Comparative Transcriptomic Analysis of Innate Immune Responses to Foot-and-Mouth Disease Vaccine Antigens in Indigenous and Crossbred Nigerian Cattle

Foot-and-mouth disease vaccination remains the cornerstone of control strategy in Nigerian cattle, but vaccine efficacy is inconsistent across herds and breeds, with indigenous Zebu breeds frequently showing suboptimal seroconversion compared with Friesian crossbreds despite identical vaccination protocols. The immunological and transcriptomic basis for this breed-dependent vaccine responsiveness has not been investigated in Nigerian cattle populations. This study conducted a comparative transcriptomic analysis of innate immune responses to foot-and-mouth disease virus antigen in dendritic cells and peripheral blood mononuclear cells from White Fulani, N'Dama, and Friesian crossbred cattle from Kaduna, Edo, and Ogun states respectively. Forty-five cattle, 15 per breed, were vaccinated with the standard trivalent O, A, and SAT2 inactivated vaccine. Blood was collected pre-vaccination and at 24, 48, and 72 hours post-vaccination for transcriptomics and immunological phenotyping. Peripheral blood mononuclear cells were isolated and subjected to bulk RNA sequencing with strand-specific library preparation and Illumina NextSeq 500 sequencing at 25 million reads per sample. Dendritic cells were cultured and stimulated with killed FMDV antigen for ex vivo transcriptomic comparison. Differential gene expression, gene ontology enrichment, and weighted gene co-expression network analysis were applied. N'Dama cattle demonstrated significantly stronger innate immune transcriptomic responses at 24 hours, characterised by higher induction of type I interferon response genes, pattern recognition receptors, and antigen presentation pathway genes compared with White Fulani and Friesian crossbreds. Friesian crossbreds showed the most pronounced adaptive pre-cursor activation signature at 72 hours. Gene networks associated with interferon stimulated gene induction correlated positively with subsequent antibody titres at day 28. These breed-specific innate immune transcriptomic signatures provide a mechanistic basis for differential vaccine responsiveness and inform breed-tailored vaccination schedule optimisation for foot-and-mouth disease control in Nigeria. Keywords: foot-and-mouth disease, vaccine immunology, transcriptomics, innate immunity, cattle breeds.