When a new mutation within the SARS-CoV-2 spike protein receptor binding domain (RBD) emerges that a particular antibody can no longer neutralyze, it is often called an escape variant. With the rapid identification of these new variants within the infected population, and also in lab-generated versions of the spike protein, an exhaustive escape variant matrix has begun to take shape. The good news is that as long as the actual antibody responses of vaccinated individuals are tested and verified, the individual’s response to different variants can, at least in theory, be predicted. The full response of our innate and adaptive immune systems to a fragment of a key viral entry protein will never be exactly the same as the response to natural infection with whole live virus, but in terms of generating similar antibodies that target key epitopes, it is often good enough.