With millions more Americans getting vaccinated every day, some have complained about fever, fatigue and other ailments they weren't expecting. Though vaccines are still very effective even without side effects, experiencing side effects are short-lived and are actually proof that your immune system is working the way it's supposed to. BIO5 associate director and UArizona EEB department head Dr. Michael Worobey says, with the first dose, you are having to generate an immune response from the ground up. The body produces antibodies, but also begins generating B cells to make targeted antibodies. The second time you give a person the shot, those cells are sitting around like a clone army and can immediately start producing a very big immune response.