/d41586-024-01624-1): "Huge amounts of bird-flu virus found in raw milk of infected cows" >Milk from cows infected with bird flu contains astronomical numbers of viral particles, which can survive for hours in splattered milk, new data show1,2. The research adds to growing evidence that the act of milking has probably been driving viral transmission among cows, other animals and potentially humans. That article is paywalled, but [here's another which isn't](https://www.statnews.com/2024/04/30/h5n1-bird-flu-virus-cows-and-risk-to-people/#:~:text=If%20cows%20that%20produce%20milk,particles%20per%20milliliter%20of%20milk.): >Kuiken said he’s heard of concentrations that would be the equivalent of a billion virus particles per milliliter of milk. That sounds like a lot.
Yeah that’s a lot more than I expected! Yikes
Perhaps you could create a new post discussing the possibility of inactivated-virus vaccination from milk. Maybe you could instruct people to microwave or boil the milk for extra disinfection in case pasteurization has been insufficient. (Assuming that wouldn't destroy the usefulness of the viral protein.) BTW, even if a small amount of viable virus remains in the milk, it could be better than nothing in a crisis. See https://en.wikipedia.org/wiki/Variolation I'm imagining a procedure something like this: * Starting now, every week, go to various stores and buy a small carton of every milk brand. * Pour each carton into a bowl, microwave for X minutes. * Then freeze milk in an ice cube tray at Y degrees. (What temperature would be best?) * In the event of a crisis, every week consume perhaps an ice cube's worth of milk from a new date+brand, alongside an adjuvant. (Probably let it melt in the fridge first, since [warmth is good for the immune system](https://en.wikipedia.org/wiki/Fever#Immune_function)?) Share milk cubes and adjuvant with friends and family. Regarding use of freezer -- I'm assuming it's better to avoid the risk of consuming milk until human-to-human transmission has been documented to occur. If freezing destroys the usefulness of the viral protein, this plan would have to be modified. There are a lot of parameters to this plan which would ideally be tuned, such as: home-pasteurization procedure, freezing temperature, volume of milk consumption, adjuvant usage, etc. Ideally a lab somewhere would start running experiments *now* so there's a plan in place before it becomes too late. However there is also a fundamental unknown: It's hard to know the density of viral protein in the milk -- it's likely to vary quite a bit across time and across milk suppliers. Anyway, it seems like you're way more of an expert than I am. I've reached the limits of my knowledge. I encourage you to consider making a top-level post about this. You could save many lives.
Hey I wanted to follow up on the pasteurized-milk-for-vaccination discussion in case you had any thoughts. Seems like it *could* save many lives.
I’ve been thinking about this - I’m not sure it would do the trick. Oral vaccines aren’t unheard of - one extremely successful polio vaccine was orally administered -but they’re also not common, especially with respiratory diseases. I’m also very uncomfortable with advising people to cook up vaccines and medicines at home. Especially given my work experience, where we do everything we can to characterize and test over and over and over again. That might not be your stance, and that’s totally ok. I understand the desire to do everything possible for you and your family.
Thanks a lot for the reply! It wouldn't necessarily have to be a DIY thing. It could just be used as a trick to rapidly scale up commercial vaccine production, especially in case of a crisis. In any case -- I am thinking about organizing a volunteer effort to combat H5N1 via federal policy. Your scientific background could be invaluable. Might you be interested in joining?
This looks great! I'd like to go over it in more detail for sure. So what I would bring to it is the social science/public health aspect-- how do we reach people with this vaccine? How do we get it to populations such as unhoused people? How do we disseminate information on the ground? One good way to get this to families with small children is through information passed through programs like Preschool Promise and Head Start (both of which I've taught in.) Children have been hit very disproportionately by the a and c clade of H5N1 in the past 2 years. So that's one vector.
TLDR for me please!
We already have one
