FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / J Vet Intern Med / In vitro evaluation of complement deposition and opsonophago...
Journal of veterinary internal medicine2019; 33(3); 1493-1499; doi: 10.1111/jvim.15511

In vitro evaluation of complement deposition and opsonophagocytic killing of Rhodococcus equi mediated by poly-N-acetyl glucosamine hyperimmune plasma compared to commercial plasma products.

Abstract: The bacterium Rhodococcus equi can cause severe pneumonia in foals. The absence of a licensed vaccine and limited effectiveness of commercial R. equi hyperimmune plasma (RE-HIP) create a great need for improved prevention of this disease. Objective: Plasma hyperimmune to the capsular polysaccharide poly-N-acetyl glucosamine (PNAG) would be significantly more effective than RE-HIP at mediating complement deposition and opsonophagocytic killing (OPK) of R. equi. Methods: Venipuncture was performed on 9 Quarter Horses. Methods: The ability of the following plasma sources to mediate complement component 1 (C1) deposition onto either PNAG or R. equi was determined by ELISA: (1) PNAG hyperimmune plasma (PNAG-HIP), (2) RE-HIP, and (3) standard non-hyperimmune commercial plasma (SP). For OPK, each plasma type was combined with R. equi, equine complement, and neutrophils isolated from horses (n = 9); after 4 hours, the number of R. equi in each well was determined by quantitative culture. Data were analyzed using linear mixed-effects regression with significance set at P < .05. Results: The PNAG-HIP and RE-HIP were able to deposit significantly (P < .05) more complement onto their respective targets than the other plasmas. The mean proportional survival of R. equi opsonized with PNAG-HIP was significantly (P < .05) less (14.7%) than that for SP (51.1%) or RE-HIP (42.2%). Conclusions: Plasma hyperimmune to PNAG is superior to RE-HIP for opsonizing and killing R. equi in vitro. Comparison of these 2 plasmas in field trials is warranted because of the reported incomplete effectiveness of RE-HIP.
© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
Get Full Text
Publication Date: 2019-04-29 PubMed ID: 31034109PubMed Central: PMC6524092DOI: 10.1111/jvim.15511Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study investigated the effectiveness of a plasma hyperimmune to a specific capsular polysaccharide, poly-N-acetyl glucosamine (PNAG), in comparison to commercially available plasma products for fighting off infection caused by Rhodococcus equi bacteria. The researchers found that the plasma enhanced with poly-N-acetyl glucosamine was more effective at combating the bacteria in the laboratory setup than were the commercial products on the market.

Research Methodology

  • The experiment involved nine Quarter Horses from which venipunctures were performed for sample collection.
  • The researchers then analyzed the abilities of plasma products from varied sources to mediate deposition of complement component 1 (C1) onto either the bacterium Rhodococcus equi or the polysaccharide PNAG.
  • The assessment was carried out through an Enzyme-Linked Immunosorbent Assay (ELISA).
  • Evaluation was done on three types of plasmas: (1) PNAG hyperimmune plasma (PNAG-HIP), (2) Rhodococcus equi hyperimmune plasma (RE-HIP), and (3) standard non-hyperimmune commercial plasma (SP).
  • An opsonophagocytic killing (OPK) test was also performed. In this test, each of the above plasma types were combined with Rhodococcus equi bacteria, equine complement, and neutrophils isolated from the horses.
  • After a period of four hours, the number of Rhodococcus equi present in each setup was determined using quantitative culture.
  • Data analysis was performed using linear mixed-effects regression, and significance was set at P < .05.

Key Findings

  • The PNAG-HIP and RE-HIP were found to have a significantly greater ability (P < .05) than the other plasmas in depositing more complement onto their respective targets.
  • In terms of survival of the Rhodococcus equi bacteria, the results showed that the mean proportional survival rates for the bacteria opsonized with PNAG-HIP was significantly lower (14.7%) compared to that opsonized with SP (51.1%) or RE-HIP (42.2%).

Conclusions

The researchers concluded that the plasma hyperimmune to PNAG outperforms RE-HIP in opsonizing and killing Rhodococcus equi in vitro. As a result, they recommended a comparison of these two plasmas in field trials, given the reported incomplete effectiveness of RE-HIP. This research makes a significant contribution to the development of plasma products intended for addressing Rhodococcus equi infection.

Cite This Article

APA
Folmar CN, Cywes-Bentley C, Bordin AI, Rocha JN, Bray JM, Kahn SK, Schuckert AE, Pier GB, Cohen ND. (2019). In vitro evaluation of complement deposition and opsonophagocytic killing of Rhodococcus equi mediated by poly-N-acetyl glucosamine hyperimmune plasma compared to commercial plasma products. J Vet Intern Med, 33(3), 1493-1499. https://doi.org/10.1111/jvim.15511

Publication

Journal of veterinary internal medicine
ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 33
Issue: 3
Pages: 1493-1499

Researcher Affiliations

Folmar, Chelsea N
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas.
Cywes-Bentley, Colette
  • Department of Medicine, Harvard Medical School, Harvard University, Boston, Massachusetts.
Bordin, Angela I
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas.
Rocha, Joana N
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas.
Bray, Jocelyne M
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas.
Kahn, Susanne K
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas.
Schuckert, Amanda E
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas.
Pier, Gerald B
  • Department of Medicine, Harvard Medical School, Harvard University, Boston, Massachusetts.
Cohen, Noah D
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas.

MeSH Terms

  • Acetylglucosamine / immunology
  • Actinomycetales Infections / immunology
  • Actinomycetales Infections / veterinary
  • Animals
  • Antibodies, Bacterial / blood
  • Complement C1 / immunology
  • Female
  • Horse Diseases / immunology
  • Horse Diseases / microbiology
  • Horses / immunology
  • Male
  • Neutrophils
  • Plasma / immunology
  • Rhodococcus equi / immunology

Grant Funding

  • ALOPEXX Enterprises, Ltd. (Unrestricted Gift)
  • Chelsea Folmar was supported by the Boehringer-Ing / Boehringer-Ingelheim Animal Health
  • Link Equine Research Endowment, Texas A&M University
  • 5T32OD011083-08 / Office of Extramural Research, National Institutes of Health

Conflict of Interest Statement

Gerald B. Pier 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, and Alopexx Pharmaceuticals, LLC, entities in which Gerald B. Pier also holds equity. As an inventor of intellectual properties, Gerald B. Pier also has the right to receive a share of licensing‐related income (royalties, fees) through Brigham and Women's Hospital from Alopexx Pharmaceuticals, LLC, and Alopexx Vaccine, LLC. Gerald B. Pier's interests were reviewed and are managed by the Brigham and Women's Hospital and Partners Healthcare in accordance with their conflict of interest policies. Colette Cywes‐Bentley 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 Pharmaceuticals, LLC. As an inventor of intellectual properties, Colette Cywes‐Bentley also has the right to receive a share of licensing‐related income (royalties, fees) through Brigham and Women's Hospital from Alopexx Pharmaceuticals, LLC. Noah D. Cohen has received an unrestricted gift to the Equine Infectious Disease Laboratory at Texas A&M University to support research from Alopexx Vaccines, LLC.

References

This article includes 32 references
  1. Giguère S, Cohen ND, Chaffin MK, Slovis NM, Hondalus MK, Hines SA, Prescott JF. Diagnosis, treatment, control, and prevention of infections caused by Rhodococcus equi in foals.. J Vet Intern Med 2011 Nov-Dec;25(6):1209-20.
    pubmed: 22092608doi: 10.1111/j.1939-1676.2011.00835.xgoogle scholar: lookup
  2. Giguère S, Lee E, Williams E, Cohen ND, Chaffin MK, Halbert N, Martens RJ, Franklin RP, Clark CC, Slovis NM. Determination of the prevalence of antimicrobial resistance to macrolide antimicrobials or rifampin in Rhodococcus equi isolates and treatment outcome in foals infected with antimicrobial-resistant isolates of R equi.. J Am Vet Med Assoc 2010 Jul 1;237(1):74-81.
    pubmed: 20590498doi: 10.2460/javma.237.1.74google scholar: lookup
  3. Burton AJ, Giguère S, Sturgill TL, Berghaus LJ, Slovis NM, Whitman JL, Levering C, Kuskie KR, Cohen ND. Macrolide- and rifampin-resistant Rhodococcus equi on a horse breeding farm, Kentucky, USA.. Emerg Infect Dis 2013 Feb;19(2):282-5.
    pmc: PMC3559061pubmed: 23347878doi: 10.3201/eid1902.121210google scholar: lookup
  4. Rocha JN, Cohen ND, Bordin AI, Brake CN, Giguère S, Coleman MC, Alaniz RC, Lawhon SD, Mwangi W, Pillai SD. Oral Administration of Electron-Beam Inactivated Rhodococcus equi Failed to Protect Foals against Intrabronchial Infection with Live, Virulent R. equi.. PLoS One 2016;11(2):e0148111.
    pmc: PMC4735123pubmed: 26828865doi: 10.1371/journal.pone.0148111google scholar: lookup
  5. Sanz MG, Oliveira AF, Page A, Horohov DW. Administration of commercial Rhodococcus equi specific hyperimmune plasma results in variable amounts of IgG against pathogenic bacteria in foals.. Vet Rec 2014 Nov 15;175(19):485.
    pubmed: 25117301doi: 10.1136/vr.102594google scholar: lookup
  6. Caston SS, McClure SR, Martens RJ, Chaffin MK, Miles KG, Griffith RW, Cohen ND. Effect of hyperimmune plasma on the severity of pneumonia caused by Rhodococcus equi in experimentally infected foals.. Vet Ther 2006 Winter;7(4):361-75.
    pubmed: 17216591
  7. Higuchi T, Arakawa T, Hashikura S, Inui T, Senba H, Takai S. Effect of prophylactic administration of hyperimmune plasma to prevent Rhodococcus equi infection on foals from endemically affected farms.. Zentralbl Veterinarmed B 1999 Nov;46(9):641-8.
    pubmed: 10605374doi: 10.1046/j.1439-0450.1999.00284.xgoogle scholar: lookup
  8. Giguère S, Gaskin JM, Miller C, Bowman JL. Evaluation of a commercially available hyperimmune plasma product for prevention of naturally acquired pneumonia caused by Rhodococcus equi in foals.. J Am Vet Med Assoc 2002 Jan 1;220(1):59-63.
    pubmed: 12680449doi: 10.2460/javma.2002.220.59google scholar: lookup
  9. Hurley JR, Begg AP. Failure of hyperimmune plasma to prevent pneumonia caused by Rhodococcus equi in foals.. Aust Vet J 1995 Nov;72(11):418-20.
    pubmed: 8929188doi: 10.1111/j.1751-0813.1995.tb06192.xgoogle scholar: lookup
  10. Madigan JE, Hietala S, Muller N. Protection against naturally acquired Rhodococcus equi pneumonia in foals by administration of hyperimmune plasma.. J Reprod Fertil Suppl 1991;44:571-8.
    pubmed: 1795301
  11. Martens RJ, Martens JG, Fiske RA, Hietala SK. Rhodococcus equi foal pneumonia: protective effects of immune plasma in experimentally infected foals.. Equine Vet J 1989 Jul;21(4):249-55.
    pubmed: 2767025doi: 10.1111/j.2042-3306.1989.tb02161.xgoogle scholar: lookup
  12. Sanz MG, Loynachan A, Horohov DW. Rhodococcus equi hyperimmune plasma decreases pneumonia severity after a randomised experimental challenge of neonatal foals.. Vet Rec 2016 Mar 12;178(11):261.
    pubmed: 26932206doi: 10.1136/vr.103095google scholar: lookup
  13. Becú T, Polledo G, Gaskin JM. Immunoprophylaxis of Rhodococcus equi pneumonia in foals.. Vet Microbiol 1997 Jun 16;56(3-4):193-204.
    pubmed: 9226834doi: 10.1016/s0378-1135(97)00088-6google scholar: lookup
  14. Cywes-Bentley C, Skurnik D, Zaidi T, Roux D, Deoliveira RB, Garrett WS, Lu X, O'Malley J, Kinzel K, Zaidi T, Rey A, Perrin C, Fichorova RN, Kayatani AK, Maira-Litràn T, Gening ML, Tsvetkov YE, Nifantiev NE, Bakaletz LO, Pelton SI, Golenbock DT, Pier GB. Antibody to a conserved antigenic target is protective against diverse prokaryotic and eukaryotic pathogens.. Proc Natl Acad Sci U S A 2013 Jun 11;110(24):E2209-18.
    pmc: PMC3683766pubmed: 23716675doi: 10.1073/pnas.1303573110google scholar: lookup
  15. Cywes-Bentley C, Rocha JN, Bordin AI, Vinacur M, Rehman S, Zaidi TS, Meyer M, Anthony S, Lambert M, Vlock DR, Giguère S, Cohen ND, Pier GB. Antibody to Poly-N-acetyl glucosamine provides protection against intracellular pathogens: Mechanism of action and validation in horse foals challenged with Rhodococcus equi.. PLoS Pathog 2018 Jul;14(7):e1007160.
    pmc: PMC6053243pubmed: 30024986doi: 10.1371/journal.ppat.1007160google scholar: lookup
  16. Maira-Litrán T, Kropec A, Goldmann DA, Pier GB. Comparative opsonic and protective activities of Staphylococcus aureus conjugate vaccines containing native or deacetylated Staphylococcal Poly-N-acetyl-beta-(1-6)-glucosamine.. Infect Immun 2005 Oct;73(10):6752-62.
    pmc: PMC1230901pubmed: 16177353doi: 10.1128/iai.73.10.6752-6762.2005google scholar: lookup
  17. Sidak Z. Rectangular confidence regions for the means of multivariate normal distributions.. J Am Stat Assoc 1967;62:626‐633.
  18. Brown EJ, Joiner KA, Frank MM. The role of complement in host resistance to bacteria.. Springer Semin Immunopathol 1983;6(4):349-60.
    pubmed: 6364430doi: 10.1007/bf02116279google scholar: lookup
  19. Cunnion KM, Zhang HM, Frank MM. Availability of complement bound to Staphylococcus aureus to interact with membrane complement receptors influences efficiency of phagocytosis.. Infect Immun 2003 Feb;71(2):656-62.
    pmc: PMC145377pubmed: 12540542doi: 10.1128/iai.71.2.656-662.2003google scholar: lookup
  20. Giguère S, Polkes AC. Immunologic disorders in neonatal foals.. Vet Clin North Am Equine Pract 2005 Aug;21(2):241-72, v.
    pubmed: 16051049doi: 10.1016/j.cveq.2005.04.004google scholar: lookup
  21. Freccero F, Mariella J, Lanci A, Cotignoli C, Castagnetti C. Efficacy and safety of a commercial fresh‐frozen hyperimmune plasma in foals with failure of passive transfer of immunity.. J Equine Vet Sci 2017;48:147‐181.
  22. Perkins GA, Yeager A, Erb HN, Nydam DV, Divers TJ, Bowman JL. Survival of foals with experimentally induced Rhodococcus equi infection given either hyperimmune plasma containing R. equi antibody or normal equine plasma.. Vet Ther 2002 Fall;3(3):334-46.
    pubmed: 12447842
  23. Gröndahl G, Johannisson A, Demmers S, Jensen Waern M. Influence of age and plasma treatment on neutrophil phagocytosis and CD18 expression in foals.. Vet Microbiol 1999 Mar 12;65(3):241-54.
    pubmed: 10189199doi: 10.1016/s0378-1135(98)00299-5google scholar: lookup
  24. Gröndahl G, Sternberg S, Jensen-Waern M, Johannisson A. Opsonic capacity of foal serum for the two neonatal pathogens Escherichia coli and Actinobacillus equuli.. Equine Vet J 2001 Nov;33(7):670-5.
    pubmed: 11770988doi: 10.2746/042516401776249381google scholar: lookup
  25. Demmers S, Johannisson A, Gröndahl G, Jensen-Waern M. Neutrophil functions and serum IgG in growing foals.. Equine Vet J 2001 Nov;33(7):676-80.
    pubmed: 11770989doi: 10.2746/042516401776249327google scholar: lookup
  26. McTaggart C, Penhale J, Raidala SL. Effect of plasma transfusion on neutrophil function in healthy and septic foals.. Aust Vet J 2005 Aug;83(8):499-505.
    pubmed: 16119424doi: 10.1111/j.1751-0813.2005.tb13304.xgoogle scholar: lookup
  27. Nerren JR, Martens RJ, Payne S, Murrell J, Butler JL, Cohen ND. Age-related changes in cytokine expression by neutrophils of foals stimulated with virulent Rhodococcus equi in vitro.. Vet Immunol Immunopathol 2009 Feb 15;127(3-4):212-9.
    pubmed: 19026456doi: 10.1016/j.vetimm.2008.10.004google scholar: lookup
  28. Liu M, Liu T, Bordin A, Nerren J, Cohen N. Activation of foal neutrophils at different ages by CpG oligodeoxynucleotides and Rhodococcus equi.. Cytokine 2009 Dec;48(3):280-9.
    pubmed: 19819162doi: 10.1016/j.cyto.2009.08.012google scholar: lookup
  29. Bordin AI, Liu M, Nerren JR, Buntain SL, Brake CN, Kogut MH, Cohen ND. Neutrophil function of neonatal foals is enhanced in vitro by CpG oligodeoxynucleotide stimulation.. Vet Immunol Immunopathol 2012 Jan 15;145(1-2):290-7.
    pubmed: 22197007doi: 10.1016/j.vetimm.2011.11.012google scholar: lookup
  30. Cohen ND, Bourquin JR, Bordin AI, Kuskie KR, Brake CN, Weaver KB, Liu M, Felippe MJ, Kogut MH. Intramuscular administration of a synthetic CpG-oligodeoxynucleotide modulates functional responses of neutrophils of neonatal foals.. PLoS One 2014;9(10):e109865.
    pmc: PMC4198146pubmed: 25333660doi: 10.1371/journal.pone.0109865google scholar: lookup
  31. Dindot SV, Doan RN, Kuskie KR, Hillman PR, Whitfield CM, McQueen CM, Bordin AI, Bourquin JR, Cohen ND. Postnatal changes in epigenetic modifications of neutrophils of foals are associated with increased ROS function and regulation of neutrophil function.. Dev Comp Immunol 2018 Oct;87:182-187.
    pubmed: 29958850doi: 10.1016/j.dci.2018.06.012google scholar: lookup
  32. Cohen ND, Smith KE, Ficht TA, Takai S, Libal MC, West BR, DelRosario LS, Becu T, Leadon DP, Buckley T, Chaffin MK, Martens RJ. Epidemiologic study of results of pulsed-field gel electrophoresis of isolates of Rhodococcus equi obtained from horses and horse farms.. Am J Vet Res 2003 Feb;64(2):153-61.
    pubmed: 12602583doi: 10.2460/ajvr.2003.64.153google scholar: lookup

Citations

This article has been cited 6 times.
  1. Rivolta AA, Bujold AR, Wilmarth PA, Phinney BS, Navelski JP, Horohov DW, Sanz MG. Comparison of the broncoalveolar lavage fluid proteomics between foals and adult horses.. PLoS One 2023;18(9):e0290778.
    doi: 10.1371/journal.pone.0290778pubmed: 37669266google scholar: lookup
  2. Kahn SK, Cywes-Bentley C, Blodgett GP, Canaday NM, Turner-Garcia CE, Flores-Ahlschwede P, Metcalfe LL, Nevill M, Vinacur M, Sutter PJ, Meyer SC, Bordin AI, Pier GB, Cohen ND. Randomized, controlled trial comparing Rhodococcus equi and poly-N-acetyl glucosamine hyperimmune plasma to prevent R equi pneumonia in foals.. J Vet Intern Med 2021 Nov;35(6):2912-2919.
    doi: 10.1111/jvim.16294pubmed: 34738651google scholar: lookup
  3. 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. 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 2021;16(8):e0250133.
    doi: 10.1371/journal.pone.0250133pubmed: 34437551google scholar: lookup
  4. Cohen ND, Kahn SK, Cywes-Bentley C, Ramirez-Cortez S, Schuckert AE, Vinacur M, Bordin AI, Pier GB. Serum Antibody Activity against Poly-N-Acetyl Glucosamine (PNAG), but Not PNAG Vaccination Status, Is Associated with Protecting Newborn Foals against Intrabronchial Infection with Rhodococcus equi.. Microbiol Spectr 2021 Sep 3;9(1):e0063821.
    doi: 10.1128/Spectrum.00638-21pubmed: 34319137google scholar: lookup
  5. Bordin AI, Cohen ND, Giguère S, Bray JM, Berghaus LJ, Scott B, Johnson R, Hook M. Host-directed therapy in foals can enhance functional innate immunity and reduce severity of Rhodococcus equi pneumonia.. Sci Rep 2021 Jan 28;11(1):2483.
    doi: 10.1038/s41598-021-82049-ypubmed: 33510265google scholar: lookup
  6. Harvey AB, Bordin AI, Rocha JN, Bray JM, Cohen ND. Opsonization but not pretreatment of equine macrophages with hyperimmune plasma nonspecifically enhances phagocytosis and intracellular killing of Rhodococcus equi.. J Vet Intern Med 2021 Jan;35(1):590-596.
    doi: 10.1111/jvim.16002pubmed: 33326149google scholar: lookup
Subscribe to our newsletter
Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.