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.

Sarah C. Meyer,Mariana Vinacur,Angela I. Bordin,Colette Cywes-Bentley,Glenn P. Blodgett,Daniel R. Vlock,Patrick J. Sutter,Carly E. Turner-Garcia,Sophia C. Cortez-Ramirez,Ashlesh K. Murthy,Nathan M. Canaday,Noah D. Cohen,Gerald B. Pier,Susanne K. Kahn

doi:10.1371/journal.pone.0250133

Sarah C. Meyer, Mariana Vinacur + Show 12 more

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https://doi.org/10.1371/journal.pone.0250133

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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.

Highlights

Rhodococcus equi (R. equi) is a common cause of severe pneumonia in foals [1–5]
Farm B had a total of 114 foals included; 57 foals were transfused with RE hyperimmune plasma (HIP), and 57 foals were transfused with poly-N-acetyl glucosamine (PNAG) HIP
Optical densities (ODs) ratios of virulence-associated protein A (VapA) antibodies were significantly (P < 0.05) higher among foals transfused with R. equi hyperimmune plasma (RE HIP) than with PNAG HIP (Fig 1)

Summary

Introduction

Rhodococcus equi (R. equi) is a common cause of severe pneumonia in foals [1–5]. Virulent strains of this facultative, intracellular pathogen contain a plasmid that encodes for the virulence-associated protein A (VapA) that is necessary for bacterial replication in macrophages [6]. Costs can be high for treatment, veterinary care, long-term therapy, and lost revenue from deaths of foals infected with R. equi In addition to these immediate costs, R. equi pneumonia has a long-term detrimental effect to the equine industry because foals that recover from the disease are less likely to race as adults [10]. Foals with ultrasonographically-identified pulmonary lesions greater than a certain threshold of a maximal diameter (e.g., 2 cm of maximum diameter) but lacking other clinical signs are often treated with antimicrobials [12]. The rationale for this screen-and-treat approach is that it will reduce mortality and duration of treatment of foals at endemic farms [12]

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