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PloS one2020; 15(10); e0240479; doi: 10.1371/journal.pone.0240479

Vaccination of yearling horses against poly-N-acetyl glucosamine fails to protect against infection with Streptococcus equi subspecies equi.

Abstract: Strangles is a common disease of horses with worldwide distribution caused by the bacterium Streptococcus equi subspecies equi (SEE). Although vaccines against strangles are available commercially, these products have limitations in safety and efficacy. The microbial surface antigen β 1→6 poly-N-acetylglucosamine (PNAG) is expressed by SEE. Here we show that intramuscular (IM) injection alone or a combination of IM plus intranasal (IN) immunization generated antibodies to PNAG that functioned to deposit complement and mediate opsonophagocytic killing of SEE ex vivo. However, immunization strategies targeting PNAG either by either IM only injection or a combination of IM and IN immunizations failed to protect yearling horses against infection following contact with infected horses in an experimental setting. We speculate that a protective vaccine against strangles will require additional components, such as those targeting SEE enzymes that degrade or inactivate equine IgG.
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Publication Date: 2020-10-15 PubMed ID: 33057397PubMed Central: PMC7561144DOI: 10.1371/journal.pone.0240479Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

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.

The research paper discusses an unsuccessful attempt to protect yearling horses from a bacterium reported to cause strangles, a common horse disease, through vaccination targeting a specific antigen expressed by the bacterium.

Introduction and Background

  • The paper centers on a condition known as strangles, which is a prevalent and widely distributed disease affecting horses globally. This disease is caused by Streptococcus equi subspecies equi (SEE), a particular bacterium.
  • Despite the existence of vaccines created to combat strangles, the effectiveness and safety of these vaccines have posed significant concerns. The research aims to address these limitations through the potential use of another type of vaccine targeting the microbial surface antigen β 1→6 poly-N-acetylglucosamine (PNAG), which is produced by SEE.

Methodology and Experimental Outcome

  • The researchers administered intramuscular (IM) injections alone or combined IM and intranasal (IN) immunizations to generate antibodies to PNAG in horses. These antibodies functioned to deposit complement (a component of the immune system) while also facilitating the process of opsonophagocytic killing of SEE ex vivo (outside a living organism).
  • Unfortunately, the immunization strategies targeting PNAG failed to protect yearling horses from infection when contact was made with infected horses, demonstrating that this approach does not work under experimental conditions.

Implications and Speculations

  • The study’s findings imply that the immunity generation mechanism via PNAG targeted immunization is ineffective against the strangles causing bacterium in a real-world setting, despite being theoretically valid.
  • The researchers speculate that a protective vaccine against strangles will need supplementary elements. For instance, components targeting SEE enzymes that degrade or neutralize horse IgG (a type of antibody) might be required to create a potent and protective response against the disease-causing bacteria.

Cite This Article

APA
Cohen ND, Cywes-Bentley C, Kahn SM, Bordin AI, Bray JM, Wehmeyer SG, Pier GB. (2020). Vaccination of yearling horses against poly-N-acetyl glucosamine fails to protect against infection with Streptococcus equi subspecies equi. PLoS One, 15(10), e0240479. https://doi.org/10.1371/journal.pone.0240479

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 15
Issue: 10
Pages: e0240479

Researcher Affiliations

Cohen, Noah D
  • Equine Infectious Disease Laboratory, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, United States of America.
Cywes-Bentley, Colette
  • Harvard Medical School, Brigham & Women's Hospital, Boston, MA, United States of America.
Kahn, Susanne M
  • Equine Infectious Disease Laboratory, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, United States of America.
Bordin, Angela I
  • Equine Infectious Disease Laboratory, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, United States of America.
Bray, Jocelyne M
  • Equine Infectious Disease Laboratory, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, United States of America.
Wehmeyer, S Garrett
  • Equine Infectious Disease Laboratory, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, United States of America.
Pier, Gerald B
  • Harvard Medical School, Brigham & Women's Hospital, Boston, MA, United States of America.

MeSH Terms

  • Acetylglucosamine / immunology
  • Animals
  • Antibodies, Bacterial / immunology
  • Female
  • Horse Diseases / immunology
  • Horse Diseases / microbiology
  • Horses
  • Immunization
  • Injections, Intramuscular
  • Male
  • Streptococcal Infections / immunology
  • Streptococcal Infections / microbiology
  • Streptococcal Infections / veterinary
  • Streptococcus equi / immunology
  • Vaccination / veterinary

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 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 Pharmaceuticals, LLC, and Alopexx Vaccine, LLC. GBP’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, CC-B also has the right to receive a share of licensing-related income (royalties, fees) through Brigham and Women’s Hospital from Alopexx Pharmaceuticals, LLC. The remaining authors have declared no competing interests exist. This does not alter our adherence to  PLOS ONE policies on sharing data and materials.

References

This article includes 26 references
  1. Paillot R, Lopez-Alvarez R, Newton JR, Waller AS. Strangles: A modern clinical view from the 17th century.. Equine Vet J 2017;49:141–145.
    doi: 10.1111/evj.12659pubmed: 28177153google scholar: lookup
  2. Waller AS, Paillot R, Timoney JF. Streptococcus equi: a pathogen restricted to one host.. J Med Microbiol 2011;60(Pt 9):1231–1240.
    doi: 10.1099/jmm.0.028233-0pubmed: 21757503google scholar: lookup
  3. Sweeney CR, Timoney JF, Newton JR, Hines MT. Streptococcus equi infections in the horses: guidelines for treatment, control, and prevention of strangles.. J Vet Intern Med 2005;19:123–134.
    pubmed: 15715061
  4. Slater JD. Strangles, bastard strangles, vives, and glanders: archeological relics in a genomic age.. Equine Vet J 2003;35:118–120.
    doi: 10.2746/042516403776114252pubmed: 12638785google scholar: lookup
  5. Boyle AG, Timoney JF, Newton JR, Hines MT, Waller AS, Buchanan BR. Streptococcus equi Infections in horses: Guidelines for treatment, control, and prevention of strangles-revised consensus statement.. J Vet Intern Med 2018;32(2):633–647.
    doi: 10.1111/jvim.15043pmc: PMC5867011pubmed: 29424487google scholar: lookup
  6. Borst LB, Patterson SK, Lanka S, Barger AM, Fredrickson RL, Maddox CW. Evaluation of a commercially available modified-live Streptococcus equi subsp equi vaccine in ponies.. Am J Vet Res 2011;72(8):1130–1138.
    doi: 10.2460/ajvr.72.8.1130pubmed: 21801073google scholar: lookup
  7. Cursons R, Patty O, Steward KF, Waller AS. Strangles in horses can be caused by vaccination with Pinnacle I.N.. Vaccine 2015;33:3340–3443.
    pubmed: 26025806
  8. Morris ERA, Hillhouse AE, Konganti K, Wu J, Lawhon SD, Bordin AI. Comparison of whole genome sequences of Streptococcus equi subsp. equi from an outbreak in Texas with isolates from within the region, Kentucky, USA, and other countries.. Vet Microbiol 2020;243:108638.
    doi: 10.1016/j.vetmic.2020.108638pubmed: 32273017google scholar: lookup
  9. Sweeney CR, Whitlock RH, Meirs DA, Whitehead SC, Barningham SO. Complications associated with Streptococcus equi infection on a horse farm.. J Am Vet Med Assoc 1987;191:1446–1448.
    pubmed: 3692991
  10. Pusterla N, Watson JL, Affolter VK, Magdesian KG, Carlson GP. Purpura haemorrhagica in 53 horses.. Vet Rec 2003;153: 118–121.
    doi: 10.1136/vr.153.4.118pubmed: 12918829google scholar: lookup
  11. Delph KM, Beard LA, Trimble AC, Sutter ME, Timoney JF, Morrow JK. Strangles, convalescent Streptococcus equi subspecies equi M antibody titers, and presence of complications.. J Vet Intern Med 2019;33(1):275–279.
    doi: 10.1111/jvim.15388pmc: PMC6335513pubmed: 30520521google scholar: lookup
  12. Sponseller BT, Valberg SJ, Tennent-Brown BS, Foreman JH, Kumar P, Timoney JF. Severe acute rhabdomyolysis associated with Streptococcus equi infection in four horses.. J Am Vet Med Assoc 2005;227:1800–1807.
    doi: 10.2460/javma.2005.227.1800pubmed: 16342530google scholar: lookup
  13. Kaese HJ, Valberg SJ, Hayden DW, Wilson JH, Charlton P, Ames TR. Infarctive purpura hemorrhagica in five horses.. J Am Vet Med Assoc 2005;226:1893–1898.
    doi: 10.2460/javma.2005.226.1893pubmed: 15934258google scholar: lookup
  14. Cywes-Bentley C, Rocha JN, Bordin AI, Vinacur M, Rehman S, Zaidi TS. Antibody to poly-N-acetyl glucosamine provides protection against intracellular pathogens: Mechanism of action and validation in horse foals challenged with Rhodococcus equi.. PLoS One 2018;14(7):e1007160.
    pmc: PMC6053243pubmed: 30024986
  15. D’Gama JD, Ma Z, Zhang H, Liu X, Fan H, Morris ERA. A conserved streptococcal virulence regulator controls the expression of a distinct class of M-like proteins.. mBio 2019;10(5):e02500–19.
    doi: 10.1128/mBio.02500-19pmc: PMC6805998pubmed: 31641092google scholar: lookup
  16. Cywes-Bentley C, Skurnik D, Zaidi T, Roux D, Deoliveira RB, Garrett WS. Antibody to a conserved antigenic target is protective against diverse prokaryotic and eukaryotic pathogens.. Proc Natl Acad Sci U S A 2013;110:E2209–18.
    doi: 10.1073/pnas.1303573110pmc: PMC3683766pubmed: 23716675google scholar: lookup
  17. Kelly-Quintos C, Cavacini LA, Posner MR, Goldmann D, Pier GB. Characterization of the opsonic and protective activity against Staphylococcus aureus of fully human monoclonal antibodies specific for the bacterial surface polysaccharide poly-N-acetylglucosamine.. Infect Immun 2006;74:2742–2750.
    doi: 10.1128/IAI.74.5.2742-2750.2006pmc: PMC1459728pubmed: 16622211google scholar: lookup
  18. Kelly-Quintos C, Kropec A, Briggs S, Ordonez C, Goldmann DA, Pier GB. The role of epitope specificity in the human opsonic antibody response to the staphylococcal surface polysaccharide PNAG.. J Infect Dis 2005;192:2012–2019.
    doi: 10.1086/497604pubmed: 16267775google scholar: lookup
  19. Skurnik D, Merighi M, Grout M, Gadjeva M, Maira-Litran T, Ericsson M. Animal and human antibodies to distinct Staphylococcus aureus antigens mutually neutralize opsonic killing and protection in mice.. J Clin Invest 2010;9:3220–3233.
    pmc: PMC2929724pubmed: 20739753
  20. Maira-Litran 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.. Infection and immunity 2005;73:6752–62.
    doi: 10.1128/IAI.73.10.6752-6762.2005pmc: PMC1230901pubmed: 16177353google scholar: lookup
  21. Gening ML, Maira-Litran T, Kropec A, Skurnik D, Grout M, Tsvetkov YE. Synthetic β-(1->6)-linked N-acetylated and nonacetylated oligoglucosamines used to produce conjugate vaccines for bacterial pathogens.. Infect Immun 2010;78:764–72.
    doi: 10.1128/IAI.01093-09pmc: PMC2812210pubmed: 19948836google scholar: lookup
  22. Pozzi C, Wilk K, Lee JC, Gening M, Nifantiev N, Pier GB. Opsonic and protective properties of antibodies raised to conjugate vaccines targeting six Staphylococcus aureus antigens.. PloS One 2012;7:e46648.
    doi: 10.1371/journal.pone.0046648pmc: PMC3471903pubmed: 23077517google scholar: lookup
  23. Lannergård J, Guss B. IdeE, an IgG-endopeptidase of Streptococcus equi ssp. equi.. FEMS Microbiol Lett 2006;262:230–235.
    doi: 10.1111/j.1574-6968.2006.00404.xpubmed: 16923080google scholar: lookup
  24. Hulting G, Flock M, Frykberg L, Lannergård J, Flock J-I, Guss Bengt. Two novel IgG endopeptidases of Streptococcus equi.. FEMS Microbiol Lett 2009;298:44–50.
    doi: 10.1111/j.1574-6968.2009.01698.xpubmed: 19659725google scholar: lookup
  25. Robinson C, Waller AS, Frykbergb L, Flock M, Zachrisson O, Guss B. Intramuscular vaccination with Strangvac is safe and induces protection against equine strangles caused by Streptococcus equi.. Vaccine 2020;38:4861–4868.
    doi: 10.1016/j.vaccine.2020.05.046pubmed: 32507408google scholar: lookup
  26. Naegeli A, Bratanis E, Karlsson C, Shannon O, Kalluru R, Linder A. Streptococcus pyogenes evades adaptive immunity through specific IgG glycan hydrolysis.. J Exper Med 2019;216:1615–1629.
    pmc: PMC6605743pubmed: 31092533

Citations

This article has been cited 3 times.
  1. Borba KER, Legere RM, Canaday NM, Skrobarczyk JW, Arnold ZWT, Cotton-Betteridge E, Poveda C, Criscitiello MF, Bordin AI, Berghman LR, Pollet JBK, Cohen ND. Maternal Immunization with VP8* mRNA Vaccine Yields Superior Passive Transfer of Rotavirus-Neutralizing Antibodies to Foals. Vaccines (Basel) 2026 Jan 9;14(1).
    doi: 10.3390/vaccines14010076pubmed: 41600992google scholar: lookup
  2. Liu L, Cai P, Gu W, Duan X, Gao S, Ma X, Ma Y, Ma S, Li G, Wang X, Cai K, Wang Y, Cai T, Zhao H. Evaluation of vaccine candidates against Rhodococcus equi in BALB/c mice infection model: cellular and humoral immune responses. BMC Microbiol 2024 Jul 8;24(1):249.
    doi: 10.1186/s12866-024-03408-zpubmed: 38977999google scholar: lookup
  3. Friedrich B, Tietze R, Dümig M, Sover A, Boca MA, Schreiber E, Band J, Janko C, Krappmann S, Alexiou C, Lyer S. Magnetic Removal of Candida albicans Using Salivary Peptide-Functionalized SPIONs. Int J Nanomedicine 2023;18:3231-3246.
    doi: 10.2147/IJN.S409559pubmed: 37337577google scholar: lookup
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