I worked in a lab studying malaria vaccinology. There a bunch of difficulties with trying to develop a vaccine that I think are well covered here. I also learned some about the history of malaria research.

1. It is a pain in the ass to study malaria. You need to have an insectary to grow mosquitoes (through their muktiple life stages, of course) and have them feed on infected mice just to passage the parasite. This isn't like viruses where you just throw then into vero cells or bacteria that will grow in LB overnight. Parasites require dedication. This kind of operation costs a university hundreds of thousands of dollars to get up and running, and there are not too many places in the US that have robust malaria research because of it. UW and the Boston area are two that I know with good malaria research centers.

2. The lifecycle of malaria is very difficult to make a vaccine against. This is described in the article. Essentially, you go from mosquito -> skin parasite (few hr) -> liver parasite (7d also no symptoms) -> blood parasite -> mosquito. Also, the prevailing idea is that the amplification during the liver stage through red blood cell stage is so great that once the blood stage is established, it's game over. You are going to get sick as a dog. So you have a few options: target the sporozoite in the skin and blood within a couple hours, or target the liver stage where the parasite is essentially dormant and is nearly impossible to find. (My research was finding antigens in the liver stage, there are very few and they don't produce very good immune responses with standard vaccination techniques). You have to remember that for the immune system to work, you need to see the signs of the pathogen, then give yourself 5 days at the absolute minimum to expand your T cells to eradicate the pathogen. And oftentimes we're talking less than 10 infected cells in the entire liver, which is a huge organ with famously tortuous circulation. So good luck on the liver stage.

All this ignoring the fact thatthe mouse model of malaria goes through the liver stage in just 4 days, which doesn't allow expansion of T cells for killing the bug. So even if we found the perfect antigen to vaccinate against, we don't have good models in mice to actually evaluate how effective a vaccine would be because of the differing biology of the model. There are some people who reconstitute human livers in mice so they can use the 7 day parasite, but those mice are pretty messed up and very expensive. And handling mosquitoes that carry human malaria is much more annoying than the mouse malaria. Still a very interesting and compelling model for research.

3. Interest in protein based vaccinations. There was a study long ago that used irradiated parasites that protected people from subsequent infections. The problem is that it took a LOT of parasites, and 5 doses of the vaccine. This strategy is similar to the inactivated virus kind of vaccinations that we all likely have received. But these parasites needed to be injected IV, 5 doses, and the parasites need to be kept at -80C until injection time. That might work for a vaccine delivered in a metropolitan area, but good luck finding -80 freezers in an African village. Around this time, researchers got interested in protein based vaccines, like the pertussis vaccine. So people went looking for a protein that was highly immunogenic, and they landed on CSP, which the article describes nicely. However, this again is mostly expressed on the skin parasite so you have just hours to recognize that protein and kill the parasite. Much less than the ideal 5-7 days.

4. Financial incentives are of course a problem. Though many would argue that financial incentives are bad for vaccine development in general because they prevent any disease from occuring, so you are eliminating your market if they work well.

So where does this leave us? If we keep thinking of vaccines as we typically do, we are going to just create marginally better versions of RTS,S, which isn't great. In my opinion, the most likely way to vaccinate against malaria is transmission blocking vaccines, which would eliminate only the blood stage parasites that need to be picked up by a feeding mosquito to allow replication in the mosquito foregut. But this kind of vaccine wouldn't prevent the individual from getting sick. It would take a replication cycle of a fully vaccinated population to take it out, which is a very unappealing proposition.