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

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 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.

Transfusion of hyperimmune plasma for protecting foals againstRhodococcus equipneumonia

“…Results showed that the odds of pneumonia were significantly higher for foals transfused with RE hyperimmune plasma that had lower antibody activity against VapA and and for foals transfused with PNAG hyperimmune plasma that had either lower activity of PNAG or less deposition of complement component 1q (C 0 1q) onto PNAG. 55 The role of the relative or absolute amount of IgG sub-isotype(s) recognising R. equi antigens in the efficacy of RE hyperimmune plasma is unknown. Conflicting evidence exists regarding the association of IgG sub-isotypes with R. equi infection.…”

“…Although several studies 8,40,41,48,55,66,67,75 indicate that transfusion of hyperimmune plasma to foals at age ≤ 24 h is safe, inherent risks associated with plasma transfusion including hypersensitivity reactions, [93][94][95][96] transfusion-related lung injury (TRALI), [97][98][99][100] transfusionassociated circulatory overload (TACO), 100 virus transmission, 101,102 intravenous catheterisation of foals, and handling foals. In a retrospective study reporting the incidence of transfusion reactions between 2003 and 2005 of 107 client-owned horses referred to the University of Wisconsin teaching hospital transfused with plasma, 6% (6/107) of horses had an adverse reaction and all were in foals <7 days of age.…”

“…100 To the authors' knowledge, neither TRALI nor TACO have been reported in foals transfused with RE hyperimmune plasma, and adverse reactions have not been reported among foals transfused with RE hyperimmune plasma soon after birth. 8,40,41,48,55,66,67,75 Transmission of viruses such as equine parvovirus hepatitis (the presumed cause of Theiler's disease), 101,102 is another risk associated with transfusion. To help mitigate this risk, manufacturers of plasma and serum products in the United States are required by the USDA to follow testing protocols for their donor herd for equine infectious anaemia (EIA), piroplasmosis, dourine, glanders and brucellosis.…”

“…in expanding blood volume by approximately 40%. Although this procedure has been performed in hundreds of foals without reports of adverse effects, 8,55,66,67,75 TACO is recognised in human beings after transfusions. 100 Thus, alternative approaches for delivering antibodies are warranted.…”

“…In a recent study from our laboratory, foals were transfused with 2 L of either RE hyperimmune plasma or plasma hyperimmunised against β‐1 → 6 poly‐ N ‐acetyl glucosamine (PNAG hyperimmune plasma) within 24 h of birth. Results showed that the odds of pneumonia were significantly higher for foals transfused with RE hyperimmune plasma that had lower antibody activity against VapA and and for foals transfused with PNAG hyperimmune plasma that had either lower activity of PNAG or less deposition of complement component 1q (C′1q) onto PNAG 55 …”