Hacker News Reader

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

> 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...

[2] https://www.clinicaltrialsarena.com/news/first-patient-dosed...

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.

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

Wow flu & RSV elimination would be great, especially for infants/toddlers

> 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!

Source?

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.

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.

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)

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.

As of 2017 WHO was still recommending prioritizing girls under 15 for vaccination: https://www.who.int/immunization/policy/position_papers/pp_h...

> Vaccination of secondary target populations e.g. females aged ≥15 years or males, is only recommended if feasible, affordable, cost-effective and does not divert resources from vaccinating primary target population or from effective cervical cancer screening programmes.

I think the tone I read implied into your post was that it was something malicious or arrogant. "Don't protect the men because they don't need to care about giving it to women", followed by "oh noes, men can get sick too! Better protect them!" rather than a resource allocation problem, as the quote is arguing.

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.

>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.

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.

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.

It is more likely the opposite - a strong immune system causes a strong vaccine reaction.

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.

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.

I think they just took the highest dose that had acceptable side effects because they had no time to figure out the perfect dose.

This is also my thinking, and doesn't seem too implausible given that the dosage is so much higher than Pfizer (100mcg vs 30mcg). My relatives who got Moderna had similar reports to some of the posters above. I got Pfizer and barely noticed.

>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.

It's all relative. The side effects from a flu shot are mild compared to the flu. Ditto for the Moderna vaccine.

do all mRNA vaccines have to be multi-dose?

I'm sure a second shot of the traditional flu vaccine wouldn't feel great.

I don't know. The last time I had a seasonal flu, I was sick for a week. I cried because I needed to do laundry and simply didn't have the energy and I ate poorly - I lived alone at the time. All of my energy went to surviving work.

Compared to having a sore arm for a couple of days? Or even getting sick for a day or two - at a time I can choose - to just not deal with getting sick later on? Sure. And I'm awfully sure that the flu kills more than the vaccine for it. So many complications for so many people.

And to be fair: The folks you knew in their 60's had an unusual reaction. Older people with their aging immune systems are actually more likely to get little to know side effects to vaccines - younger folks tend to get more. The same goes for folks that are genetically female: You tend to get more side effects (they think this is because so many immune genes are on sex chromosomes, and women have more genes here.).

And to be fair: Taking a day off of work when you are sick isn't such a big deal if you live somewhere with labor protection laws that allow you sick days. It is a little less of a big deal if you live in the US and get paid sick time, but a lot of folks just don't have this so it makes being sick after a vaccine a bigger deal that it should be.

It's possible you never had a flu. It's pretty rough

I've had Moderna and the flu, and they were about equally bad ("I can move, but only because I'll wet the bed otherwise, please God let me sleep so it stops feeling like my bones are dissolving") but Moderna lasted only a day whereas the flu lasted several. I think you'll struggle to argue convincingly that Moderna doesn't commonly have awful side effects :P

You also didn't pass the Moderna side-effects to anyone else, unlike with the flu.

The worst case of flu I had lasted a month. It's usually several days of chills, aches, and coughing.

With the second phizer shot, I mild symptoms for a day.

The question is simple, does the benefit of using said vaccine or medication outweigh the risk of not using it. In the case of covid being sick for a couple of days and a guarantee of preventing future death is better than a resulting death had the user not taken it.

I would say a couple of days of flu is vastly better than some of the other side effects I've seen with other medications. Take for instance:

- Suicidal thoughts - Abnormal heart rhythms - Internal bleeding - Cancer

At the end of the day, we rely on medical professionals to help us with these decisions and weigh the treatment of said ailments against the side effects we may incur if we do or don't take treatment. For what it's worth I've seen the opposite, most folks took the day off just in case there was a side effect, but ultimately everyone was fine. I know I scheduled my vaccine shots for a Thursday so I could have a 3 day weekend assuming I wasn't feeling ill, and I felt fine so I enjoyed my 3 day weekend.

This is fair since existing flu vaccines are seems to fine and flu medication is available, but good to have mRNA option.

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

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?

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.

How is HIV sophisticated? What makes it effective?

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 is a good quick read

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)

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).

What a wonderful time to be alive!