IntroductionThe objectives of this study were to evaluate the impacts of two modified-live virus (MLV) vaccination protocols and respiratory disease (BRD) occurrence on the microbial community composition of the nasopharynx in feedlot cattle.MethodsThe treatment groups included in this randomized controlled trial included: 1) no viral respiratory vaccination (CON), 2) intranasal, trivalent, MLV respiratory vaccine in addition to a parenteral BVDV type I and II vaccine (INT), and 3) parenteral, pentavalent, MLV respiratory vaccination against the same agents (INJ). Calves (n= 525) arrived in 5 truckload blocks and were stratified by body weight, sex, and presence of a pre-existing identification ear-tag. A total of 600 nasal swab samples were selected for DNA extraction and subsequent 16S rRNA gene sequencing to characterize the microbiome of the upper respiratory tract. Nasal swabs collected on d 28 from healthy cattle were used to evaluate the impact of vaccination on upper respiratory tract (URT) microbial communities.ResultsFirmicutes were less abundant in INT calves (n= 114;P< 0.05) and this difference was attributed to decreased relative abundance (RA) ofMycoplasma spp. (P= 0.04).MannheimiaandPasteurellahad lower RA in INT (P< 0.05). The microbiome in healthy animals on d 28 had increased Proteobacteria (largelyMoraxellaspp.) and decreased Firmicutes (comprised almost exclusively ofMycoplasma spp.) compared to animals that were treated for or died from BRD (P< 0.05). Cattle that died had a greater RA ofMycoplasma spp. in their respiratory microbiome on d 0 (P< 0.02). Richness was similar on d 0 and 28, but diversity increased for all animals on d 28 (P>0.05).