West Nile Virus (WNV) belongs to the orthoflavivirus genus and is part of the Flaviviridae family, which includes the Japanese encephalitis virus, Dengue virus, Zika virus, and yellow fever virus. WNV circulates among birds and mosquitoes, posing infection risks to humans and mammals. The significant rise in WNV’s geographic spread and infection rates over the past five decades has prompted urgent public health concerns, driving the need for accelerated vaccine research. The development of a vaccine for WNV infection presents several challenges, primarily due to the virus’s complex biology, the risk of cross-reactivity with other flaviviruses, safety concerns such as antibody-dependent enhancement (ADE), and the economic and logistical hurdles in vaccine production. Despite significant research efforts, no human vaccine has been approved, although several candidates are in various stages of development. The current review offers a comprehensive summary of the latest progress and the concomitant challenges in the development of vaccines. It also discusses the role of host–pathogen interaction, host immunity, viral immune evasion, and disease pathogenesis in facilitating the advancement of vaccines.

West Nile Virus (WNV) belongs to the orthoflavivirus genus and is part of the Flaviviridae family, which includes the Japanese encephalitis virus, Dengue virus, Zika virus, and yellow fever virus. WNV circulates among birds and mosquitoes, posing infection risks to humans and mammals. The significant rise in WNV's geographic spread and infection rates over the past five decades has prompted urgent public health concerns, driving the need for accelerated vaccine research. The development of a vaccine for WNV infection presents several challenges, primarily due to the virus's complex biology, the risk of cross-reactivity with other flaviviruses, safety concerns such as Antibody-dependent enhancement (ADE), and the economic and logistical hurdles in vaccine production. Despite significant research efforts, no human vaccine has been approved, although several candidates are in various stages of development. The current review offers a comprehensive summary of the latest progress and the concomitant challenges in the development of vaccines. It also discusses the role of host-pathogen interaction, host immunity, viral immune evasion, and disease pathogenesis in facilitating the advancement of vaccines.

The rapid emergence of antimicrobial resistance (AMR) has become a significant challenge in both human and veterinary medicine, largely driven by the misuse and overuse of antibiotics, including inappropriate cross-species dosage extrapolation. Empirical antimicrobial dosing can result in subtherapeutic exposure, disruption of the microbial ecosystem, and increased selective pressure, thereby accelerating the emergence and dissemination of resistant bacteria. Maintaining microecological homeostasis, particularly the stability of the commensal microbiota, is increasingly recognized as essential for limiting the development of resistance and preserving host health. Although interspecies scaling, Monte Carlo simulations, population pharmacokinetics (PK), and physiologically based PK models have been used to predict dosage regimens, their complexity and extensive data requirements restrict routine application in veterinary practice. In this context, PK/pharmacodynamic (PD) modeling provides a practical and scientifically robust framework for rational antimicrobial therapy. By integrating drug concentration–time profiles with antimicrobial effects, PK/PD-guided approaches enable species-specific dose optimization that improves therapeutic efficacy, minimizes ecological disruption, and reduces AMR selection pressure. This review highlights the application of modern PK/PD strategies in veterinary medicine as an essential tool for sustainable antimicrobial stewardship, AMR mitigation, and preservation of microbial ecosystem stability.