breakthrough infection breakthrough infection a breakthrough infection is a case of illness in which a vaccinated individual becomes infected with the illness, because the vaccine has failed to provide complete immunity against the pathogen (currently only viruses). breakthrough infections have been identified in individuals immunized against a variety of diseases including mumps, varicella (chickenpox), influenza, and covid-19. the characteristics of the breakthrough infection are dependent on the virus itself. often, infection of the vaccinated individual results in milder symptoms and shorter duration than if the infection were contracted naturally.