Submitted by ShelfordPrefect t3_10kye24 in askscience
FellowConspirator t1_j5urcxn wrote
To make a vaccine, the thing that you are making a vaccine against (typically a virus) needs to have a prominent protein on it's surface. The vaccine can be inactive virus, or parts, it doesn't matter, you just need to provide the foreign protein to the immune system so that it can learn to recognize it so when a virus tries to infect, the body is prepared to stop it.
Viruses mutate over time, and if the protein on the outside tends to change a lot, it can be difficult to make a vaccine against. It turns out that small changes in the protein can really change the shape, and it's the shape that the immune system recognizes. The other thing that can make it tricky is that some viruses tend to carry a bubble of fat around them that hides the protein so the immune system can't see it.
HIV is difficult because it has another trick up it's sleeve: it attacks the immune system itself, meaning that if it gets a foothold, a vaccine would be useless because your immune system can't fight back. AIDS, the disease caused by HIV, happens with the immune system pretty much fails because the virus has disabled it. The person starts getting all sorts of infections and cancers that they wouldn't normally get, and that's what makes it deadly.
COVID-19 was simple, for a few reasons: we're already familiar with this type of virus (we've known about coronaviruses for over 60 years, how they work, the genes in them, etc.) and they have whopping big proteins on the surface that don't change a whole lot with time. We also know have molecular biology technology developed in the past few years that makes it possible to rapidly sequence RNA, synthesize RNA, and deliver RNA to cells to express it. So, it took about 3 days to sequence the virus, and a few weeks, to synthesize the RNA message that could teach cells to produce the surface protein of the virus and teach the immune system to recognize it. The whole process could technically be done in a week -- the parts that slow it down are: scaling up production, setting up quality control to make sure it's consistent without contamination, and all the safety testing and process to review safety data, get permission to proceed, etc.
Asylumdown t1_j5vresc wrote
That’s not necessarily why HIV is hard to make a vaccine for. People can be infected for years without it damaging their immune system to the point where it can no longer mount a defense against HIV. People DO develop robust immune responses to HIV, that’s actually what an HIV+ diagnosis is - positive for HIV antibodies.
Part of the problem is what we think we’re talking about when we say “immune”. Becoming vaccine-immune to something doesn’t mean that none of your cells will ever become infected by that virus, it means that your body will recognize the signs of infection on your cell surfaces and destroy the infected cells before the infection progresses to the point where you’re acutely sick.
The problem is that HIV is incredibly efficient at evading exactly that immune response. It’s not a regular RNA virus that hijacks the entire cell and rapidly reproduces until the cells explode. It’s a retrovirus that transcribes itself right in to your DNA and slowly (relative to something like influenza) buds off new viral particles without immediately killing the cell it’s infected. Your body could be chock-a-block full of HIV antibodies, but if even one viral particle gets through and infects a CD4 cell, there is a high chance it can churn out enough viral particles to produce systemic infection before your immune system notices there’s something amiss with that one specific cell. This is what happens with any infection you have vaccine immunity to - some number of cells will become infected and produce more virus, but in HIV’s case, one of the first places those newly produced viral particles will go are your latent or resting immune cells. These cells won’t immediately begin transcribing any new virus and and HIV writes itself right in to their DNA. It effectively hides itself from the immune system by writing itself in to the DNA of your immune system. That’s also why treatment has to be lifelong. Those latent or resting immune cells can wake up at any time and start the whole thing over again. Some naturally do every day in every human body through the normal functioning of your immune system.
It’s why drugs like PrEP work and vaccines don’t. PrEP, when taken correctly, stops HIV from reproducing at all. So even though some random CD4 cell near the exposure site might become infected, it can never make any new HIV particles and that cell will eventually be cleared from the body through natural processes. It can’t progress to a latent reservoir of infected cells that can permanently hide from the immune system. It’s also why PEP (post exposure prophylaxis) can work, if taken early enough.
tforss t1_j5xwwnv wrote
HIV is hard to make a vaccine for because without consistent treatment there is no way for the body to fully eradicate it, and it will only progressively get worse. Even with medication, it only suppresses the virus. The body is unable to replicate this protection on its own without the assistance of medication. If a vaccine existed that could stimulate the immune system to produce this defence naturally, it wouldn't have to rely on medication, at least not entirely.
So yes its hard to make a vaccine for something not fully understood and why the immune system cant develop any form of natural resistance. No matter how long someone has been diagnosed as positive, their immune system has no ability to ever learn to protect itself from this.
Asylumdown t1_j60g0tf wrote
That’s not entirely true. The body does learn to protect itself and it does mount an antibody response and does attack HIV infected cells.
But HIV is one of only three retroviruses that we know about that infect humans and cause disease. The body can’t fully clear any of them. Retroviruses aren’t the only viruses our bodies can’t clear, but the mechanism for why is different from other acute viral infections that hijack your cellular machinery to rapidly print out millions of copies of themselves, killing the host cell in the process. Retroviruses write themselves right in to your DNA and can leave zero trace of themselves on the surface of the cell they’ve infected for weeks, months, or years. Until your own DNA starts transcribing those viral proteins, it’s virtually invisible to your immune system. Once you’re systemically infected with any of the three human retroviruses, some (large) number of cells somewhere in your body will have the instructions to make more of that virus baked in to their biological operating system for the rest of your life. It’s why vaccines don’t work (at least on HIV). Vaccines don’t stop cells from becoming infected. They help your body kill off the infected cells before the infection gets out of control. But with HIV, really any level of active viral replication is “out of control” because it goes straight to places your immune system will never be able to see and immediately hides in cells you will have for the rest of your life.
It sets up a war of attrition that the body has no mechanism to win. With HIV that war involves the very cells the body needs to fight off viral infections, so over time the immune system slowly fails. With the other two retroviruses we can get, they can eventually cause lymphoma.
That said, the medications for HIV are incredibly effective both as a treatment and as a preventative. They completely shut down viral replication. There’s ones that stop HIV from entering a cell at all, one’s that stop it from transcribing itself from RNA in to DNA, one’s that stop it from integrating with your DNA, and ones that stop it from assembling new, functional viral particles. They can’t write it out of the DNA of already infected cells - again, some of which you’ll have for the rest of your life - but they can stop any new cells from becoming infected and keep viable viral particles out of the blood and sexual fluids.
[deleted] t1_j5vc8sn wrote
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[deleted] t1_j5vcjf7 wrote
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Still-No-Astronaut t1_j5vkf4g wrote
>It doesn't seem to prevent people from getting sick which is what we were told it would do.
This statement is just incorrect. If you were under the impression that vaccines prevent people from becoming infected, you were mistaken. They prevent hospitalization and death. That has been proven in randomized controlled trials.
Alexis_J_M t1_j5vlh5v wrote
The COVID vaccines have a dramatic difference in the number of people who die, the number of people who get sick enough to go to the hospital, the number of people who are sick long term. That's basic statistics, well understood.
The people dropping dead and having heart problems? Those are statistically insignificant. It's a tragedy when someone drops dead 3 days after their COVID vaccine, but it's not statistically much more likely than people dropping dead for other reasons. Acetaminophen kills more people every year by a wide margin, but you don't hear people talking about banning that.
"Herd Immunity"? The virus is out-mutating that. Just ask all the people who have gotten COVID 3 or 4 times. Just ask the countries that tried that as a national strategy.
It's truly disheartening just how politicized the reaction to COVID-19 has been.
[deleted] t1_j5vm8pi wrote
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FellowConspirator t1_j5vmicp wrote
Unfortunately, a lot of people have the same confusion, and it's because politically minded people have fostered it. The science and medicine involved aren't so complicated that a layman couldn't grasp it, but unless you seek out the information or rely on expertise and reliable sources, you'd end up where you find yourself.
Ask yourself: is there an empirical way to determine the efficacy of a vaccine? How do vaccines work / what is the mechanism by which they act? Who has this information / where can I find it? Are there populations that are more clinically at risk from infection? What is the mechanism of that? Why do I not know the answer to these questions? Where would I go to find studies and experts in the field?
All of your questions have been asked and have clinical and scientific answers that an unambiguous and with exquisite detail. It's only political if you ignore the science and listen to the pundits and politicians.
ggiesen t1_j5wpzs8 wrote
We know because we have randomized, double-blind studies and millions upon millions of doses and millions upon millions of infections. We know statistically you're far less likely to end up in the hospital or die from Covid if you're vaccinated, and have millions of examples to prove this out.
That doesn't mean you will never get sick or die from Covid if you're vaccinated, just that you're far less likely to, and as such, the vaccine works. All of these are well understood if you don't bury your head in the sand or fill it with extremist garbage.
Sure, perhaps we've come to expect too much from vaccines, like with the efficacy of things like the polio vaccine which has effectively eradicated the disease. We were all hoping for a silver bullet that can end the pandemic. But that doesn't mean the vaccine doesn't work or that we would be better off without it.
throaway-90210 t1_j5wvipc wrote
A few things:
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We were never guaranteed it would prevent transmission, the original trials were against symptomatic disease. Transmission data was gathered in real time as vaccines were given, and it's an imperfect science anyway. Many vaccines don't stop transmission including the inactivated polio vaccine.
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We will always be a step in behind in vaccine updates because of the regulatory process, we updated vaccines to BA.5 and now XBB.1.5 is dominant. It's going to be this way.
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It's not an argument, it's a fact it has reduced burden all you have to do is compare hospitalization rates for those vaccines and those not. Unfortunately many people don't understand base rate fallacy.
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The increased risk of myocarditis has been acknowledged by every major health body. You know what else causes myocarditis, viruses. The flu can cause it. We know COVID-19 causes it.
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The virus will continue to mutate away from immune responses. Herd immunity is definitely not here in the way many people use the term.
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