Passive Immunization with Hyperimmune Plasma to Protect Foals Against Rhodococcus equi Pneumonia

Abstract

Rhodococcus equi (R. equi) is a common cause of pneumonia in foals. The only product licensed by the United States Department of Agriculture (USDA) for reducing the incidence of R. equi pneumonia in foals is transfusion of hyperimmune plasma (HIP) derived from donors immunized against R. equi. The reported effectiveness of R. equi HIP (RE HIP) transfusion to prevent pneumonia in foals is variable. This variability is likely related to differences among studies in design and plasma products used. Thus, the first objective of this dissertation is to provide a literature review with a summary of the studies to better understand the clinical evidence of the efficacy of transfusing RE HIP to prevent pneumonia. The following chapters describe studies we conducted to investigate questions pertaining to the efficacy of HIP. First, we conducted a retrospective cohort study among foals transfused with either 2 L or ≤ 1 L of RE HIP to investigate the impact of the volume of plasma transfused for reducing the incidence of R. equi pneumonia. The proportion of the foals receiving ≤ 1 L RE HIP that developed subclinical pneumonia (32%; 26/82) was significantly (P= 0.0068) greater than that among foals transfused with 2 L of RE HIP (12%; 8/68). This led us to investigate whether pneumonia was associated with either serum antibody activities against the virulence-associated protein A (VapA) among foals transfused with 2 L of RE HIP, or with serum antibody activities against β-1→6-poly-N-acetyl glucosamine (PNAG, a polysaccharide expressed on the surface of R. equi and other bacteria) and deposition of complement component 1q (C՛1q) onto PNAG among foals transfused with PNAG HIP. This study demonstrated that the amount of antibody activity targeting R. equi antigens (VapA or PNAG) was positively associated with protection against R. equi pneumonia. Last, based on results of in vitro experiments, we tested the hypothesis that transfusion with PNAG HIP would be superior to RE HIP in foals for protecting against R. equi pneumonia in a randomized, controlled, blinded clinical trial. We found that there was no difference in protection between the plasma types.