Antibody Activities in Hyperimmune Plasma Against theRhodococcus equiVirulence-Associated Protein A or Poly-N-Acetyl Glucosamine are Associated with Protection of Foals Against Rhodococcal Pneumonia

Abstract

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 β-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 (C?1q) 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 C?1q 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 C?1q deposition (an indicator of functional antibodies) were a stronger predictor of protection than 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.

Rhodococcus equifoal pneumonia: Update on epidemiology, immunity, treatment and prevention

“…Although transfusion of 2 L appears safe, [171][172][173][174] efforts to develop alternative approaches to passive immunisation (e.g. concentrated antibody products) are needed to improve convenience and safety of passive immunisation of foals to control R. equi pneumonia.…”

“…Results of 2 retrospective cohort studies indicate that foals transfused with 2 L of R. equi hyperimmune plasma were significantly less likely to develop either subclinical 172 or clinical 173 R. equi pneumonia than foals transfused with 1 L of plasma. Because of the limitations of observational studies, well‐designed clinical trials are needed to determine the relative efficacy of transfusing 2 L vs. 1 L. Recently, higher serum antibody activities in hyperimmune plasma against either VapA or PNAG were demonstrated to be associated with protection against rhodococcal pneumonia in foals at two large breeding farms in the US 174 . Collectively, these findings indicate that a larger volume or higher concentration of antigen‐specific antibodies in plasma is likely to reduce the risk of rhodococcal pneumonia in foals.…”

“…Collectively, these findings indicate that a larger volume or higher concentration of antigen‐specific antibodies in plasma is likely to reduce the risk of rhodococcal pneumonia in foals. Although transfusion of 2 L appears safe, 171–174 efforts to develop alternative approaches to passive immunisation (e.g. concentrated antibody products) are needed to improve convenience and safety of passive immunisation of foals to control R. equi pneumonia.…”