The way the HIV evades effective antibodies is by tricking the immune system to generate antibodies for fake decoy targets that the virus will immediately mutate.

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.

This is the way a lot of modern cancer vaccines are being developed. The idea is to create custom vaccines in the future targeting the patients specific cancer. So they are therapeutic vaccines. Obviously some cancers cannot be reach by a vaccine or are so aggressive that they overwhelm the patient before they can help.

Well, they kind of all work that way, it's just that most of the curriculum occurs naturally through interactions with wild pathogens

All vaccines are training data for the immune system, which is a learning machine whose operation is a little bit like a genetic algorithm. It generates and sieves variation using a vocabulary of pre-encoded building blocks to fit the targets it's presented with.

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.

I do not see what is impressive here at all. The immune system constantly yields new antibodies targeting different epitopes - all the time. THAT is what is impressive, not multi-vaccines trying to induce shifts towards certain epitopes over others.

You could say the same about teen pregnancy being a practically solved problem, except there is still the problem of teen pregnancy. Or even something more mundane as driving consistently safely all the time to solve the problem of accidents.

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.

It's a solved problem if you are someone that knows you'll be exposed to HIV in the very near future and you have the money and wherewithal to purchase PrEP before that event (and you can plan the event 7 days out).

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.

Cost and compliance are still 2 major factors that have not been solved.

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.

It is endemic in the simian population. It will keep crossing over into humans again and again. It has done it before several times. People who live near forests would have to be on Prep everyday of their lives. The reason they eat bushmeat is the because they are poor and will be too poor to afford daily medication. A once-and-done vaccine would at least stop new crossovers. Only then could we really get a handle on ending this disease world-wide.

This is the wrong take. You are basically arguing that if we have one solution, why bother having a second one?

prep is great but i would really rather take a one-time vaccine than be expected to take an expensive pill forever that could mess up my liver

Isn’t prep more like a prophylactic, as opposed to a a vaccine?

I’m more familiar with malaria, where the preventative medicines are currently more effective than the vaccines.

Transportation was a solved problem with horses, doesn't mean the car isn't a good idea. Same for internal combustion and EVs.

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.

There are some dubious metaphors in use here. Public health is not about math problems to be “solved.” “A solution exists” is just a milestone. “We just have to use them” - yes, but leave out “just,” there is more to do and it’s hard.

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.

There's still a huge difference between a one off injection and lifelong tablets.

For rich people (meaning the ~3 billion people that have some sort of access to medical infrastructure), it is a solved problem, but there are quite many people without any access to it. Even for those "solved problem" people, taking a pill every day to be protected is inconvenient. They might not take it every day, etc.

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.

Those on prep would welcome a vaccine, it would be a significant improvement. I agree that this is no reason to take the foot off the gas with prep availability, we need more ASAP.

PrEP is difficult on the body over time and though it can be used if you are high risk you are meant to avoid certain medications while using it and have to do follow ups with your doctor to check organ functions.

it's actually an interesting question: is there a point where the long acting prep injections have effective durations that look like vaccines and boosters. and yes, sadly, it appears that convenience and some of the psychological aspects of marketing play outsized roles in public health.

either way, worth doing. you never know when circumstances might change and another tool in the toolbox becomes essential.

In the global south a significant barrier is the lack of sex education, driven by local christian associations, which have significant power in local societies. They see it as "gender ideology" or as preventing births and thus being against the bible.

"The ongoing loss of life and health due to HIV could be stopped if we cared enough to invest resources in wide-scale PrEP availability and public health education."

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.

My hiv exposure was from an SA, I wasn’t on Prep. This will still save lives!

Who's waiting? The problem is the populations we need to distribute it to can least afford it.

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.

Everything is a "solved problem" if you're willing to ignore a variable (usually money or human life/toil).

This isn't just about HIV, it's about finding new ways to approach viruses. HIV wasn't the first and won't be the last virus we don't have a way to stop. This research adds to our knowledge about ways to attack some of the trickier viruses.

It's a problem that was "solved" long before that by just wearing a condom and protecting yourself against other diseases too, and even pregnancy. Condoms are cheap, widely available and decades of condom-related education has been given out to many different generation of kids and adults worldwide.

Somehow we still need day after pills, abortions, antibiotics and other STD meds, and vaccines, now (hopefully) for HIV too.

Public health education means getting gay men to start wearing condoms or dental dams and apparently that's a bridge too far for them.

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.

Project 2025 vehemently goes against of it. Why was I downvoted? I am right. The american government strides in lockstep with P25 and corruption.

Nobody else said it, so I will. Halting HIV transmission is a solved problem if people are willing to give up sex with untested strangers. The same is true of syphilis, monkeypox, and every other sexually transmitted disease. It says a lot about human nature that a small number of people would rather have society spend vast sums of money researching and developing prophylactics and vaccines instead of changing their own behavior, while the vast majority have enough self-control not to catch diseases through random sex.

> The ongoing loss of life and health due to HIV could be stopped if we cared enough to invest resources in...public health education.

It's definitely a problem of caring, but not one of education: there are not honestly many people out there who don't know that random sex leads to diseases, but there are some people who just don't care enough to prevent their spread. If they did care, they would have sex only with known, tested partners. Minimizing harms through additional investment of resources just leads people to continue to fail to care, at society's expense.

I invested in Moderna around the time they had their vaccine enter Phase I trials, hoping for a pay off.

Paid off it did not.

It doesn't need to be 100% effective in humans, it just needs to slow transmission enough such that the rate of incidence declines in the direction of eradication.

The reason why this is a big deal is because they figured out a way to engineer the type of cells that are hard to create that can readily fight off the virus. In some people they create them already. Here they were able to get the body to create them.

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.

Long-acting antiretroviral injection ≠ vaccine

We don't need an expert even - pre-clinical is a far ways off even if successful.

This is in the "interesting advancement" stage, not "promising treatment."

The people who would "let their guard down" did long before this news. (Or Prep, for that matter.)

Well that's definitely a take. I'm not going to be the first in line to defend government, but more often than not I'm seeing friends and family getting chased out of the hospital BEFORE they should be.

You don’t recover from HIV at home. We tried that in the 80’s because we had to.