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So each turn, B-cells are presented with the latest version of the virus, they generate various antibodies to the various parts, and are graded at the end by how well the generated antibodies bind to the virus. The problem is that you have 1 million cells which bind strongly to the fake decoy targets and 1 cell which will bind not as strong to the real effective target. So this 1 cell never gets "promoted".
What this "germline targeting" multi-shot vaccine tries to do is to introduce a series of targets that stimulate that 1 in a million cell which will attack the right part of the HIV virus, so it gets "promoted", so if the real virus appears, the body will still go for the decoy targets, but will also generate a lot of these really effective 1 in a million cells, which got "promoted" previously by the vaccine.
To be more precise, you need to "guide" a lets call it B1 cell that all of us have in our repertoire to mutate into B2 then B3 than B4, because this B4 version will be capable of creating the right antibodies for HIV, the issue being that the intermediary states, B2, B3 are not naturally promoted so you very rarely get to the B4 state without this intervention.
The acquired immune system: a vantage from beneath
https://pubmed.ncbi.nlm.nih.gov/15539148/
Basically saying our immune systems ensure that microbes get ever more devious
However there’s ways that we counter that, like mucus that basically slowly feeds and tames your bacteria. Doesn’t work on viruses though
I would like to thank all the scientists who have dedicated all their hard work and ingenuity to eliminating the impact of cancer. Also, fuck cancer.
This is why it's hard to make a 'super vaccine' for flu, becuase it takes many rounds of shots to retrain some people's immune systems once they've latched on to the wrong recipe for antibodies.
this is called “original antigenic sin”
https://en.wikipedia.org/wiki/Original_antigenic_sin
An analogy of this is having the wrong math instruction in middle school could make your math classes harder at the university level.
It's an incredible system, and a product of probably a billion years of evolution since the first multicellular organisms had to protect themselves from infection.
If everyone was disciplined all the time in regard to everything, many problems in the world would simply not exist. But we live in reality where for whatever reason, people don't know to do something, or they do know and they're just not disciplined, or they make a mistake due to extenuating circumstances. And I would expect that the vast majority of people would oppose any idea of somehow punitively "dealing with" people who get some things wrong.
So I would say that it's very evidently not a practically solved problem, because if it were we wouldn't be looking to solve it still.
Within this reality, a vaccine is a great additional tool at solving the problem of preventing the spread of HIV.
At the risk of derailing this conversation from the original topic, those two things are not remotely equivalent. There's no organized political movement trying to tell people that seat belts and speed limits are immoral, and you should only drive when you're willing to accept the responsibility that comes with the risks.
Campaigning against _contraception_ feels like pretty much a dead issue, at least here; you just don’t see it anymore.
And my two examples are completely arbitrary because my point applies to pretty much any problem which would be solved by people being “more careful”.
So, political/religious elements aside, teen pregnancy and road safety are the same in terms of “if people were just more disciplined, there would not be these problems” (i.e. if teens who have easy access to contraceptives planned ahead before giving into impulsiveness; if drivers were more attentive to their behaviour), which I then pointed out is naive because the reality is that people aren’t perfect, they aren’t always disciplined, we’re all only human.
Hence, we need other solutions to help with problems which don’t require ignoring that people are only human and lack perfect discipline.
I agree that some organised movements can be a problem in that they can make other problems worse.
I rode in a lot of cars when I lived in Eastern Ukraine, 9/10 times or more the seatbelts had been removed or tucked behind the seats and not intended to be used. I got some very funny/annoyed looks when I first arrived and dug around in seats looking for a belt.
There's no need for a political movement when you already have the thing (no seatbelts).
You two might be using "discipline" pretty different. Your definition of discipline would encompass constant casual sex as long as contraceptives were used and any abortions were prompt, right?
I would caution against making an allusion to self control. It would be very cruel to act as if people who get a disease through no fault of their own could have avoided it, and most people who contract HIV could not. You may not have intended to make that allusion, but you did.
> So I would say that it's very evidently not a practically solved problem, because if it were we wouldn't be looking to solve it still.
This is obviously not what is meant by "practically solved problem". Everybody knows it is not actually solved.
It's quite sad and difficult to read at times.
This is factually untrue.
Being poor does not equal a HIV transmission rate. There is no 1:1 correlation.
A single protected (condom) sexual act between a male and female averages somewhere around 0.1-0.5% chance of pregnancy, and during the fertile window it could still be around 1% or more even with a condom.
Chance of HIV from one act of unprotected vaginal sex with an HIV-positive partner: ~0.08% male-to-female.
The high HIV transmission rates are NOT correlated with wealth, but social behavior. Unprotected anal sex with many partners? High risk. Now, Africa - the practice of dry sex contributes a ton to HIV transmission. Cultural belief that a dry vagina increases pleasure, hence woman use sand, chalk or bleach to dry out their vaginas, massively increasing HIV risk. Needle sharing of drug users? High HIV risk.
Not a class issue, no reason to punch down on poor people. Poor people have agency and many do not infect themselves with HIV in the first place.
I fully believe that HIV wouldn’t exist if PrEP had come out in the 80s when public hysteria was at an all-time high and the will to eradicate it was present.
You mean the time the US admin was intentionally neglecting the epidemic because "it's a gay disease"? Why do you think Reagan would have done anything to ensure such a medication was easily available?
Of course, and for good reason. The ones who know for a fact they are right, might in fact be wrong or malicious.
This whole "panic" seemed weird from the start, but once it becomes clear that it's from the lack of teen pregnancies it takes on an even creepier Epstein-like oddness.
HIV prevention is similar. We already have the tools. We have condoms. We have PrEP. Sure, a vaccine would be nice, but if someone is unwilling to go on PrEP, why would they suddenly be willing to get a vaccine?
Another tool isn't going to hurt, obviously. But it also isn't the #1 highest leverage place to be spending our time if the goal is to reduce HIV transmission. (It is, however, a great use of time to develop a vaccine if you're profit-motivated. HIV prevention is a massive business. 1 year of PrEP in the US costs $20-30k, although luckily ACA mandates $0 copay. I could imagine a $50k HIV vaccine being a blockbuster drug especially if ACA also mandates $0 copay - tons of money to be made! Ugh)
Edit: To be clear, I'm excited there's a promising vaccine. However, I am not getting my hopes up that a vaccine will magically cure all of the social/political issues getting in the way of a vaccine actually being widely distributed and administered.
Because PrEP at even its best and most modern version requires an update every six months for life. If you're well-off and in SF or NYC or London that might be easy, but there's so many externalities such as:
- People who misjudge the risk they're at, so don't go on the meds in the first place
- People who live in regions where getting to a doctor even every six months is a challenge
- The six-month injection is extraordinarily expensive and a life-time treatment, for a disease you don't even have yet.
If instead it becomes a once-in-a-lifetime series of shot, like many other vaccines are already, we can start considering a path to extinguishing the disease, not just teaching people to live with it.
Then there's the financial savings of a series of three shots once vs a lifetime of them.
A vaccine is something you do once and PrEP is something you have to continue to do over time and get overcharged out the ass for the entire time and worry about if it will remain available in the future.
Also, I believe that we just DOGEd our only vehicle for distributing these to underdeveloped nations.
If there were a pill that'd block pregnancy for X years, given at the age of Y, then parents could enforce it and teen pregnancy would be solved (also it'd be very cruel but I'm just trying to make a point so bear with me).
Going back to our topic: People could also forget PrEP, be drunk and forget to wear a condom and so on. If this vaccine (or vaccine series) creates a somewhat permanent protection, it'd make a huge difference.
Condoms? They break. More frequently than you might think.
Truvada and Descovy are great and make a big difference, but they require either high adherence to taking pills daily or being able to plan ahead for 2-1-1 (for same-sex relations - it's effectiveness for heterosexual intercourse hasn't been determined).
Apretude and Lenacapavir obviously require getting to a doctor or someone who can give you the injection either every other month or twice a year, is expensive, and can be very painful for some days afterward. And, of course, they're expensive.
A vaccine is the only real option for dealing with HIV for good.
The power of a vaccine is you can give it to adults and kids before they are sexually active and protect them, potentially, for the rest of their lives.
I'd also be curious to know if the combination of ART + the vaccine might cure someone of HIV. Which is also a pretty big deal.
"Gilead sells LEN at very high prices (over $28,000 per person per year in the US), severely restricts its supply to certain countries, and refuses to sell it directly to Doctors Without Borders/Médecins Sans Frontières"
Source: https://www.doctorswithoutborders.org/latest/campaigns/acces...
> I'd also be curious to know if the combination of ART + the vaccine might cure someone of HIV. Which is also a pretty big deal.
"Cure" in the sense they could become indefinitely under detectable levels. It's worth noting that to really cure a person of HIV you'd need to remove all mutated cells.
I agree that a vaccine is another game-changer, but it’s extremely important that we don’t spread misinformation about the efficacy and convenience of PrEP. In developed societies, it has already all but eliminated new transmissions among groups that were previously most at risk.
We also have education and stigma. While within the LGBT community it is far more common to be open about status and taking prep and doxy (far from perfect though), it still feels like outside of that the conversations are not happening as much as they should.
Throw in doctors that are not being proactive about the conversation.
Right now it seems like having prep and doxy is largely considered only if you are engaged in "risky" behavior (not saying that in a judgmental way to be clear), instead of just being sexually active and protecting yourself. Money and investment alone won't fix that, that is a societal shift around how we talk about sex.
That is also before we get into the cost issues in many other countries just for those that do need it.
Most people want to believe they are in a monogamous relationship and thus not having risky sex - even though they are the one cheating. Either PReP needs to be more common, are people need to stop their risky sex activities (that they are not even admitting to).
That blanket statement I very much disagree with. Sure there are side effects but that is part of why you also get tested every 3 months for liver issues (not that it is the only side effect, but still).
Instead of it being a blanket statement it should be a conversation with your doctor about the pros and cons.
You can still get HIV even if not engaging in risky behavior. Same with people getting pregnant when they did not intend too.
I am thinking college kids that are still figuring out their sexuality and exploring new things. You're going to make mistakes so having a conversation about prep with your doctor is a really good idea.
Condoms break. Partners lie. Shit happens.
It doesn’t take a lot for the risks to far outweigh any potential side effects. As far as I’m aware, every healthcare system in the developed world either recommends or enforces checkups after starting PrEP.
Vaccines are the "an ounce of prevention is worth a pound of cure"
Which countries are you talking about out of curiosity?
This doesn't cover all the reasons
I’m more familiar with malaria, where the preventative medicines are currently more effective than the vaccines.
The distinction is that a vaccine will train your immune system to actively destroy the foreign body, while a prophylactics might just prevent it from spreading or taking hold to begin with.
A vaccine is an objectively better solution than PrEP, just because of the time scale, PrEP needs discipline on a daily or x-monthly basis. A vaccine could last for years. Although, realistically, it's more likely to end up requiring yearly updates like COVID, because HIV is also a mutating son of a bitch.
I 100% agree that waiting for a vaccine is stupid beyond measure. The world should do both: make PrEP widely available AND keep funding vaccine research.
The answer to “are more tools really going to help” is always going to be “it depends.” Promising interventions sometimes fail entirely. If they statistically improve outcomes, that’s a win. Only occasionally is a disease entirely eradicated.
https://www.tumblr.com/squareallworthy/163790039847/everyone...
But of course it should be available to all that need it.
Also, even if it were a solved problem, the methodologies developed here can probably help with other viruses too in the future. This has already happened with the antivirals originally developed for HIV.
Access is a valid point. Perhaps the money being used to fund a superfluous vaccine should be used to fund access to PrEP in the Third World.
An astounding statement. Is it not possible that a vaccine giving decades of protection would give better health outcomes than doing PrEP every 6 months?
I take it you've never been to rural parts of Africa, Southeast Asia, Latin America.
It wouldn't be stopped, only slowed. You would still have transmission from accidental or unknown exposure. You would also have a small portion of the population that didn't care, regardless of the education.
either way, worth doing. you never know when circumstances might change and another tool in the toolbox becomes essential.
The reason we want a vaccine is because there's a huge logistics difference between a twice yearly injection and the real magic of something more like an MMR shot where one dose is usually effective for life.
Somehow we still need day after pills, abortions, antibiotics and other STD meds, and vaccines, now (hopefully) for HIV too.
So, clearly condoms are not the complete answer. Any solution that does not acknowledge the reality of how people actually behave is going to be imperfect.
We live in a messy world.
The total refusal for anyone at scale pretty much anywhere to use dental dams is particularly egregious:
https://www.theatlantic.com/health/archive/2019/04/dental-da...
https://slate.com/human-interest/2021/08/no-condoms-gay-sex-...
https://www.washington.edu/news/2024/02/27/qa-decline-in-con...
https://www.huffingtonpost.co.uk/entry/prep-condoms-gay-sexu...
At least a portion of the amount of people "in the closet" are closeted for fear of STDs, not particularly because of social stigma risk.
https://en.wikipedia.org/wiki/Ronald_Reagan_and_AIDS
Peer review files: https://media.springernature.com/original/springer-static/es...
Independent article covering it: https://cen.acs.org/pharmaceuticals/vaccines/hiv-vaccine-can...
Paid off it did not.
That being said, I don't understand enough to parse this very buzzword heavy release. Is this fundamentally different than the every 6 month vaccine we have now and is a more traditional vaccine or is it just continuing on that trend?
I agree it is far off from something in humans but it's a giant leap. The way I see it is like sending Laika in space before we send humans. It's significant and promising of a future where humans might have a vaccine.
It's a positive step, but still a fair way off for humans.
It might. You don't know that.
It seems like they’d be so useful - so there must be a good reason there aren’t lots of them normally?
This is in the "interesting advancement" stage, not "promising treatment."
Go team!
I distinctly remember Reagan cabinet members openly joking about all the people dying from it in WhiteHouse press briefing (basically Trump before Trump prototypes)
* https://en.wikipedia.org/wiki/Timeline_of_HIV/AIDS
Now if they could just do this for me-cfs/long-covid and related auto-immune diseases (there are over eighty) without the 50 year timeline please