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.
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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
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Hentrich, Karina
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Clinical Microbiology, Karolinska University Hospital, 171 76 Stockholm, Sweden.
Flock, Margareta
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Frosth, Sara
Department of Biomedical Science and Veterinary Public Health, Swedish University of Agricultural Sciences, 750 07 Uppsala, Sweden.
Jacobsson, Karin
Department of Biomedical Science and Veterinary Public Health, Swedish University of Agricultural Sciences, 750 07 Uppsala, Sweden.
Bjerketorp, Joakim
Department of Biomedical Science and Veterinary Public Health, Swedish University of Agricultural Sciences, 750 07 Uppsala, Sweden.
Pathak, Anuj
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Ido, Noela
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Henriques-Normark, Birgitta
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Clinical Microbiology, Karolinska University Hospital, 171 76 Stockholm, Sweden.
Frykberg, Lars
Department of Biomedical Science and Veterinary Public Health, Swedish University of Agricultural Sciences, 750 07 Uppsala, Sweden.
Paillot, Romain
Intervacc AB, 129 22 Stockholm, Sweden.
Guss, Bengt
Department of Biomedical Science and Veterinary Public Health, Swedish University of Agricultural Sciences, 750 07 Uppsala, Sweden.
Wood, Tim
Intervacc AB, 129 22 Stockholm, Sweden.
Flock, Jan-Ingmar
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Waller, Andrew Stephen
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.
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