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Asylumdown t1_j5vresc wrote

Reply to comment by FellowConspirator in What determines whether we can create a vaccine for an illness or not? by ShelfordPrefect

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.

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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.

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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.

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