Salmonellosis is one of the leading food-borne illnesses among humans worldwide. Salmonella contamination of eggs and meat is attributed as the major source of infection in humans. There are over 200 Salmonella serotypes that can colonize the GI tract of poultry. Vaccination has emerged as a promising control strategy against bacteria in the poultry sector. Furthermore, killed Salmonella vaccines are preferred over live vaccines due to biosecurity reasons. At present, killed vaccines are serovar-specific and induce robust humoral-immunity. However, for the efficient eradication of Salmonella, a killed vaccine that can confer cross protection against major Salmonella serovars present in poultry farms, along with the induction of strong cell-mediated immunity is needed. This study aims to investigate the efficacy and safety of two killed Salmonella bacterin vaccines in layers. In both experiments, the vaccines increased (P < 0.05) the Salmonella-specific serum IgY both pre- and post-challenge with Salmonella enterica ser. Enteritidis.