Vaccination of calves in the face of maternal antibodies (IFOMA) often does not result in seroconversion as maternally derived immunity interferes with the activation of adequate antibody responses to vaccination; however, it can prime T and B cell memory responses that protect calves against clinical disease when maternal immunity has decayed. The activation of B and T cell memory responses in calves vaccinated IFOMA varies and is affected by several factors, including age, level of maternal immunity, type of vaccine, and route of administration. These factors influence the adequate priming of humoral and cell mediated immune responses and the outcome of vaccination. The failure to adequately prime immune memory after vaccination IFOMA could result in lack of clinical protection and increased risk of viremia and/or virus shedding.