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Equine veterinary journal2026; doi: 10.1002/evj.70200

Cross-protective effect of a multicomponent fusion protein vaccine during a natural episode of Streptococcus zooepidemicus respiratory disease in ponies.

Abstract: Streptococcus equi subspecies zooepidemicus is a highly diverse opportunistic pathogen of horses, associated with respiratory disease and endometritis. Objective: To characterise S. zooepidemicus isolates recovered from young ponies during a natural episode of respiratory disease, and to determine if vaccination with Strangvac®, a vaccine against Streptococcus equi subspecies equi, conferred cross-protection. Methods: Retrospective analysis of a double-blinded placebo-controlled study involving 32 ponies (16 vaccinates and 16 placebo controls) that experienced a natural episode of respiratory disease around the time of second vaccination. Methods: Ponies were monitored daily for clinical signs of respiratory infection. Nasopharyngeal swabs were taken from affected animals to identify equine pathogens by qPCR and culture. The genomes of 23 S. zooepidemicus isolates were sequenced. Clinical and serological differences between vaccine and placebo groups were determined. Results: The clinical samples were positive for equine herpes virus-4 or S. zooepidemicus (1/15 [7%] and 13/15 [87%], respectively). Seven different S. zooepidemicus sequence types, which encoded between four and seven of the eight antigens in Strangvac® with ≥70% amino acid identity, were recovered from affected horses. The most conserved antigens were CNE, EAG, Eq5 and IdeE. The number of days that ponies had a cough was significantly associated (p = 0.005) with the vaccination status, with fewer days in the vaccinated compared to co-mingled control ponies (1.8 ± 1.9 days vs. 3.4 ± 3.5 days). A higher antibody titre to IdeE immediately prior to second vaccination correlated with a lower cumulative coughing score (p = 0.03). A reduced number of days with abnormal temperature correlated with increased antibody levels against Eq85 (p = 0.023-0.028). Conclusions: Small group size. Conclusions: This study provides evidence in support of a cross-protective effect of Strangvac® for the reduction of clinical signs associated with natural infection with S. zooepidemicus, which correlated with the presence of higher antibody titres to IdeE and Eq85.
Publication Date: 2026-06-02 PubMed ID: 42231549DOI: 10.1002/evj.70200Google Scholar: Lookup
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  • Journal Article

Summary

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Overview

  • This study investigated whether vaccination with Strangvac®, a vaccine designed for Streptococcus equi subspecies equi, offers cross-protection against respiratory disease caused by Streptococcus zooepidemicus in ponies.
  • The research involved analyzing clinical signs, pathogen presence, genetic relatedness of bacterial strains, and antibody responses in vaccinated versus unvaccinated ponies during a natural outbreak.

Background

  • Pathogen: Streptococcus equi subspecies zooepidemicus (S. zooepidemicus) is an opportunistic bacterial pathogen in horses, known to cause respiratory infections and reproductive issues such as endometritis.
  • Diversity: S. zooepidemicus is genetically diverse, making it challenging to target with vaccines developed against related pathogens such as Streptococcus equi subspecies equi (S. equi).
  • Vaccine: Strangvac® is a multicomponent fusion protein vaccine developed against S. equi, targeting eight specific antigens.
  • Objective: To determine if Strangvac® can provide cross-protection against S. zooepidemicus during a naturally occurring respiratory disease outbreak in ponies.

Study Design and Methods

  • Study type: Retrospective analysis of a double-blinded placebo-controlled trial.
  • Subjects: 32 young ponies split evenly into 16 vaccinated with Strangvac® and 16 receiving placebo.
  • Timing: The natural respiratory disease outbreak occurred around the time of the ponies’ second vaccination dose.
  • Clinical monitoring: Ponies were observed daily for respiratory symptoms, particularly coughing and abnormal body temperature.
  • Pathogen detection: Nasopharyngeal swabs from symptomatic ponies were tested by quantitative PCR (qPCR) and bacterial culture to identify causative agents.
  • Genomic analysis: Whole genome sequencing was performed on 23 S. zooepidemicus isolates obtained from the affected ponies to determine strain diversity and antigenic similarity to vaccine components.
  • Immune response analysis: Antibody levels against vaccine antigens were measured and compared with clinical outcomes.

Key Findings

  • Pathogen prevalence: Among 15 tested symptomatic ponies, equine herpes virus-4 was detected in 7% of samples, whereas S. zooepidemicus was detected in 87%.
  • Genetic diversity: Seven distinct sequence types of S. zooepidemicus were identified, showing varying levels (70% or greater amino acid identity) of homology to the eight antigens in Strangvac®.
  • Antigen conservation: The antigens CNE, EAG, Eq5, and IdeE were the most conserved across the isolated strains.
  • Clinical outcomes: Vaccinated ponies experienced significantly fewer coughing days (average 1.8 days) compared to placebo ponies (average 3.4 days), with a p-value of 0.005 indicating statistical significance.
  • Immune correlates of protection: Higher antibody titers against the IdeE antigen before the second vaccination were associated with a lower cumulative cough score (p=0.03). Similarly, increased antibodies against Eq85 correlated with fewer days of abnormal temperature (p=0.023-0.028).

Interpretation and Implications

  • Cross-protection evidence: Despite vaccine targeting S. equi, Strangvac® showed cross-protective benefits against S. zooepidemicus infections in ponies, reducing severity and duration of respiratory symptoms.
  • Antigen relevance: The conserved vaccine antigens, especially IdeE and Eq85, may play a crucial role in protective immunity, suggesting these components are important even in genetically diverse S. zooepidemicus strains.
  • Immune response monitoring: Antibody levels to specific vaccine antigens can serve as indicators of clinical protection and could guide future vaccine improvements or usage protocols.
  • Limitations: The study had a small sample size and retrospective design, which may impact generalizability and the strength of conclusions.

Conclusions

  • The study provides supportive evidence that Strangvac® vaccination confers cross-protective benefits against natural S. zooepidemicus respiratory infection in ponies, as shown by reduced coughing and fever duration.
  • The correlation between antibody titers to IdeE and Eq85 antigens and improved clinical outcomes highlights potential targets for further vaccine optimization.
  • These findings may influence equine respiratory disease prevention strategies, suggesting that existing vaccines designed for related pathogens can have broader protective roles.

Cite This Article

APA
Paillot R, Newton JR, Gonzalez Medina S, Frosth S, Frykberg L, Flock M, Guss B, Flock JI, Waller AS. (2026). Cross-protective effect of a multicomponent fusion protein vaccine during a natural episode of Streptococcus zooepidemicus respiratory disease in ponies. Equine Vet J. https://doi.org/10.1002/evj.70200

Publication

ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English

Researcher Affiliations

Paillot, Romain
  • Intervacc AB, Stockholm, Sweden.
Newton, J Richard
  • Equine Infectious Disease Surveillance (EIDS), Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
Gonzalez Medina, Sonia
  • CVS Equine Division, Endell Equine Hospital, Salisbury, UK.
Frosth, Sara
  • Department of Animal Biosciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Frykberg, Lars
  • Department of Animal Biosciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Flock, Margareta
  • Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden.
Guss, Bengt
  • Department of Animal Biosciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Flock, Jan-Ingmar
  • Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden.
Waller, Andrew S
  • Intervacc AB, Stockholm, Sweden.

Grant Funding

  • Intervacc AB

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