Neutralisation of the Immunoglobulin-Cleaving Activity of Streptococcus equi Subspecies equi IdeE by Blood Sera from Ponies Vaccinated with a Multicomponent Protein Vaccine.
Abstract: subspecies () is the cause of strangles, one of the most prevalent diseases of horses worldwide. The disease is characterised by fever and the formation of abscesses in the lymph nodes of the head and neck, which can restrict the airway. A multicomponent subunit vaccine, Strangvac, has been shown to effectively reduce clinical signs of strangles and to reduce its incidence. The aim of this study was to determine the immune response against the immunoglobulin-cleaving endopeptidase IdeE, a key protective component within the vaccine and the ability of antibodies to neutralize the proteolytic activity of IdeE. An in vitro assay was developed to measure the functional inhibition of recombinant IdeE by horse sera pre- and post-vaccination. The IdeE-neutralising titres were compared to the corresponding IdeE-specific antibody titres measured by iELISA (indirect Enzyme-Linked Immunosorbent Assay). A significant IdeE-specific antibody response in blood serum collected from ponies was induced after Strangvac vaccinations. Concomitantly, significant increases in the neutralising activity of IdeE occurred, persisting for at least 12 months post-second vaccination. IdeE-neutralising activity was further increased significantly after a third vaccination, even when the third dose was administered 12 months after the second dose, demonstrating that immunological memory to the vaccine persisted for 12 months. There was a significant correlation between the IdeE-neutralising activity of blood sera and the level of IdeE-specific antibodies. These data provide insights into one potential mechanism by which this vaccine protects Equids against or during infection.
Publication Date: 2025-10-17 PubMed ID: 41150447PubMed Central: PMC12568127DOI: 10.3390/vaccines13101061Google Scholar: Lookup
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- Journal Article
Summary
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Overview
- This study investigates how a vaccine for horses stimulates the immune system to produce antibodies that neutralize an enzyme, IdeE, produced by the bacteria Streptococcus equi subspecies equi, the cause of the disease strangles.
- The research shows that vaccinated ponies generate antibodies that block the activity of IdeE, potentially explaining how the vaccine protects horses from this illness.
Background
- Strangles disease: Caused by Streptococcus equi subspecies equi, this disease is common worldwide in horses and is characterized by fever and abscess formation in lymph nodes of the head and neck, which may block airways.
- Role of IdeE: IdeE is an immunoglobulin-cleaving endopeptidase enzyme produced by the bacteria, which helps it evade the horse’s immune system by breaking down antibodies.
- Vaccination: Strangvac is a multicomponent subunit vaccine designed to protect horses against strangles by targeting multiple bacterial components, including IdeE.
Aims of the Study
- To measure the immune response generated against IdeE after vaccination with Strangvac.
- To evaluate whether antibodies produced can neutralize the enzymatic activity of IdeE, preventing it from cleaving immunoglobulins.
Methods
- An in vitro assay was developed to test the ability of recombinant IdeE enzyme to be inhibited by pony blood serum collected before and after vaccination.
- Antibody levels specific to IdeE were measured using indirect ELISA (iELISA) to quantify the immune response.
- Neutralising activity (ability to block IdeE function) in sera was compared to antibody titres to establish correlation.
Key Findings
- Vaccination with Strangvac induced a significant increase in IdeE-specific antibodies in ponies’ blood serum compared to before vaccination.
- There was a corresponding increase in serum’s ability to neutralize the IdeE enzyme’s activity, indicating functional effectiveness of the antibodies.
- This neutralizing activity was sustained for at least 12 months following the second vaccination, suggesting lasting immunity.
- A third vaccination, even when administered 12 months after the second, further increased neutralizing activity, highlighting persistent immunological memory.
- A strong statistical correlation was found between the antibody levels (measured by iELISA) and the ability to neutralize IdeE.
Implications
- The study elucidates an important mechanism of protection offered by Strangvac: antibodies that prevent IdeE from destroying the horse’s protective immunoglobulins.
- This blocking of IdeE helps maintain effective immunity during infection, reducing disease severity or incidence.
- It supports the use of booster vaccinations to sustain long-term immunity in horses against strangles.
- The assay developed provides a functional test of vaccine-induced immunity that could be useful for future vaccine evaluation and improvement.
Cite This Article
APA
Righetti F, Hentrich K, Flock M, Frosth S, Jacobsson K, Bjerketorp J, Pathak A, Ido N, Henriques-Normark B, Frykberg L, Paillot R, Guss B, Wood T, Flock JI, Waller AS.
(2025).
Neutralisation of the Immunoglobulin-Cleaving Activity of Streptococcus equi Subspecies equi IdeE by Blood Sera from Ponies Vaccinated with a Multicomponent Protein Vaccine.
Vaccines (Basel), 13(10), 1061.
https://doi.org/10.3390/vaccines13101061 Publication
Researcher Affiliations
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
- Clinical Microbiology, Karolinska University Hospital, 171 76 Stockholm, Sweden.
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
- Department of Biomedical Science and Veterinary Public Health, Swedish University of Agricultural Sciences, 750 07 Uppsala, Sweden.
- Department of Biomedical Science and Veterinary Public Health, Swedish University of Agricultural Sciences, 750 07 Uppsala, Sweden.
- Department of Biomedical Science and Veterinary Public Health, Swedish University of Agricultural Sciences, 750 07 Uppsala, Sweden.
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
- Clinical Microbiology, Karolinska University Hospital, 171 76 Stockholm, Sweden.
- Department of Biomedical Science and Veterinary Public Health, Swedish University of Agricultural Sciences, 750 07 Uppsala, Sweden.
- Intervacc AB, 129 22 Stockholm, Sweden.
- Department of Biomedical Science and Veterinary Public Health, Swedish University of Agricultural Sciences, 750 07 Uppsala, Sweden.
- Intervacc AB, 129 22 Stockholm, Sweden.
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
- Department of Biomedical Science and Veterinary Public Health, Swedish University of Agricultural Sciences, 750 07 Uppsala, Sweden.
- Intervacc AB, 129 22 Stockholm, Sweden.
Grant Funding
- Intervacc AB
Conflict of Interest Statement
A.S.W. and R.P. are employed by Intervacc AB. T.W. is a former employee of Intervacc AB. B.G. and J.-I.F. are founders and former board members of Intervacc AB. F.R., K.H., M.F., S.F., K.J., J.B., A.P., N.I., B.H.-N., L.F. and B.G. have received research grants from Intervacc AB. None of the authors has any other financial or personal relationships that could inappropriately influence or bias the content of the paper.
References
This article includes 30 references
- Boyle A.G., Timoney J.F., Newton J.R., Hines M.T., Waller A.S., Buchanan B.R. Streptococcus equi Infections in Horses: Guidelines for Treatment, Control, and Prevention of Strangles-Revised Consensus Statement. J. Vet. Intern. Med. 2018;32:633–647. doi: 10.1111/jvim.15043.
- Chhabra D., Bhatia T., Goutam U., Manuja A., Kumar B. Strangles in Equines: An Overview. Microb. Pathog. 2023;178:106070. doi: 10.1016/j.micpath.2023.106070.
- Boyle A. Streptococcus equi Subspecies equi Infection (Strangles) in Horses. Compend. Contin. Educ. Vet. 2011;33:E1–E7.
- van Maanen K., van den Wollenberg L., de Haan T., Frippiat T. Epidemiology of Infectious Pathogens in Horses with Acute Respiratory Disease, Abortion, and Neurological Signs: Insights Gained from the Veterinary Surveillance System for Horses in The Netherlands (SEIN) Vet. Sci. 2025;12:567. doi: 10.3390/vetsci12060567.
- Timoney J.F. Strangles. Vet. Clin. N. Am. Equine Pract. 1993;9:365–374. doi: 10.1016/S0749-0739(17)30403-0.
- Newton J.R., Verheyen K., Talbot N.C., Timoney J.F., Wood J.L., Lakhani K.H., Chanter N. Control of Strangles Outbreaks by Isolation of Guttural Pouch Carriers Identified Using PCR and Culture of Streptococcus equi. Equine Vet. J. 2000;32:515–526. doi: 10.2746/042516400777584721.
- Newton J.R., Wood J.L., Dunn K.A., DeBrauwere M.N., Chanter N. Naturally Occurring Persistent and Asymptomatic Infection of the Guttural Pouches of Horses with Streptococcus equi. Vet. Rec. 1997;140:84–90. doi: 10.1136/vr.140.4.84.
- Verheyen K., Newton J.R., Talbot N.C., de Brauwere M.N., Chanter N. Elimination of Guttural Pouch Infection and Inflammation in Asymptomatic Carriers of Streptococcus equi. Equine Vet. J. 2000;32:527–532. doi: 10.2746/042516400777584703.
- Pringle J., Storm E., Waller A., Riihimäki M. Influence of Penicillin Treatment of Horses with Strangles on Seropositivity to Streptococcus equi ssp. equi-Specific Antibodies. J. Vet. Intern. Med. 2020;34:294–299. doi: 10.1111/jvim.15668.
- Morris E.R.A., Hillhouse A.E., Konganti K., Wu J., Lawhon S.D., Bordin A.I., Cohen N.D. 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.2020.108638.
- Waller A.S. New Perspectives for the Diagnosis, Control, Treatment, and Prevention of Strangles in Horses. Vet. Clin. N. Am. Equine Pract. 2014;30:591–607. doi: 10.1016/j.cveq.2014.08.007.
- Robinson C., Waller A.S., Frykberg L., Flock M., Zachrisson O., Guss B., Flock J.-I. 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.2020.05.046.
- Rendle D., Bowen M., Cavalleri J., De Brauwere N., Grondahl G., van Maanen K., Newton J.R. Strangles Vaccination: A Current European Perspective. Equine Vet. Educ. 2025;37:90–97. doi: 10.1111/eve.14032.
- Robinson C., Frykberg L., Flock M., Guss B., Waller A.S., Flock J.-I. Strangvac: A Recombinant Fusion Protein Vaccine That Protects Against Strangles, Caused by Streptococcus equi. Vaccine. 2018;36:1484–1490. doi: 10.1016/j.vaccine.2018.01.030.
- 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.x.
- Hulting G., Flock M., Frykberg L., Lannergård J., Flock J.-I., Guss B. Two Novel IgG Endopeptidases of Streptococcus equi. FEMS Microbiol. Lett. 2009;298:44–50. doi: 10.1111/j.1574-6968.2009.01698.x.
- Guss B., Flock M., Frykberg L., Waller A.S., Robinson C., Smith K.C., Flock J.-I. Getting to Grips with Strangles: An Effective Multi-Component Recombinant Vaccine for the Protection of Horses from Streptococcus equi Infection. PLoS Pathog. 2009;5:e1000584. doi: 10.1371/journal.ppat.1000584.
- Mitchell C., Steward K.F., Charbonneau A.R.L., Walsh S., Wilson H., Timoney J.F., Wernery U., Joseph M., Craig D., van Maanen K., et al. Globetrotting Strangles: The Unbridled National and International Transmission of Streptococcus equi Between Horses. Microb. Genom. 2021;7:mgen000528. doi: 10.1099/mgen.0.000528.
- Prion S., Haerling K.A. Making Sense of Methods and Measurement: Pearson Product-Moment Correlation Coefficient. Clin. Simul. Nurs. 2014;10:587–588. doi: 10.1016/j.ecns.2014.07.010.
- Galan J.E., Timoney J.F. Mucosal Nasopharyngeal Immune Responses of Horses to Protein Antigens of Streptococcus equi. Infect. Immun. 1985;47:623–628. doi: 10.1128/iai.47.3.623-628.1985.
- Hamlen H.J., Timoney J.F., Bell R.J. Epidemiologic and Immunologic Characteristics of Streptococcus equi Infection in Foals. J. Am. Vet. Med. Assoc. 1994;204:768–775. doi: 10.2460/javma.1994.204.05.768.
- Lei B., DeLeo F.R., Reid S.D., Voyich J.M., Magoun L., Liu M., Braughton K.R., Ricklefs S., Hoe N.P., Cole R.L., et al. Opsonophagocytosis-Inhibiting Mac Protein of Group a Streptococcus: Identification and Characteristics of Two Genetic Complexes. Infect. Immun. 2002;70:6880–6890. doi: 10.1128/IAI.70.12.6880-6890.2002.
- von Pawel-Rammingen U., Johansson B.P., Björck L. IdeS, a Novel Streptococcal Cysteine Proteinase with Unique Specificity for Immunoglobulin G. EMBO J. 2002;21:1607–1615. doi: 10.1093/emboj/21.7.1607.
- von Pawel-Rammingen U., Björck L. IdeS and SpeB: Immunoglobulin-Degrading Cysteine Proteinases of Streptococcus pyogenes. Curr. Opin. Microbiol. 2003;6:50–55. doi: 10.1016/S1369-5274(03)00003-1.
- Frick I.-M., Happonen L., Wrighton S., Nordenfelt P., Björck L. IdeS, a Secreted Proteinase of Streptococcus pyogenes, Is Bound to a Nuclease at the Bacterial Surface Where It Inactivates Opsonizing IgG Antibodies. J. Biol. Chem. 2023;299:105345. doi: 10.1016/j.jbc.2023.105345.
- Akesson P., Moritz L., Truedsson M., Christensson B., von Pawel-Rammingen U. IdeS, a Highly Specific Immunoglobulin G (IgG)-Cleaving Enzyme from Streptococcus pyogenes, Is Inhibited by Specific IgG Antibodies Generated During Infection. Infect. Immun. 2006;74:497–503. doi: 10.1128/IAI.74.1.497-503.2006.
- Shaw H.A., Remmington A., McKenzie G., Winkel C., Mawas F. Mucosal Immunization Has Benefits over Traditional Subcutaneous Immunization with Group A Streptococcus Antigens in a Pilot Study in a Mouse Model. Vaccines. 2023;11:1724. doi: 10.3390/vaccines11111724.
- Shaw H.A., Ozanne J., Burns K., Mawas F. Multicomponent Vaccines against Group A Streptococcus Can Effectively Target Broad Disease Presentations. Vaccines. 2021;9:1025. doi: 10.3390/vaccines9091025.
- Rieckmann K., Seydel A., Klose K., Alber G., Baums C.G., Schütze N. Vaccination with the Immunoglobulin M-Degrading Enzyme of Streptococcus suis, IdeSsuis, Leads to Protection against a Highly Virulent Serotype 9 Strain. Vaccine X. 2019;3:100046. doi: 10.1016/j.jvacx.2019.100046.
- Timoney J.F., Yang J., Liu J., Merant C. IdeE Reduces the Bactericidal Activity of Equine Neutrophils for Streptococcus equi. Vet. Immunol. Immunopathol. 2008;122:76–82. doi: 10.1016/j.vetimm.2007.10.017.
Citations
This article has been cited 1 times.- Rask E, Righetti F, Ruiz A, Bjerketorp J, Frosth S, Frykberg L, Jacobsson K, Guss B, Flock JI, Henriques-Normark B, Hartman E, Gustafsson A, Paillot R, Waller AS. Closing the Stable Door on Strangles: Serological Responses of Vaccinated Horses on a Farm Following the Arrival of a New Horse.. Animals (Basel) 2025 Dec 13;15(24).
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