Current strategies and challenges in vaccine platforms for Newcastle Disease Virus

Abstract Newcastle disease virus (NDV) remains one of the most economically devastating pathogens affecting poultry production. Despite decades of vaccination efforts, NDV continues to circulate and remain endemic across Asia, Africa, and the Middle East, posing persistent threats to food security, rural livelihoods, and international trade. This review comprehensively examines the current landscape of NDV vaccine platforms, their immunological mechanisms, and the multifaceted challenges limiting their efficacy. We critically evaluated conventional platforms, including lentogenic live attenuated vaccines and oil-adjuvanted inactivated formulations, highlighting their contributions to disease control while addressing their inherent limitations including cold-chain dependence, maternal antibody interference, incomplete cross-protection against heterologous genotypes, and the absence of differentiating infected from vaccinated animals (DIVA) capability. We then examined next-generation approaches, including recombinant vector platforms, virus-like particles, DNA and mRNA vaccines, and AI/ML-informed antigen design, assessing each against its actual stage of development, from vaccines already in commercial use to platforms that remain preclinical or theoretical, rather than treating design capability as equivalent to field-ready deployment. Finally, we addressed regulatory, manufacturing, and logistical barriers to vaccine deployment in low-resource settings, including a dedicated feasibility assessment and platform-comparison table for smallholder-dominated, endemic regions. Integrating these technological advances with robust surveillance, biosecurity, and supportive policies will be essential for achieving sustainable NDV control and advancing toward eradication.