Current challenges emerging strategies and future directions in vaccine development for haemorrhagic septicemia

Abstract Haemorrhagic septicemia (HS), caused by Pasteurella multocida serotypes B:2 and E:2, remains a major infectious disease of cattle and buffalo in endemic regions of Asia and Africa and has increasingly been recognized as a threat to susceptible wildlife. Despite decades of vaccination, recurrent outbreaks continue, highlighting important limitations in current immunization strategies. This review critically examines the evolution of HS vaccines from conventional inactivated formulations, including bacterins, alum-precipitated, aluminium hydroxide gel, and oil-adjuvanted vaccines, to emerging next-generation approaches. While traditional vaccines have reduced mortality, their effectiveness is constrained by a short duration of immunity, the need for booster doses, post-vaccination reactions, and limited cross-serovar protection. Advances in molecular vaccinology have enabled the exploration of alternative strategies. These include autogenous preparations, genetically engineered mutants, recombinant subunit and acellular vaccines, bacterial ghosts, anti-idiotype approaches, and novel adjuvant systems. Particular attention is given to antigen-focused design targeting outer membrane proteins, capsule components, lipopolysaccharides, and virulence-associated metabolic pathways. The review also discusses progress in vaccine delivery technologies, especially intranasal and intradermal immunization, which may enhance mucosal immunity, improve the quality of immune reposnse, and facilitate mass vaccination. Nevertheless, major translational challenges remain, including the lack of defined correlates of protection, insufficient validation in target species, and constraints related to stability and scalability. Addressing these gaps is essential for developing durable and broadly protective HS vaccines for both livestock and wildlife.