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A Trial HIV Vaccine Triggered Elusive and Essential Antibodies in Humans (dukehealth.org)
282 points by geox 8 months ago | hide | past | favorite | 68 comments



Animation of how HIV infects a single T-cell

https://vimeo.com/260291607


Can you post this as a new submission? I want to read knowledgeable peoples' responses to it! :)

Viruses are incredible. This video does a great job of illustrating how HIV in particular seems to hijack so many essential systems. I now feel like I have a deeper appreciation for why "cures" for viruses are like a holy grail technology – how could you even prevent something like this without collateral damage to some perfectly healthy + necessary process? They're so tangential to how our cells need to work that they're almost parallel.



The level of detail in the knowledge of the process is astounding. Having never studied anything like this, at every stage I kept thinking: how do we know all of this?


If you liked that - this one on the cell’s energy systems blew me away when I first saw it https://youtu.be/LQmTKxI4Wn4?si=7KEKwFjfLrwyCLvW


This is amazing. Where do all the free protons come from?


Easy, thousands of smart, motivated people, billions of dollars invested and decades of work!


Watching the video I did indeed feel like "this is insane!" all the way through...


People being born and growing up to decide that "this is what I'm gonna do"

Also wealthy individuals or companies funding research purely for public good, often with little to no prospect of returns.


The vast majority of what we know would be due to public funding. Not private donors.


Ya I would agree there


For me the most incredible part of the video is the transcription process. Looks like the head of a Turing machine going through the "tape". Really amazing that something like this occurs in the body at a nanometric scale.


I was about to say a lisp macro but turing tape works fine too ;)


This video invokes fear in me. Like, those alien machines (viruses) are doing their weirdo stuff countless times a second in my body. Horrifying.


If it helps, consider that "your body" is the-same-or-more dangerously impressive, with layers of hideously effective defenses to displace or starve or murder anything that gets close, a swarming hive of unfathomable nanotechnology winnowed over millions of years of adversity between the many inheritors of an ancient grey-goo apocalypse.

Just from one eldritch hive-mind to another.


I'm not afraid of the viruses per se, I trust in my immune system. It's more the extreme intricacy of the whole damn meatbag. Kinda like looking up at the stars in an ultra-dark environment and seeing more stars than you've ever seen before. I get a little dizzy. Don't get me started on math.


If math can make you feel awe, you've got to watch the Numberphile series on very big numbers. They're constants used in proofs that are specific, well-defined integers known to be finite, but so huge that the physical universe does not have enough particles (or even Plank-scale microstates) in it to represent the number of digits these numbers have! Absolutely mind-bending stuff.

Listed in increasing order:

"Graham's Number" https://www.youtube.com/watch?v=XTeJ64KD5cg

"How Big is Graham's Number? (feat Ron Graham)" https://www.youtube.com/watch?v=GuigptwlVHo

"The Enormous TREE(3)" https://www.youtube.com/watch?v=3P6DWAwwViU

"TREE(3) (extra footage)" https://www.youtube.com/watch?v=IihcNa9YAPk

"The Daddy of Big Numbers (Rayo's Number)" https://www.youtube.com/watch?v=X3l0fPHZja8


Maybe you are talking about "awe"?

https://en.wikipedia.org/wiki/Awe


Yup!


That's why I consider biology a type of alien technology that we've been trying to reverse engineer but are still a ways away.


There's even some great Kurzgesagt videos on it.

https://www.youtube.com/watch?v=lXfEK8G8CUI


Damn... And proteins are not living organisms, but the video makes them look like autonomous agents and even states thing like "the virus recruits new proteins". Is this mostly an anthropomorphization of the events, or did I miss the relevant episode of biology?


> Is this mostly an anthropomorphization of the events

Yes.

Basically everything is bumping around until the desired reaction or configuration is obtained. The irrelevant proteins are generally not shown.

The length scales involved are extremely short so the chaotic soup works itself into configuration shockingly quickly.

There are also membranes, vesicles, and organelles (e.g. Golgi) that partition, package, and redistribute proteins so that they tend to be more concentrated where required.


> Basically everything is bumping around until the desired reaction or configuration is obtained.

Dare I say it? That sounds alot like what we do in the office most of the time.


"Employing an bio-mimic evolutionary compilation algorithm" does sound better than "changing things semi-randomly until it compiles and passes the tests".


This post or something similar has been posted to HN before: http://www.righto.com/2011/07/cells-are-very-fast-and-crowde...

It makes a lot more sense when described from this perspective:

>You may wonder how things get around inside cells if they are so crowded. It turns out that molecules move unimaginably quickly due to thermal motion. A small molecule such as glucose is cruising around a cell at about 250 miles per hour, while a large protein molecule is moving at 20 miles per hour. Note that these are actual speeds inside the cell, not scaled-up speeds. I'm not talking about driving through a crowded Times Square at 20 miles per hour; to scale this would be more like driving through Times Square at 20 million miles per hour!

>Because cells are so crowded, molecules can't get very far without colliding with something. In fact, a molecule will collide with something billions of times a second and bounce off in a different direction. Because of this, molecules are doing a random walk through the cell and diffusing all around. A small molecule can get from one side of a cell to the other in 1/5 of a second.

>As a result of all this random motion, a typical enzyme can collide with something to react with 500,000 times every second. Watching the video, you might wonder how the different pieces just happen to move to the right place. In reality, they are covering so much ground in the cell so fast that they will be in the "right place" very frequently just by chance.


Protein folding freaks me out too.


It freaks me out too. At the same time, the fact that we know so much about biology comforts me - we can build our own little machines :)


The music sure doesn’t help!


That is really impressive animation, now I'd love to see this animation updated to include how the Vaccine works


It's wild to think what goes into making a life happen. It's so alien, and so complex that it's hard to even realize where "the person" starts compared to the rest of the world. That video is just mind bending.


There should be yearly awards for good science animations and learning tools like this



I've heard about membrane protein enables interaction with outside molecules that are random walking near the cell membrane, but seeing it as an animation really hit me that that's how things work.


Feels like a heist movie. Breaking into the cell and hijacking it's machinery to make more of itself.


Very good, but I could do without the ominous music


Very interesting, thanks for posting.


This is equal parts amazing and terrifying.


Really incredible animation.


Wow!


The music is amazing.


Actual paper is here: https://www.cell.com/cell/fulltext/S0092-8674(24)00459-8

God knows why a press release wouldn't provide a direct link


> Other features of the vaccine were also promising, most notably how the crucial immune cells remained in a state of development that allowed them to continue acquiring mutations, so they could evolve along with the ever-changing virus.

As I understand it, somatic hypermutation is a process that only occurs within germinal centers.

Is that what is happening here?



How could the press release not link to it shakes head


Very promising outcome. But I wonder they/why we are just learning about this now when it seems that the inoculations occurred in 2017?


It's not really valuable if the immunity isn't very durable. There are already short duration things like PREP. If it's been 5 years (2019), that's a big deal.


There is a injectable every 2 months solution now.

https://www.fda.gov/news-events/press-announcements/fda-appr...


I have a friend who takes this; it's very expensive and insurance doesn't want to pay for it, but if you convince them that you're high enough risk ("oh, I just keep finding myself in strangers' beds, I love getting people's blood on me, and I'm just too dumb to remember to take a pill every day"), you can get it.

Normal PrEP actually puts you at greater risk if you forget to take it, so I'm really glad that the injectable one is an option. It's much more effective, too. I should see about trying to get on it soon...


> oh, I just keep finding myself in strangers' beds

Honestly, that‘s why I am taking daily prep. Can‘t trust my urges and I am tired of telling siri to remind me of a HIV test in 4 weeks…


Pretty sure you're still supposed to be testing - it's not 100% effective.


I am, since there are plenty of other things, all of which I had and you get tested in a whole package. You actually don’t get a new prep prescription without it, since they also do bloodworks for the kidney and liver. I always get tested at latest one month after my last sexual contact, unless it so happened I did not have any bare sex, wasn‘t on prep and don‘t need a new prescription. The non 100% effectiveness, honestly, I just don‘t even want to think about it…


Yeah, that's why I'm saying years long protection would be a huge shift from the current short term stuff.


The paper was published on Friday.


Perhaps this could be a beneficial prophylaxis. And having another treatment that uses CRISPR to remove the provirus is also an essential to have a durable cure for patients already infected. https://www.bbc.com/news/health-68609297


Look up EBT 101. Human trials started last year for a CRISPR based cure for HIV. This is from the same team that was able to cure SIV in monkeys using the same technique.


My layman, super naive understanding is that an HIV vaccine could also help an HIV-positive person (with a well-managed HIV infection), because it dampens transmission from infected to uninfected cells.


I am not an immunologist... I don't understand biology very well. How significant is this? Is it even trustworthy?


The fact they can trigger antibodies on a stable portion of the virus is impressive. Near the end, it sounds like a multi pronged approach is needed to deal with variations. I’m not an immunologist, but it was pretty light. If they are in trials does that indicate they have a white paper?


"If they are in trials does that indicate they have a white paper?"

I would think they'd have to in order to have the trial. It probably is not for public distribution though.


Clinical trial data gets published online, might be able to find what you're looking for.


I'm not an expert on this stuff at all, so assume I'm stupid and ignorant when I write the following. As I understand it, HIV has actually been useful to develop a delivery mechanism for some therapies that have excellent potential. Would this kind of vaccine cause such therapies to become ineffective?


No: because the target of vaccines is viral protein coats to prompt antibody binding. The usefulness of HIV for other applications is that some of it's proteins - i.e. the reverse transcriptase - are extremely useful molecular engineering tools, but they're used as individual components.

One of the interesting failed COVID vaccine efforts was by the University Of Queensland in Australia which was working on a novel protein based vaccine where the idea was a conformationally locked COVID spike protein was injected[1] - basically it presents the protein as it's found on the surface of the virus, which in turn promotes an antibody response which is "accurate" - whereas free-floating proteins, i.e. if you just shredded up the virus - don't look the same.

The problem? The technology was based on a protein sequence called gp41 - which is a subunit of the HIV spike protein. It's not HIV, it's not derived from actual HIV virus - it's made in labs from separately cloned sequences...but unfortunately, part of the immune response to the vaccine generated HIV binding antibodies, similar enough to "real" HIV binding antibodies that they would trip false-positives in HIV tests - i.e. you would test positive to HIV for months, but you didn't actually have HIV - you had antibodies which had enough activity to the common HIV test assay that it looked like you did (e.g. a PCR test for HIV would show you don't have it. But it's impractical to have a whole lot of people who look indistinguishable to the HIV positive population when we had other vaccine options).

[1] https://www.nature.com/articles/d42473-020-00504-2


Does this university press release name-check Cell but not link to the article? A bit frustrating.



Thank you.


I wonder about the potential for varied immune responses across different populations.


woah, how exciting!




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