The bovine and human respiratory syncytial viruses cause severe lower respiratory tract infections. Effective vaccines against the respiratory syncytial viruses have been lacking since vaccine failures in the 1960s and 1970s. In this report, we describe a bovine respiratory syncytial virus (bRSV) challenge model in which both classical bRSV respiratory infection and vaccine-enhanced immune pathology were reproduced. The classical, formalin-inactivated (FI) bRSV vaccine that has been associated with vaccine failure was efficient in inducing high antibody titers and reducing viral loads but also primed calves for a far more serious enhanced respiratory disease after a bRSV challenge, thereby mimicking the enhanced clinical situation in FI human RSV (hRSV)-immunized and hRSV-infected infants in the 1960s. We show that immunization with FI-bRSV mainly primes a Th2-like inflammatory response that is characterized by a significant eosinophilic influx in the bronchial alveolar lung fluid and lung tissues and high levels of immunoglobulin E serum antibodies. The current model may be useful in the evaluation of new bRSV candidate vaccines for potency and safety.

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Serial peri-operative plasma and serum samples from 55 horses suffering from acute abdominal disease and presented for surgical intervention were assayed for the presence of endotoxins (lipopolysaccharides; LPS), tumor necrosis factor (TNF) and interleukin-6 (IL-6). At study entry, venous blood was collected for blood cultures. Intra-operatively collected ascitic fluid samples were assayed for the presence of LPS. The clinical course of the disease was documented. Four horses were excluded from the study. At study entry, 21 of the 51 horses (41%) had increased platelet-rich plasma LPS concentrations, i.e. ≥ 5 ng/l (mean 35.5; range 7-197 ng/l), in 34 horses (67%) IL-6 concentrations were increased, i.e. exceeding 35 ng/l (mean 364; range 36—1762 ng/l). Detectable TNF was present in 5 horses (10%); 3 of them died spontaneously during surgery. In all TNF positive samples, markedly increased LPS and IL-6 concentrations were detected. Study entry IL-6 concentrations were significantly higher in non-surviving (mean 394; range < 20—1762 ng/l) than in surviving horses (mean 116; range < 20—894 ng/l; P < 0.0002). This was most evident when non-surviving horses with inflamed bowel disease were considered (mean 1096; range 650—1762 ng/l; P < 0.0001). Positive ascitic fluid LPS concentrations (≥ 3 ng/l) were encountered in 18 horses. There was no significant correlation between the LPS concentrations in ascites and plasma. Study entry concentrations of IL-6 were significantly correlated with LPS concentrations (r = 0.62; P < 0.001) and were inversely correlated with platelet counts (r = -0.46; P < 0.002). The magnitude of a calculated LPS-cytokine score strongly correlated with mortality (P < 0.001). Receiver operating characteristic (ROC) curve analysis showed that the IL-6 assay had reasonable accuracy for the prediction of unfavorable outcome (i.e. the area under the curve equalled 0.72), in contrast to the LPS assay. The results indicate that LPS, TNF and IL-6 are predominantly released in the systemic circulation of horses suffering from inflamed and ischemic bowel disease. IL-6 concentrations have predictive value for unfavorable outcome and the simultaneous presence of increased LPS, TNF and IL-6 concentrations is especially associated with a poor clinical condition and outcome.The clinical signs culminating in equine acute abdominal disease range widely, from mild symptoms to fulminant shock with profound metabolic and respiratory acidosis, hypotension, and hypovolemia with death ocat RYERSON UNIV on June 18, 2015 ini.sagepub.com Downloaded from

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