Kahn, S. K. | bioRxiv Science

bioRxiv2024

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

Neonatal immunization faces several challenges due to the immune systems immaturity and naivety, and several vaccines that induce adequate immune response in adults fail to protect neonates. Using a horse foal model, we show that enteral administration of Rhodococcus equi to newborn foals 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. Immunized foals exhibit changes in the epigenetic profile of blood monocytes, >1,000 differentially-expressed genes in neutrophils, and higher levels of R. equi-specific IgG1, IgG4/7, and T helper type 1 response. Together, our data indicate that early life exposure to R. equi in the gastrointestinal tract can induce enhanced innate immune responses, which may facilitate the development of adaptive immune responses and protect neonates against pneumonia through a previously unappreciated gut-lung axis. TeaserEnteral immunization of newborn foals with live bacteria enhances systemic innate immune responses through the gut-lung axis.

immunology↗

bioRxiv2021

Antibody Activities in Hyperimmune Plasma Against the Rhodococcus equi Virulence -Associated Protein A or Poly-N-Acetyl Glucosamine are Associated with Protection of Foals Against Rhodococcal Pneumonia

The efficacy of transfusion with hyperimmune plasma (HIP) for preventing pneumonia caused by Rhodococcus equi remains ill-defined. Quarter Horse foals at 2 large breeding farms were randomly assigned to be transfused with 2 L of HIP from adult donors hyperimmunized either with R. equi (RE HIP) or a conjugate vaccine eliciting antibody to the surface polysaccharide {beta}-1[->]6-poly-N-acetyl glucosamine (PNAG HIP) within 24 hours of birth. Antibody activities against PNAG and the rhodococcal virulence-associated protein A (VapA), and to deposition of complement component 1q (C1q) onto PNAG were determined by ELISA, and then associated with either clinical pneumonia at Farm A (n=119) or subclinical pneumonia at Farm B (n=114). Data were analyzed using multivariable logistic regression. Among RE HIP-transfused foals, the odds of pneumonia were approximately 6-fold higher (P = 0.0005) among foals with VapA antibody activity [≤] the population median. Among PNAG HIP-transfused foals, the odds of pneumonia were approximately 3-fold (P = 0.0347) and 11-fold (P = 0.0034) higher for foals with antibody activities [≤] the population median for PNAG or C1q deposition, respectively. Results indicated that levels of activity of antibodies against R. equi antigens are correlates of protection against both subclinical and clinical R. equi pneumonia in field settings. Among PNAG HIP-transfused foals, activity of antibodies with C1q deposition (an indicator of functional antibodies) were a stronger predictor of protection than was PNAG antibody activity alone. Collectively, these findings suggest that the amount and activity of antibodies in HIP (i.e., plasma volume and/or antibody activity) is positively associated with protection against R. equi pneumonia in foals.

immunology↗