Gyeong-Seo Park, Minsung Park, Somin Lee, Chonghan Kim, Byoung Joo Seo
Bovine neonatal diarrhea (BND) is a leading cause of morbidity and mortality in pre-weaned calves. Commercial maternal vaccines targeting bovine rotavirus (BRV), bovine coronavirus (BCoV), and enterotoxigenic Escherichia coli (ETEC) have been available for decades, yet field outbreaks continue in vaccinated herds. This review examined peer-reviewed literature published between January 2019 and March 2026, identified through a structured PubMed search supplemented by reference-list screening. For BRV, a field strain sharing its VP7 genotype with a vaccine component was not neutralized by vaccine-induced antiserum, indicating that genotype concordance does not predict serologic coverage. For BCoV, hemagglutinin-esterase variation and regional lineage divergence indicate surface-protein evolution, although data linking these changes to reduced efficacy are not available. For ETEC, adhesin diversity and antimicrobial resistance affect both vaccination strategy and case management. Maternal vaccination retains biological value, but field performance is constrained by colostral variability, incomplete passive transfer, and product-to-product immunogenic differences. For all three pathogens, antigenic divergence from vaccine strains is located at individual epitopes, receptor-binding domains, or adhesins rather than at the level of whole-pathogen identity. Subunit and multi-epitope antigen designs, for which proof-of-concept constructs have been reported, operate at this level, and their selection requires characterization of candidate antigens for efficacy, diversity, polymorphism, and cross-protective breadth. Such antigen improvements address the pathogen-side gap but not the passive-transfer and mucosal constraints. Functional surveillance to guide antigen updating, field trials that measure passive-transfer efficiency, and adjunctive strategies are identified as priorities for BND control.