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.
Publication Date: 2021-08-26 PubMed ID: 34437551PubMed Central: PMC8389416DOI: 10.1371/journal.pone.0250133Google Scholar: Lookup
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Summary
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Research on Rhodococcus equi, a bacterium causing pneumonia in young horses, was conducted. They studied the effects of plasma transfusion from hyperimmune adult horses, focusing on the impact of two types of hyperimmune plasma on foals’ resistance to pneumonia.
Methodology
- The study was conducted on Quarter Horse foals at two large breeding farms. Foals were randomly assigned to receive transfusion of either Rhodococcus equi hyperimmune plasma (RE HIP) or plasma rich in antibodies against the β-1→6-poly-N-acetyl glucosamine (PNAG) polysaccharide within 24 hours of birth.
- The antibody activity against PNAG, Rhodococcus equi virulence-associated protein A (VapA), and the deposition of complement component 1q (C՛1q) on PNAG were measured via an ELISA (Enzyme-Linked Immunosorbent Assay), a type of laboratory test that measures the amount of a specific substance (in this case, antibodies) in a sample.
- The results were then compared with the incidence of clinical pneumonia at one farm and subclinical pneumonia (pneumonia showing no symptoms) at the other. Statistical analysis was carried out using multivariable logistic regression.
Findings
- Among foals receiving RE HIP, those with VapA antibody activity at or below the median population level had approximately six times higher odds of developing pneumonia.
- Among foals receiving PNAG HIP, those with PNAG or C՛1q antibody activity at or below the median had approximately 3 and 11 times higher odds of pneumonia, respectively.
- Therefore, higher levels of antibodies against Rhodococcus equi were associated with better protection against pneumonia.
Implications
- The study suggests that the volume and/or activity of antibodies in hyperimmune plasma is positively related to protection against Rhodococcus equi pneumonia in foals.
- The activity of antibodies with C՛1q deposition (which indicates functioning antibodies) was a stronger predictor of protection than the antibody activity against PNAG alone.
- This has potential implications for the development of more effective interventions to protect foals against Rhodococcus equi pneumonia, possibly through the use of plasma transfusions from hyperimmunized adult horses.
Cite This Article
APA
Kahn SK, Cywes-Bentley C, Blodgett GP, Canaday NM, Turner-Garcia CE, Vinacur M, Cortez-Ramirez SC, Sutter PJ, Meyer SC, Bordin AI, Vlock DR, Pier GB, Cohen ND.
(2021).
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.
PLoS One, 16(8), e0250133.
https://doi.org/10.1371/journal.pone.0250133 Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, Equine Infectious Disease Laboratory, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, United States of America.
- Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, United States of America.
- 6666 Ranch, Guthrie, TX, United States of America.
- 6666 Ranch, Guthrie, TX, United States of America.
- Lazy E Ranch, Guthrie, OK, United States of America.
- Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, United States of America.
- Department of Large Animal Clinical Sciences, Equine Infectious Disease Laboratory, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, United States of America.
- Mg Biologics, Inc., Ames, IA, United States of America.
- Mg Biologics, Inc., Ames, IA, United States of America.
- Department of Large Animal Clinical Sciences, Equine Infectious Disease Laboratory, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, United States of America.
- Alopexx Inc., Concord, MA, United States of America.
- Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, United States of America.
- Department of Large Animal Clinical Sciences, Equine Infectious Disease Laboratory, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, United States of America.
MeSH Terms
- Acetylglucosamine / immunology
- Actinomycetales Infections / immunology
- Actinomycetales Infections / microbiology
- Actinomycetales Infections / prevention & control
- Actinomycetales Infections / veterinary
- Animals
- Animals, Newborn / immunology
- Animals, Newborn / microbiology
- Antibodies, Bacterial / immunology
- Antibodies, Bacterial / therapeutic use
- Bacterial Proteins / immunology
- Female
- Horse Diseases / immunology
- Horse Diseases / microbiology
- Horse Diseases / prevention & control
- Horses / immunology
- Horses / microbiology
- Immunization, Passive / methods
- Immunization, Passive / veterinary
- Male
- Pneumonia, Bacterial / immunology
- Pneumonia, Bacterial / microbiology
- Pneumonia, Bacterial / prevention & control
- Pneumonia, Bacterial / veterinary
- Rhodococcus equi / immunology
Conflict of Interest Statement
I have read the journal’s policy and the authors of this manuscript have the following competing interests: Gerald B. Pier (GBP) is an inventor of intellectual properties [human monoclonal antibody to PNAG and PNAG vaccines] that are licensed by Brigham and Women’s Hospital to Alopexx Vaccine, LLC, an entity in which GBP also holds equity. As an inventor of intellectual properties, GBP also has the right to receive a share of licensing-related income (royalties, fees) through Brigham and Women’s Hospital from Alopexx Vaccine, LLC. GBP’s interests were reviewed and are managed by the Brigham and Women’s Hospital and Partners Health care in accordance with their conflict of interest policies. Colette Cywes-Bentley (CC-B) is an inventor of intellectual properties [use of human monoclonal antibody to PNAG and use of PNAG vaccines] that are licensed by Brigham and Women’s Hospital to Alopexx Vaccine, LLC. As an inventor of intellectual properties, CC-B also has the right to receive a share of licensing-related income (royalties, fees) through Brigham and Women’s Hospital from Alopexx Vaccine, LLC. Daniel R. Vlock is the Chief Executive Officer of ALOPEXX Vaccines and owns the rights to the PNAG vaccine. Dr. Vlock had no role in the design or analysis of the study. SC Meyer and PJ Sutter work for MG Biologics that produced the plasma and thus might have potential earnings; however, they had no part in the design or analysis of the study. Drs. Glenn Blodgett and Nathan Canaday are employees of the 6666 Ranch and Dr. Carly Turner-Garcia is employed by the Lazy E Ranch. Sarah Meyer and Patrick Sutter are employed by Mg Biologics, Inc. and Dr. Daniel Vlock is employed by ALOPEXX Vaccines. The 6666 Ranch, Lazy E Ranch, Mg Biologics, and ALOPEXX provided support in the form of salaries, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
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Citations
This article has been cited 1 times.- da Silveira BP, Kahn SK, Legere RM, Bray JM, Cole-Pfeiffer HM, Golding MC, Cohen ND, Bordin AI. Enteral immunization with live bacteria reprograms innate immune cells and protects neonatal foals from pneumonia. Sci Rep 2025 May 25;15(1):18156.
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