[alsocasey]

In the case of vaccines specifically, there is just a surprising amount of things we still don't understand.

Vaccination is positively ancient technology (Smallpox circa 1796), but it is still difficult to say why e.g., some vaccines are broadly effective at producing immunity and some aren't (and what the factors at play are in the recipients), or why we can produce successful vaccines to some diseases and not others.

A specific example: the efficacy of BCG vaccination (tuberculosis) varies by manufacturer and the reasons for why that is are still unclear.

There are a number of large NIH-funded initiatives that aim at understanding the complex cellular and molecular interactions that result in immunity as a result of vaccination under the Human Immunology Project Consortium (a bunch of high profile papers in Cell, etc. over the past few years).