Immunogenomics Approaches to Studying Antibody Repertoires and Vaccine Responses in Ruminants

Ruminant species are vital for agriculture, ecosystems, and conservation and remain vulnerable to infectious and zoonotic diseases. Advances in genome sequencing and genomics now enable high-resolution analysis of immunoglobulin (IG) loci and antibody repertoires uncovering extensive germline diversity, structural variation, and lineage-specific adaptations, such as ultralong cysteine-rich Abs in cattle. This review summarizes current knowledge of ruminant IG locus organization and repertoire generation and discusses the evolutionary origins of ultralong Abs. It also examines the challenges highly repetitive IG loci pose for assembly, annotation, and nomenclature and highlights emerging solutions. Finally, it describes genomic approaches for linking immune genotypes to phenotypes that create promise for improving ruminant health.