The most interesting point of the article for me is that this vaccine appears to be a series of shots which act as a curriculum for the immune system. Each one slightly different and targeting a different stage of B-cell development. I've never thought of vaccine series working like that, so it was a new and impressive idea.

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.