5 ms·

HIV is incredibly sophisticated. It's actually kind of amazing how effective it is. I mean obviously the resulting disease is bad, no question. You can still ap

by cletus 5y ago

HIV is incredibly sophisticated. It's actually kind of amazing how effective it is. I mean obviously the resulting disease is bad, no question. You can still appreciate the sophistication. HIV has resisted efforts to develop a vaccine for 30+ years at this point. I am already beginning to wonder if the 2020s will be the story of the social transformation caused by mRNA vaccines. An effective and relatively cheap HIV vaccine will be huge. Apart from Covid and HIV, mRNA is going to have a huge effect on the flu vaccine too. For anyone who doesn't know, predictions are made about what flu strains will dominate the coming winter 4-6+ months ahead of time and the vaccine is made from that. Those predictions may not be accurate, which largely explains the variance of efficacy. mRNA has the potential to reduce that down to 1-2 months so you can potentially react to the actual dominant strains. Cancer of course isn't a single disease. Even something like lung cancer are a collection of different diseases. But some cancers are caused by viruses. A notable example is cervical cancer where it seems like most cases are caused by HPV strains. Australia is on track to essentially eliminate cervical cancer by 2035 [1]. To be clear, this isn't an mRNA vaccine. But mRNA vaccines may greatly reduce the time required to develop a vaccine and make it possible to eliminate whole classes of diseases. This is all super-exciting. [1]: https://www.vcs.org.au/blog/our-impact/news/australia-can-continue-to-pave-the-way-for-cervical-cancer-elimination/#:~:text=As%20a%20result%20of%20its,are%20down%20across%20the%20country https://www.vcs.org.au/blog/our-impact/news/australia-can-co....

athenot 5y ago
Agreed this very exciting. Malaria is also being targeted using the same technology. BioNTech announced they were working on it last month and some results[1] in mice are already looking promising. [1] Messenger RNA expressing PfCSP induces functional, protective immune responses against malaria in mice. https://www.nature.com/articles/s41541-021-00345-0 https://www.nature.com/articles/s41541-021-00345-0
vanadium 5y ago
It's worth posting Moderna's research pipeline to understand the breadth and depth of where they plan to take mRNA vaccines: https://www.modernatx.com/pipeline https://www.modernatx.com/pipeline
- X6S1x6Okd1st 5y ago
  Wow flu & RSV elimination would be great, especially for infants/toddlers
saalweachter 5y ago
Building out the capacity to manufacture and distribute ten billion doses of new vaccines as quickly as we can validate their safety and efficacy would also be quite the feat. It's nice for a first-world citizen that we were getting vaccinated against a new disease 12-18 months after it was first discovered, but with a big enough supply chain we could potentially be aiming to finish a world-wide vaccination campaign in 6-12 months, before we begin running up against the limits of our current methodologies for clinical trials.
Yajirobe 5y ago
How is HIV sophisticated? What makes it effective?
- ingalls 5y ago
  If you want a more-than-surface-deep (but not academic deep) article on what makes HIV fascinating - https://www.avert.org/professionals/hiv-science/overview https://www.avert.org/professionals/hiv-science/overview is a good quick read
- inasio 5y ago
  To me the "coolest" feature is that it saves dormant copies in cells, so that even if there is no detectable virus in the blood, a few months after stopping taking anti-HIV drugs the virus will reappear. If you sample the virus right when the first spike reappears, you will see a bunch of different HIV virus types, essentially the history of each mutation on that person, as each virus strain saves its own copies... (soon after the strongest strain dominates)
- betterunix2 5y ago
  A person with HIV will actually be infected by multiple variants simultaneously, since the virus mutates rapidly within a single host (tons of variants will be produced in a single day). So, even though the immune system will fight the virus and produce antibodies, the virus stays one step ahead. That also means that a person will not develop long-term immunity after being exposed to the live virus (and can even be infected multiple times with different variants and strains), and is the main challenge with developing an HIV vaccine. I am no expert but my understanding is that AIDS occurs when a variant targeting receptors more specific to CD4 T-cells begins replicating (or begins replicating at too high a rate), which results in T-cell counts falling below some threshold. So a person will go through an extended period without feeling any symptoms, possibly transmitting the virus to others (hence the importance of widespread, easy access to testing), only to be incapacitated by AIDS later when the "balance" of the variants changes (assuming they do not receive HIV-suppressing medications).
wizardofmysore 5y ago
What a wonderful time to be alive!
wodenokoto 5y ago
If all mRNA have side effects like the current crop of COVID vaccines I’m honestly not sure they are worth it as a seasonal flu shot. I’m not talking about the scare mongering of long term effects. Just the immediate. The day after my second moderna shot was worse than any flu I can remember and many of my friends in their 20s and 30s had to take a day off after their shot. I know several people in their 60s who had to take several days to a week in bed from vaccine side effects. That’s fine for ending a pandemic or curing HIV, but for seasonal flu? In terms of lost labor days, my anec-data points to this vaccine seeming worse than a seasonal flu.
- fallingfrog 5y ago
  It may be that the vaccine side effect severity is proportional to the severity of the disease it prevents. Also, these vaccines were very rapidly developed so perhaps the next generation of them will be a bit easier on the body.
  - incrudible 5y ago
    It is more likely the opposite - a strong immune system causes a strong vaccine reaction.
- Kluny 5y ago
  Like you said, it's anec-data. Among my friends, two were very sleepy the following day and otherwise fine. I had a sore arm for two days, and no other effects. My parents didn't have any noticeable effects.
  - hn_throwaway_99 5y ago
    But there is significant real data that the side effects from Moderna were significantly worse (but, again, not severe, and time-limited) than a flu shot. I know this is just another anecdote, but I get a flu shot every year and have never experienced anything more than a sore arm. With 2nd Moderna dose I had a fever of 103 and was completely out of commission for 36 hours.
agumonkey 5y ago
I have a similar feeling regarding cancer. It's a seemingly uncontrolled chaos that manages to paint itself into the sweetest spot to keep growing .. so many positive reinforcement failures it's eery
klipt 5y ago
> cervical cancer where it seems like most cases are caused by HPV strains What's funny is the US initially only vaccinated women against HPV because "men can't get cervical cancer". Then it turned out lots of men were getting oral/throat cancers from oral HPV acquired from oral sex. Oops!
- kcarter80 5y ago
  Source?
  - klipt 5y ago
    https://www.mdanderson.org/publications/focused-on-health/what-men-need-to-know-about-hpv-related-throat-cancer.h12-1593780.html https://www.mdanderson.org/publications/focused-on-health/wh... > HPV-related throat cancer is on the rise, and the typical patient is a male in his 50s or 60s.
- inasio 5y ago
  The bigger issue was anal cancer among men that have sex with men, if I remember correctly the risk was around 100x than in the general population, and also completely preventable by the HPV vaccine.
  - lebuffon 5y ago
    I am still wondering how many other cancers are caused by viruses that we have not isolated or maybe choose not to search for because "conventional wisdom" The trail of bread crumbs seems to be there. - HPV - Hep C - Human T-cell leukemia/lymphoma virus (HTLV)
- t-writescode 5y ago
  Source for this, and the amount of time that we were only vaccinating women? If it was just a year or so, that's a very different story from decades. I recall there being a sudden, loud push 10ish years ago, for everyone to get the HPV vaccine. There were some anti-vax arguments against it for the same reason as there's resistance to sex ed; but no "men can't get cervical cancer" arguments, that I recall.
vmception 5y ago
I've been having difficulty trying to think about how much Moderna will charge for their other products like the covid one is sold at super low prices compared to what would normally be possible but the other products won't have nearly as many customers either what do you guys think?
- hinkley 5y ago
  If the argument is that you can make mRNA vaccines faster, that would also tend to imply cheaper. Which could mean they can make it up on volume.
selcuka 5y ago
> But some cancers are caused by viruses. Note that mRNA technology is not limited to viruses. The cancer vaccine is actually a misnomer as it is actually a personalized treatment for people who already have cancer [1]: > The cells from the patient's tumor are analyzed, and genetic sequencing is used to identify twenty neoantigen epitopes that may elicit the strongest immune response in the patient. The sequences encoding the twenty patient-specific epitopes are transcribed and loaded onto a single mRNA molecule. [...] This leads to an induction of both cytotoxic T-lymphocyte (CTL)- and memory T-cell-dependent immune responses that specifically target and destroy the patient's cancer cells that express these neoantigens. BioNTech has actually started Phase 2 trials for a mRNA-based cancer therapy [2]. [1] https://www.cancer.gov/publications/dictionaries/cancer-drug/def/mrna-based-personalized-cancer-vaccine-mrna-4157 https://www.cancer.gov/publications/dictionaries/cancer-drug... [2] https://www.clinicaltrialsarena.com/news/first-patient-dosed-in-biontech-phase-ii-trial-of-mrna-cancer-vaccine/ https://www.clinicaltrialsarena.com/news/first-patient-dosed...
- HeadsUpHigh 5y ago
  Back when I was a freshman in medicine studying immune responses this kind of personalized medicine was my wet dream. This was less than 10 years ago. This is incredible how fast it's moving.
tomjen3 5y ago
>I am already beginning to wonder if the 2020s will be the story of the social transformation caused by mRNA vaccines. An effective and relatively cheap HIV vaccine will be huge. In the 90s, sure. Between treatment so effective that you can't pass it on and PreP, the days of HIV is over anyway. Vactination might be a bigger deal in poor countries, but they are also the countries that can least afford it. If they can cure HIV, that would be another thing.

by cletus 5y ago

athenot 5y ago

Agreed this very exciting. Malaria is also being targeted using the same technology. BioNTech announced they were working on it last month and some results[1] in mice are already looking promising. [1] Messenger RNA expressing PfCSP induces functional, protective immune responses against malaria in mice. https://www.nature.com/articles/s41541-021-00345-0 https://www.nature.com/articles/s41541-021-00345-0

vanadium 5y ago

It's worth posting Moderna's research pipeline to understand the breadth and depth of where they plan to take mRNA vaccines: https://www.modernatx.com/pipeline https://www.modernatx.com/pipeline

X6S1x6Okd1st 5y ago
Wow flu & RSV elimination would be great, especially for infants/toddlers

saalweachter 5y ago

Building out the capacity to manufacture and distribute ten billion doses of new vaccines as quickly as we can validate their safety and efficacy would also be quite the feat. It's nice for a first-world citizen that we were getting vaccinated against a new disease 12-18 months after it was first discovered, but with a big enough supply chain we could potentially be aiming to finish a world-wide vaccination campaign in 6-12 months, before we begin running up against the limits of our current methodologies for clinical trials.

Yajirobe 5y ago

How is HIV sophisticated? What makes it effective?

ingalls 5y ago
If you want a more-than-surface-deep (but not academic deep) article on what makes HIV fascinating - https://www.avert.org/professionals/hiv-science/overview https://www.avert.org/professionals/hiv-science/overview is a good quick read
inasio 5y ago
To me the "coolest" feature is that it saves dormant copies in cells, so that even if there is no detectable virus in the blood, a few months after stopping taking anti-HIV drugs the virus will reappear. If you sample the virus right when the first spike reappears, you will see a bunch of different HIV virus types, essentially the history of each mutation on that person, as each virus strain saves its own copies... (soon after the strongest strain dominates)
betterunix2 5y ago
A person with HIV will actually be infected by multiple variants simultaneously, since the virus mutates rapidly within a single host (tons of variants will be produced in a single day). So, even though the immune system will fight the virus and produce antibodies, the virus stays one step ahead. That also means that a person will not develop long-term immunity after being exposed to the live virus (and can even be infected multiple times with different variants and strains), and is the main challenge with developing an HIV vaccine. I am no expert but my understanding is that AIDS occurs when a variant targeting receptors more specific to CD4 T-cells begins replicating (or begins replicating at too high a rate), which results in T-cell counts falling below some threshold. So a person will go through an extended period without feeling any symptoms, possibly transmitting the virus to others (hence the importance of widespread, easy access to testing), only to be incapacitated by AIDS later when the "balance" of the variants changes (assuming they do not receive HIV-suppressing medications).

wizardofmysore 5y ago

What a wonderful time to be alive!

wodenokoto 5y ago

If all mRNA have side effects like the current crop of COVID vaccines I’m honestly not sure they are worth it as a seasonal flu shot. I’m not talking about the scare mongering of long term effects. Just the immediate. The day after my second moderna shot was worse than any flu I can remember and many of my friends in their 20s and 30s had to take a day off after their shot. I know several people in their 60s who had to take several days to a week in bed from vaccine side effects. That’s fine for ending a pandemic or curing HIV, but for seasonal flu? In terms of lost labor days, my anec-data points to this vaccine seeming worse than a seasonal flu.

fallingfrog 5y ago
It may be that the vaccine side effect severity is proportional to the severity of the disease it prevents. Also, these vaccines were very rapidly developed so perhaps the next generation of them will be a bit easier on the body.
- incrudible 5y ago
  It is more likely the opposite - a strong immune system causes a strong vaccine reaction.
Kluny 5y ago
Like you said, it's anec-data. Among my friends, two were very sleepy the following day and otherwise fine. I had a sore arm for two days, and no other effects. My parents didn't have any noticeable effects.
- hn_throwaway_99 5y ago
  But there is significant real data that the side effects from Moderna were significantly worse (but, again, not severe, and time-limited) than a flu shot. I know this is just another anecdote, but I get a flu shot every year and have never experienced anything more than a sore arm. With 2nd Moderna dose I had a fever of 103 and was completely out of commission for 36 hours.

agumonkey 5y ago

I have a similar feeling regarding cancer. It's a seemingly uncontrolled chaos that manages to paint itself into the sweetest spot to keep growing .. so many positive reinforcement failures it's eery

klipt 5y ago

> cervical cancer where it seems like most cases are caused by HPV strains What's funny is the US initially only vaccinated women against HPV because "men can't get cervical cancer". Then it turned out lots of men were getting oral/throat cancers from oral HPV acquired from oral sex. Oops!

kcarter80 5y ago
Source?
- klipt 5y ago
  https://www.mdanderson.org/publications/focused-on-health/what-men-need-to-know-about-hpv-related-throat-cancer.h12-1593780.html https://www.mdanderson.org/publications/focused-on-health/wh... > HPV-related throat cancer is on the rise, and the typical patient is a male in his 50s or 60s.
inasio 5y ago
The bigger issue was anal cancer among men that have sex with men, if I remember correctly the risk was around 100x than in the general population, and also completely preventable by the HPV vaccine.
- lebuffon 5y ago
  I am still wondering how many other cancers are caused by viruses that we have not isolated or maybe choose not to search for because "conventional wisdom" The trail of bread crumbs seems to be there. - HPV - Hep C - Human T-cell leukemia/lymphoma virus (HTLV)
t-writescode 5y ago
Source for this, and the amount of time that we were only vaccinating women? If it was just a year or so, that's a very different story from decades. I recall there being a sudden, loud push 10ish years ago, for everyone to get the HPV vaccine. There were some anti-vax arguments against it for the same reason as there's resistance to sex ed; but no "men can't get cervical cancer" arguments, that I recall.

vmception 5y ago

I've been having difficulty trying to think about how much Moderna will charge for their other products like the covid one is sold at super low prices compared to what would normally be possible but the other products won't have nearly as many customers either what do you guys think?

hinkley 5y ago
If the argument is that you can make mRNA vaccines faster, that would also tend to imply cheaper. Which could mean they can make it up on volume.

selcuka 5y ago

> But some cancers are caused by viruses. Note that mRNA technology is not limited to viruses. The cancer vaccine is actually a misnomer as it is actually a personalized treatment for people who already have cancer [1]: > The cells from the patient's tumor are analyzed, and genetic sequencing is used to identify twenty neoantigen epitopes that may elicit the strongest immune response in the patient. The sequences encoding the twenty patient-specific epitopes are transcribed and loaded onto a single mRNA molecule. [...] This leads to an induction of both cytotoxic T-lymphocyte (CTL)- and memory T-cell-dependent immune responses that specifically target and destroy the patient's cancer cells that express these neoantigens. BioNTech has actually started Phase 2 trials for a mRNA-based cancer therapy [2]. [1] https://www.cancer.gov/publications/dictionaries/cancer-drug/def/mrna-based-personalized-cancer-vaccine-mrna-4157 https://www.cancer.gov/publications/dictionaries/cancer-drug... [2] https://www.clinicaltrialsarena.com/news/first-patient-dosed-in-biontech-phase-ii-trial-of-mrna-cancer-vaccine/ https://www.clinicaltrialsarena.com/news/first-patient-dosed...

HeadsUpHigh 5y ago
Back when I was a freshman in medicine studying immune responses this kind of personalized medicine was my wet dream. This was less than 10 years ago. This is incredible how fast it's moving.

tomjen3 5y ago

>I am already beginning to wonder if the 2020s will be the story of the social transformation caused by mRNA vaccines. An effective and relatively cheap HIV vaccine will be huge. In the 90s, sure. Between treatment so effective that you can't pass it on and PreP, the days of HIV is over anyway. Vactination might be a bigger deal in poor countries, but they are also the countries that can least afford it. If they can cure HIV, that would be another thing.