not-yet-known not-yet-known not-yet-known unknown 2.4 Vaccination Vaccination options consist of inactivated, live, and subunit vaccines. Current research is moving from inactivated vaccines to exploring live-attenuated and recombinant vaccines for chickens.14,15 Various tested vaccines, such as outer membrane vesicles (OMVs), bacterial ghost vaccines, recombinant vaccines, vaccines with ExPEC antigens, and Salmonella-delivered vaccines containing APEC antigens, have proven effective in lowering mortality rates, minimizing lesions, and reducing bacterial load, while also eliciting antibody responses in chickens. 2 Despite the effectiveness of several vaccine candidates in experimental trials, only two vaccines are commercially accessible for chickens: live-attenuated PoulvacĀ® and inactivated NobilisĀ®. However, these vaccines fall short in offering protection against the diverse range of APEC infections. The ideal solution would be a vaccine that offers cross-protection against various serotypes and can be administered through mass vaccination methods, such as oral or spray applications.14 Discovering the shared virulence and pathogenesis mechanisms among APEC serotypes can help in creating broad-spectrum vaccines. For example, vaccines that use outer membrane iron receptors have been effective against UPEC in mice, while a tetravalent conjugate vaccine using UPEC O antigens provides broad protection. Focusing on new virulence factors, such as the type VI secretion system and quorum sensing, could lead to the development of more effective vaccine candidates.2,15-18 A major challenge in developing recombinant vaccines is pinpointing highly immunogenic genes or effective immunopotentiators. Administering CpG oligodeoxynucleotides subcutaneously or intramuscularly can boost the innate immune response and reduce cellulite lesions, thanks to the CpG motifs found in bacterial DNA sequences.4,5 Vaccines are often less effective against diverse field serogroups, which limits their protection against colibacillosis, even though they can be effective against homologous strains. In contrast, alternative therapies, especially virulence inhibitors, offer a promising solution with a reduced likelihood of resistance and the potential for long-term control.1,2,19