Enteral immunization with live bacteria reprograms innate immune cells and protects neonatal foals from pneumonia

Using a horse foal model, we show that enteral immunization of newborn foals with Rhodococcus equi overcomes neonatal vaccination challenges by reprogramming innate immune responses, inducing R. equi-specific adaptive humoral and cell-mediated immune responses and protecting foals against experimental pneumonia challenge. Foals were immunized twice via gavage of R. equi (immunized group) or saline (control group) at ages 1 and 3 days. At age 28 days, all foals were challenged intrabronchially with R. equi. Post-challenge, all 5 immunized foals remained healthy, whereas 67% (4/6) of control foals developed clinical pneumonia. Immunized foals exhibit changes in the epigenetic profile of blood monocytes, > 1,000 differentially-expressed genes in neutrophils, higher concentrations of R. equi-specific IgG₁ and IgG_4/7, and a higher number of IFN-γ producing lymphocytes in response to R. equi stimulation indicating T helper type 1 response compared to control foals. Together, our data indicate that early life exposure to R. equi in the gastrointestinal tract can modulate innate immune responses, generate specific antibodies and cell-mediated immunity, and protect against pneumonia.