Animal Models for Swine Influenza Virus Research: Pathology, Viral Dynamics, and Immune Responses.

Abstract

Swine influenza virus (SIV) continues to evolve and possesses notable zoonotic potential, making it an important respiratory pathogen of concern for both the global swine industry and public health. Owing to antigenic drift, genetic reassortment, and regional lineage diversity, vaccine efficacy against SIV shows marked variability across different epidemiological contexts. Therefore, establishing appropriate animal models to dissect its pathogenic mechanisms, transmission characteristics, and immune response patterns is of critical importance. This review systematically summarises the animal models commonly used in SIV research, including mice, ferrets, guinea pigs, pigs, and non-human primates, and provides an integrated analysis across three core dimensions: pathological manifestations, viral replication kinetics, and immune architecture. The evidence indicates that substantial inter-model differences exist in pulmonary lesion distribution, transmission efficiency, mucosal immune development, and cellular immune complexity, which in turn define their functional roles in mechanistic studies, transmission research, and vaccine evaluation. Building on this framework, this review further emphasises the value of a tiered, multi-model strategy in SIV research. In vitro systems and mouse models are well suited for early mechanistic exploration and preliminary vaccine screening; ferret and guinea pig models facilitate the evaluation of transmission dynamics; and the pig model, as the natural host system, remains the critical platform for confirming protective efficacy, identifying potential immunopathological risks, and assessing translational relevance. Importantly, the potential occurrence of vaccine-associated enhanced respiratory disease under antigen-mismatched conditions highlights the need to evaluate both protective performance and immunological safety during vaccine development. Overall, rational integration of evidence across multiple models, anchored to the natural host, will improve the predictability and translational reliability of SIV vaccine research.