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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 mutat
by dist-epoch 3mo ago
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.
- mrguyorama 3mo agoHIV isn't the only virus that generates decoys to trick antibody development, so having techniques that bypass that decoy strategy is very useful.
- Melatonic 3mo agoWhat else does this?
- greazy 3mo agoI think all viruses do to some extent. We refer to them as DIPs https://en.wikipedia.org/wiki/Defective_interfering_particle https://en.wikipedia.org/wiki/Defective_interfering_particle List includes RSV, flu, sc2 and of course hiv
- M95D 3mo agoAll single-stranded RNA viruses do that. But it's being done to them is the more correct term. A single strand of RNA is unstable and prone to mutations due to enviromental factors.
- calf 3mo agoWhat's the risk of collateral damage or autoimmune issues from this kind of process, it sounds more difficult to evaluate for safety because it is more complicated.
- dist-epoch 3mo agoIt's still the body doing the work, the antibodies will still be tested for self-attack in the regular ways, so there shouldn't be any impact. But immunity is super-complicated, so who knows...
- wwweston 3mo agoA fascinating everyday arms race I had no idea was playing out around me.
- pazimzadeh 3mo agoHere’s a fun read on that arms race The acquired immune system: a vantage from beneath https://pubmed.ncbi.nlm.nih.gov/15539148/ 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
- Fire-Dragon-DoL 3mo agoEverything I hear is about bacterias though. I wish we found more about viruses.
- bongoman37 3mo agoBacteria is plural, bacterium is singular.
- pazimzadeh 3mo agoviruses and transposons are a major source of creativity in life. the adaptive immune system of jawed vertebrates like us, which defends against viruses, only exists because the RAG transposon inserted itself into the gonads of our fish ancestors 500 million years ago Origin of immunoglobulins and T cell receptors: A candidate gene for invasion by the RAG transposon https://pubmed.ncbi.nlm.nih.gov/40614193/ https://pubmed.ncbi.nlm.nih.gov/40614193/
- mjevans 3mo agoThis sounds a lot like the firewall technique of port knocking. Poke this thing to enable a ruleset, then another thing in that state for a different ruleset, etc.