Self-assembling fowl adenovirus virus-like particles: Mechanistic insights and emerging strategies for vaccine development

Abstract

Background and Aim: Fowl adenoviruses (FAdVs) are important pathogens of poultry and are associated with economically significant diseases, including inclusion body hepatitis, hepatitis-hydropericardium syndrome, and gizzard erosion. The substantial genetic and antigenic diversity among FAdV species and serotypes can limit cross-protection provided by conventional vaccines, emphasizing the need for safer and more adaptable vaccination strategies. Virus-like particles (VLPs) offer a promising approach because they mimic the structural organization of native virions while lacking viral genetic material. This review summarizes current knowledge of FAdV capsid architecture and the molecular mechanisms governing self-assembly and examines their relevance to VLP-based vaccine development. Particular attention is given to the structural and immunological functions of hexon, fiber, and penton base proteins, including their roles in capsid formation, host-cell interactions, antigenicity, and protective immunity. The review also evaluates current strategies for recombinant expression and VLP production, including bacterial, insect cell–baculovirus, and mammalian expression systems, together with approaches for improving protein folding, assembly efficiency, yield, purification, and stability. Available experimental evidence indicates that FAdV capsid proteins can induce humoral and cellular immune responses and that recombinant, chimeric, and multivalent antigen designs may broaden protection against antigenically diverse serotypes. However, evidence specifically demonstrating the performance of fully assembled FAdV-derived VLP vaccines remains limited, with many studies focusing on individual recombinant capsid proteins or early experimental vaccine candidates. Major barriers to practical application include efficient particle assembly, scalable manufacturing, structural stability, preservation of immunogenicity, production cost, and validation of cross-protective efficacy under field conditions. Advances in structural analysis, computational modeling, antigen engineering, expression platform optimization, and formulation strategies may facilitate the rational development of more stable and broadly protective VLP vaccines. Overall, FAdV VLP technology represents a promising platform for next-generation poultry vaccines, but further mechanistic studies, standardized characterization, controlled challenge experiments, and large-scale field validation are required before widespread commercial application. Keywords: capsid assembly, fowl adenovirus, hexon protein, poultry vaccines, recombinant vaccines, self-assembly, vaccine development, virus-like particles.