New mRNA vaccine for Malaria
July 23, 2023 3:37 PM Subscribe
It stops it in the liver after the infection sets in there. That new mRNA vaccines they developed in the COVID days has now been tweaked to do Malaria.
It's still early.
Australian scientists developed an mRNA-based vaccine that effectively stimulates protective immune cell responses against the malaria-causing parasite Plasmodium in preclinical models. It relies on T-cells that halts malaria infection in the liver to completely stop the spread of infection. (nature.com)
Mod note: Extra link has been removed!
posted by travelingthyme (staff) at 3:57 PM on July 23, 2023 [1 favorite]
posted by travelingthyme (staff) at 3:57 PM on July 23, 2023 [1 favorite]
An effective malaria vaccine would be a game changer for the world's population.
The mRNA technology could be a game changer for human health in a lot of ways.
I really hope it lives up to its promise.
posted by hippybear at 4:00 PM on July 23, 2023 [9 favorites]
The mRNA technology could be a game changer for human health in a lot of ways.
I really hope it lives up to its promise.
posted by hippybear at 4:00 PM on July 23, 2023 [9 favorites]
This is really excellent - such a brutal disease in parts of the world, for all all ages. I hope it's made easily accessible and affordable.
posted by coffeecat at 4:09 PM on July 23, 2023 [1 favorite]
posted by coffeecat at 4:09 PM on July 23, 2023 [1 favorite]
I just hope mRNA tech lives up to (at least) *part* of its promise(s). They promise a lot. I do think we're just starting to crack the world of gene to biology. Unless there's some low hanging fruit I'll probably be dead before it really gets going.
posted by aleph at 4:10 PM on July 23, 2023
posted by aleph at 4:10 PM on July 23, 2023
Timely, as the disease may be returning to the global north.
posted by Big Al 8000 at 4:12 PM on July 23, 2023 [1 favorite]
posted by Big Al 8000 at 4:12 PM on July 23, 2023 [1 favorite]
I hope this turns out to work as well as hoped.
posted by Dip Flash at 4:14 PM on July 23, 2023 [1 favorite]
posted by Dip Flash at 4:14 PM on July 23, 2023 [1 favorite]
I also hope this works as well as we think it might. If it does, it could alleviate suffering for hundreds of millions, and prevent hundreds of thousands of deaths each year.
posted by mollweide at 6:25 PM on July 23, 2023 [2 favorites]
posted by mollweide at 6:25 PM on July 23, 2023 [2 favorites]
As much as I'm interested in it working, I'm more interested in wether it will be cost prohibitive, we are, after all, discussing the pharmaceutical industry, noted friends to all mankind.
posted by evilDoug at 9:01 PM on July 23, 2023 [3 favorites]
posted by evilDoug at 9:01 PM on July 23, 2023 [3 favorites]
This is in mice, AFAICT. Long haul ahead. Not clear to me if there is a reason to expect this to be superior to the existing vaccine. AFAICT it is at least a fundamentally different target, which gives it a shot of being effective.
Regardless, more options and ongoing research are always good though.
As much as I'm interested in it working, I'm more interested in wether it will be cost prohibitive, we are, after all, discussing the pharmaceutical industry, noted friends to all mankind.
Vaccines, unlike the drugs I work on, don't have exceedingly high profit margins: They have decent mark ups but high volume. The Covid mRNA vaccine seems to cost about $20 / dose when the US government buys it. That's should be a reasonable upper estimate for the cost of government funded distribution of an mRNA mass vaccine.
So if this works, and the world wants to pay that much, it won't be cost prohibitive. It's certainly possible for wealthy countries to pay and distribute it across Africa; the aggregate cost of doses for everyone is less than the Pentagon budget by an order of magnitude.
posted by mark k at 12:10 AM on July 24, 2023 [5 favorites]
Regardless, more options and ongoing research are always good though.
As much as I'm interested in it working, I'm more interested in wether it will be cost prohibitive, we are, after all, discussing the pharmaceutical industry, noted friends to all mankind.
Vaccines, unlike the drugs I work on, don't have exceedingly high profit margins: They have decent mark ups but high volume. The Covid mRNA vaccine seems to cost about $20 / dose when the US government buys it. That's should be a reasonable upper estimate for the cost of government funded distribution of an mRNA mass vaccine.
So if this works, and the world wants to pay that much, it won't be cost prohibitive. It's certainly possible for wealthy countries to pay and distribute it across Africa; the aggregate cost of doses for everyone is less than the Pentagon budget by an order of magnitude.
posted by mark k at 12:10 AM on July 24, 2023 [5 favorites]
I don't know anyone who's ever had malaria. Do you? The countries affected are poor. I'm cynical enough to believe this is why there isn't a malaria vaccine already, the potential customers are broke.
They have to sell it cheap for the same reason. The customers are broke.
My concern with cost prohibition is the research into an mrna vaccine for cancer. A vaccine for cancer! Give yourself a moment to stop and think - what would a world without cancer be like? It's within reach, the early results are looking good. Really good.
But, because of the way it works, the mrna vaccine has to be custom made for the individual and their particular cancer.
Now you can see how we end up in a world without cancer for rich people.
posted by adept256 at 12:36 AM on July 24, 2023 [1 favorite]
They have to sell it cheap for the same reason. The customers are broke.
My concern with cost prohibition is the research into an mrna vaccine for cancer. A vaccine for cancer! Give yourself a moment to stop and think - what would a world without cancer be like? It's within reach, the early results are looking good. Really good.
But, because of the way it works, the mrna vaccine has to be custom made for the individual and their particular cancer.
Now you can see how we end up in a world without cancer for rich people.
posted by adept256 at 12:36 AM on July 24, 2023 [1 favorite]
adept256: I don't know anyone who's ever had malaria. Do you?
Yes, I've had malaria. I caught it in Chad. That means your point stands.
But at least I can tell you a bit about how it felt. It felt like a really bad, horrendous hangover that went away overnight and then came back every day around noon, to stick around for the rest of the day, making me completely unable to do anything at all. It was extremely unpleasant. Headache, fever, aching joints. It hurt to move my eyeballs.
And that was a weakened attack because I had used Lariam as a prophylaxe.
This new potential vaccine sounds quite promising and I hope it grows legs.
posted by Too-Ticky at 3:03 AM on July 24, 2023 [7 favorites]
Yes, I've had malaria. I caught it in Chad. That means your point stands.
But at least I can tell you a bit about how it felt. It felt like a really bad, horrendous hangover that went away overnight and then came back every day around noon, to stick around for the rest of the day, making me completely unable to do anything at all. It was extremely unpleasant. Headache, fever, aching joints. It hurt to move my eyeballs.
And that was a weakened attack because I had used Lariam as a prophylaxe.
This new potential vaccine sounds quite promising and I hope it grows legs.
posted by Too-Ticky at 3:03 AM on July 24, 2023 [7 favorites]
We can't really say, because the vaccine doesn't exist yet, but generally vaccines are one of the best values in healthcare. Even if you had to take a malaria vaccine regularly, or if it only reduced the severity of the disease, the economic benefits of not being sick could easily outweigh the cost of the vaccine, even in poor countries.
I also wonder if part of the challenge in creating a malaria vaccine is because it is a plasmodium. I was expecting maybe zika, dengue or chikungunya vaccines before malaria since those are all viral. A multivalent vaccine against all the tropical fevers in an area would be amazing.
posted by snofoam at 5:19 AM on July 24, 2023 [2 favorites]
I also wonder if part of the challenge in creating a malaria vaccine is because it is a plasmodium. I was expecting maybe zika, dengue or chikungunya vaccines before malaria since those are all viral. A multivalent vaccine against all the tropical fevers in an area would be amazing.
posted by snofoam at 5:19 AM on July 24, 2023 [2 favorites]
I too have had malaria, with a fever so high I couldn’t walk.
Sure local gouvernements may not “afford” it but I can’t imagine mass vaccination campaigns for it would be any more expensive than the aid money that’s spent on bed net distributions, paying community health workers, maintaining medicine supply stocks, and treatment of severe malaria.
posted by raccoon409 at 5:53 AM on July 24, 2023 [4 favorites]
Sure local gouvernements may not “afford” it but I can’t imagine mass vaccination campaigns for it would be any more expensive than the aid money that’s spent on bed net distributions, paying community health workers, maintaining medicine supply stocks, and treatment of severe malaria.
posted by raccoon409 at 5:53 AM on July 24, 2023 [4 favorites]
Headache, fever, aching joints. It hurt to move my eyeballs.
And that was a weakened attack because I had used Lariam as a prophylaxe.
I was lucky enough to not catch malaria, but personally I loved the lariam/mefloquine dreams. Best medication side effect I've ever had, though I know a lot of people have much less pleasant experiences.
posted by Dip Flash at 7:05 AM on July 24, 2023
And that was a weakened attack because I had used Lariam as a prophylaxe.
I was lucky enough to not catch malaria, but personally I loved the lariam/mefloquine dreams. Best medication side effect I've ever had, though I know a lot of people have much less pleasant experiences.
posted by Dip Flash at 7:05 AM on July 24, 2023
@aleph:
> I just hope mRNA tech lives up to (at least) *part* of its promise(s).
Where have you been for the last 3 years? I can't even.
@adept256 :
> I'm cynical enough to believe this is why there isn't a malaria vaccine already, the potential customers are broke.
You're ignorant. This is not quite as wrong as complaining that nobody has discovered an antibiotic that treats the common cold, but not by much. As a remedy, consider taking a few minutes to review some of the things that have been tried, and why they did not work.
posted by Aardvark Cheeselog at 7:06 AM on July 24, 2023 [3 favorites]
> I just hope mRNA tech lives up to (at least) *part* of its promise(s).
Where have you been for the last 3 years? I can't even.
@adept256 :
> I'm cynical enough to believe this is why there isn't a malaria vaccine already, the potential customers are broke.
You're ignorant. This is not quite as wrong as complaining that nobody has discovered an antibiotic that treats the common cold, but not by much. As a remedy, consider taking a few minutes to review some of the things that have been tried, and why they did not work.
posted by Aardvark Cheeselog at 7:06 AM on July 24, 2023 [3 favorites]
Not clear to me if there is a reason to expect this to be superior to the existing vaccine.
One specific detail that stood out to me in the paper is that prior infection with malaria can suppress the efficacy of existing vaccines by reducing the development of immune memory cells in the liver somehow. As a result, practical efficacy in regions with endemic malaria is generally lower than in trials. Apparently this mRNA vaccine does not suffer from the same problem (in mice).
There are a couple other advantages mentioned, but they're a bit too technical for me to parse (I am not an expert in immunology or any closely related field, just a person from another scientific field who is used to reading journal articles.)
posted by egregious theorem at 7:35 AM on July 24, 2023 [1 favorite]
One specific detail that stood out to me in the paper is that prior infection with malaria can suppress the efficacy of existing vaccines by reducing the development of immune memory cells in the liver somehow. As a result, practical efficacy in regions with endemic malaria is generally lower than in trials. Apparently this mRNA vaccine does not suffer from the same problem (in mice).
There are a couple other advantages mentioned, but they're a bit too technical for me to parse (I am not an expert in immunology or any closely related field, just a person from another scientific field who is used to reading journal articles.)
posted by egregious theorem at 7:35 AM on July 24, 2023 [1 favorite]
> I'm cynical enough to believe this is why there isn't a malaria vaccine already, the potential customers are broke.
There have been many efforts, over decades, to develop a vaccine. There is a lot of motivation to do so because malarial disease is holding back economic development in the regions where it is prevalent. But it’s a tough nut to crack because, for one thing, there are 4 different species of the malarial parasite that can infect humans and they each look different to the immune system. Even worse is that the parasite goes through many different life cycle stages in the human body, and at every stage it *also* looks different to the immune system.
And then when you consider that the parasite can hamper immune function and that it also can hide out, undetected, in body cells for years, and then come storming back… well. It’s a really hard problem. It’s taken a lot of trial and error to find the organism’s Achilles heel.
posted by disentir at 8:01 AM on July 24, 2023 [4 favorites]
There have been many efforts, over decades, to develop a vaccine. There is a lot of motivation to do so because malarial disease is holding back economic development in the regions where it is prevalent. But it’s a tough nut to crack because, for one thing, there are 4 different species of the malarial parasite that can infect humans and they each look different to the immune system. Even worse is that the parasite goes through many different life cycle stages in the human body, and at every stage it *also* looks different to the immune system.
And then when you consider that the parasite can hamper immune function and that it also can hide out, undetected, in body cells for years, and then come storming back… well. It’s a really hard problem. It’s taken a lot of trial and error to find the organism’s Achilles heel.
posted by disentir at 8:01 AM on July 24, 2023 [4 favorites]
mRNA is fundamentally different from all other vaccine technologies because it is essentially a payload that tells your cells (the ribosomes in particular) to build a specific protein. That's it! That's what it does. So the efficacy of the treatment is 100% dependent on how your body responds to that protein. For COVID, the vaccines produced the spike proteins of the virus, causing the body to produce antibodies and potentially, hopefully, memory T and B cells that would then know how to identify and attack COVID when it came calling.
For cancer vaccines, it depends on the cancer. Some cancers have known protein signatures which allow the specific mRNA payload to be produced at scale, and others are extremely specific to the patient. Hopefully - and this is a long, long way off if it even happens - at some point it will be cheap and quick to produce a custom mRNA payload which will make treating cancers and other aliments for which the mRNA mechanism can produce an effective therapy available to a wide variety of people from all socioeconomic groups. For now it is a long and involved process which makes it expensive.
The generic nature of mRNA means that some of the fundamental challenges - how to make it easier to store and transport, improving shelf life, simplifying and shortening the production chain - will apply to all mRNA therapies going forward. It's a bit like having an ISO standard or the introduction of interchangeable parts to industrial manufacturing. This means that work can be done independently on the application of specific protein signatures while other teams work on "how will we deliver this to the host." That is huge, that is revolutionary.
I'm very excited that it is being applied to malaria.
posted by grumpybear69 at 8:48 AM on July 24, 2023 [4 favorites]
For cancer vaccines, it depends on the cancer. Some cancers have known protein signatures which allow the specific mRNA payload to be produced at scale, and others are extremely specific to the patient. Hopefully - and this is a long, long way off if it even happens - at some point it will be cheap and quick to produce a custom mRNA payload which will make treating cancers and other aliments for which the mRNA mechanism can produce an effective therapy available to a wide variety of people from all socioeconomic groups. For now it is a long and involved process which makes it expensive.
The generic nature of mRNA means that some of the fundamental challenges - how to make it easier to store and transport, improving shelf life, simplifying and shortening the production chain - will apply to all mRNA therapies going forward. It's a bit like having an ISO standard or the introduction of interchangeable parts to industrial manufacturing. This means that work can be done independently on the application of specific protein signatures while other teams work on "how will we deliver this to the host." That is huge, that is revolutionary.
I'm very excited that it is being applied to malaria.
posted by grumpybear69 at 8:48 AM on July 24, 2023 [4 favorites]
Dip Flash: personally I loved the lariam/mefloquine dreams.
Yes, me too. They were very vivid and usually not scary in my case. It felt like going to the movies once a week.
posted by Too-Ticky at 9:48 AM on July 24, 2023 [1 favorite]
Yes, me too. They were very vivid and usually not scary in my case. It felt like going to the movies once a week.
posted by Too-Ticky at 9:48 AM on July 24, 2023 [1 favorite]
mRNA is fundamentally different from all other vaccine technologies because it is essentially a payload that tells your cells (the ribosomes in particular) to build a specific protein. That's it! That's what it does. So the efficacy of the treatment is 100% dependent on how your body responds to that protein.
But that part isn't unique to mRNA. Proteins are the key antigens in many/most vaccines, and how your body responds to it is generally the big question. If you code mRNA for proteins that don't cause an effective immune response, it won't work any better than a recombinant protein vaccine.
posted by mark k at 11:18 AM on July 24, 2023 [2 favorites]
But that part isn't unique to mRNA. Proteins are the key antigens in many/most vaccines, and how your body responds to it is generally the big question. If you code mRNA for proteins that don't cause an effective immune response, it won't work any better than a recombinant protein vaccine.
posted by mark k at 11:18 AM on July 24, 2023 [2 favorites]
What is unique about mRNA is that it your cells which are producing the proteins - all the mRNA is doing is providing the instructions.
posted by grumpybear69 at 11:25 AM on July 24, 2023
posted by grumpybear69 at 11:25 AM on July 24, 2023
Let's do a bit of malaria background, which will illustrate why every attempt to vaccinate for malaria has fallen short of what you'd want to see.
Background on an mRNA malaria vaccine from 2 years ago,.....please read about the SPECTACULAR difficulties that are posed by having an obligate vertebrate parasite that has developed immune evasion strategies....
posted by lalochezia at 12:39 PM on July 24, 2023 [3 favorites]
Background on an mRNA malaria vaccine from 2 years ago,.....please read about the SPECTACULAR difficulties that are posed by having an obligate vertebrate parasite that has developed immune evasion strategies....
posted by lalochezia at 12:39 PM on July 24, 2023 [3 favorites]
What is unique about mRNA is that it your cells which are producing the protein
Sure, but my point is that this is not a reason to expect an mRNA vaccine to work better than any other vaccine approach. There might be times it works better or worse, depending on various hard-to-predict factors, but a hard target, like malaria, is still a hard target. All the reasons that have made vaccine development especially hard here still apply.
I do agree with your point that there are quite possibly distributional advantages. Unfortunately that's not the bottleneck right now, because that could be solved regardless of vaccine tech.
posted by mark k at 12:51 PM on July 24, 2023
Sure, but my point is that this is not a reason to expect an mRNA vaccine to work better than any other vaccine approach. There might be times it works better or worse, depending on various hard-to-predict factors, but a hard target, like malaria, is still a hard target. All the reasons that have made vaccine development especially hard here still apply.
I do agree with your point that there are quite possibly distributional advantages. Unfortunately that's not the bottleneck right now, because that could be solved regardless of vaccine tech.
posted by mark k at 12:51 PM on July 24, 2023
@mark k:
The neat thing about mRNA is that, once you know what sequence you want, mRNA is (relatively) easy to make. Compared to actually making the antigens, in a form pure enough to inject into a human's body.
posted by Aardvark Cheeselog at 1:32 PM on July 24, 2023
The neat thing about mRNA is that, once you know what sequence you want, mRNA is (relatively) easy to make. Compared to actually making the antigens, in a form pure enough to inject into a human's body.
posted by Aardvark Cheeselog at 1:32 PM on July 24, 2023
Among the main reasons malaria is hard to prevent and treat is that it is a eukaryote, like us. Targeting bacteria and viruses is much easier because they are really different from our cells. For instance, a common antibiotic strategy is to target peptidoglycan, which is found in bacterial cell walls and (essentially) nowhere else on earth. Teaching the immune system to kill only certain eukaryotic cells and not others is exactly the reason cancer treatment and treatment for other eukaryotic infections like fungal and animal parasites are so challenging.
posted by hydropsyche at 3:08 PM on July 24, 2023 [4 favorites]
posted by hydropsyche at 3:08 PM on July 24, 2023 [4 favorites]
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