Antibody Titres to Strangvac® Antigens Correlate with Protection and Duration of Immunity Against Experimental Infection with Streptococcus equi Subspecies equi

Background/Objectives: Strangles, caused by Streptococcus equi subspecies equi (S. equi), remains a common and severe equine infectious disease. Strangvac®, a recombinant fusion protein vaccine licenced in Europe, contains the antigens (Ag) CCE, Eq85, IdeE and a saponin adjuvant. Although its efficacy is high (94% in clinical trials and 100% in some natural outbreaks), immune correlates of protection have not been defined. This study determined the antibody (Ab) thresholds predictive of protection against clinical disease following high-dose experimental S. equi infection and the expected levels of protection at 6 and 12 months after V2. Methods: This study was a retrospective analysis of six independent double-blinded placebo-controlled experimental infection studies involving 129 ponies (80 vaccinated controls and 49 placebo controls) and a serology study (12 vaccinated ponies). Ponies received two to five vaccine doses before being experimentally challenged with S. equi strain Se4047. Ponies in the serology study were not experimentally infected. The onset of pyrexia (≥39 °C for at least 2 of 3 consecutive days, OOT) was used as a disease marker. Serology to IdeE, Eq85 and CCE was analysed with standardised clinical outcomes to define protective thresholds through correlation and Receiver Operating Characteristic (ROC) analyses. The predicted level of protection up to one year after V2 was then calculated (duration of immunity: DOI). Results: A protection threshold of ≥10 days to OOT, derived from the control distribution, was used for ROC modelling. Predictive performance (e.g., accuracy, precision, specificity) was calculated for individual and combined Ab thresholds. All controls developed pyrexia (median 6 days, IQR 5–7), with 46 out of 49 (93.9%) within 9 days of the challenge. Vaccinated ponies showed significantly delayed or absent OOT compared with controls (p < 0.0001), with 37 vaccinated ponies (46.25%) reaching the end of the studies without developing pyrexia. The Ab titre to all antigens was significantly associated with the level of protection (p < 0.0001). ROC analyses demonstrated high discriminative power (AUC 0.86–0.88). Optimal Ab titre boundaries yielded high precision (≥80%) for all Ags (IdeE: 3.5–4.3; Eq85: 2.65–3.7 and CCE: 2.66–3.2). Both precision and accuracy remained above 80% for levels of IdeE and Eq85 Ab titres superior or equal to those measured up to one year after V2, with an estimated level of protection of 78.9% to 81.2% in vaccinated animals. Conclusions: Ab titres to all three Ags represent robust correlates of protection against pyrexia following high-dose experimental S. equi challenge in Strangvac®-vaccinated ponies. Ab titres measured up to one year after V2 were estimated to continue to provide significant protection in vaccinated animals. These findings support the observed levels of protection conferred by Strangvac® against natural infection with S. equi.