Efficacy and clinical safety of pegbovigrastim for preventing naturally occurring clinical mastitis in periparturient primiparous and multiparous cows on US commercial dairies.

Periparturient dairy cows experience impaired immune function, exhibited as a transient decrease in neutrophil function. This decrease in immune competence is associated with an increase in susceptibility to bacterial infections, including mastitis and metritis. Bovine granulocyte colony stimulating factor (bG-CSF) is an endogenous protein that enhances neutrophil bactericidal functions and increases the production of neutrophils from bone marrow precursors. Administration of pegbovigrastim (recombinant bG-CSF covalently bound to polyethylene glycol) around the time of calving has been shown to reduce the incidence of new clinical mastitis cases in a natural disease model system. To further explore the application of pegbovigrastim under herd management systems typical of those found in the US dairy industry, we conducted a multicenter field study to evaluate the efficacy and clinical safety of pegbovigrastim administered to multiparous cows and heifers approximately 7 d before calving and within 24 h of calving. Responses of treated cows were compared with those of animals treated with sterile saline. Animals treated with pegbovigrastim exhibited 4- to 5-fold increases in circulating neutrophil numbers within 24 h of treatment initiation, and this increase persisted at least a week beyond the second dose. Pegbovigrastim-treated animals exhibited a 35% decrease in the incidence of clinical mastitis relative to the controls during the first 30 d of lactation. Animals treated with pegbovigrastim also exhibited a 52% reduction in failure to return to visual estrus within 80 d of calving. We observed no differences in somatic cell count or milk composition between treated and control animals. We also found no differences in the duration of pregnancy or proportion of viable calves in treated cows relative to control animals. These results indicate that administration of pegbovigrastim provides a well-tolerated, novel approach to overcoming periparturient immune suppression, resulting in reduced susceptibility to clinical mastitis during early lactation.

Efficacy of polyethylene glycol-conjugated bovine granulocyte colony-stimulating factor for reducing the incidence of naturally occurring clinical mastitis in periparturient dairy cows and heifers.

OBJECTIVE: To evaluate effects of various doses of polyethylene glycol (PEG)-conjugated bovine granulocyte colony-stimulating factor (bG-CSF) on the incidence of naturally occurring clinical mastitis in periparturient dairy cattle. ANIMALS: 211 periparturient Holstein cows and heifers. PROCEDURES: Approximately 7 days before the anticipated date of parturition (day of parturition = day 0), healthy cattle received SC injections of sterile saline (0.9% NaCl) solution (control treatment) or PEG-bG-CSF at 5, 10, or 20 µg/kg. Cattle were commingled and housed in a pen with dirt flooring, which was kept wet to maximize the incidence of naturally occurring clinical mastitis. Within 24 hours after parturition, each animal again received the assigned treatment. Mammary glands and milk were visually scored for abnormalities twice daily for 28 days after parturition. Milk samples were aseptically collected from mammary glands with an abnormal appearance or abnormal milk and submitted for microbial culture. Daily milk production was recorded, and milk composition was assessed on days 3, 5, 7, and 10. RESULTS: Cattle treated with PEG-bG-CSF at 10 and 20 µg/kg had significantly fewer cases of clinical mastitis (9/54 and 5/53, respectively), compared with control cattle (18/53). Administration of PEG -bG-CSF did not significantly affect daily milk production or milk composition. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that PEG-bG-CSF was effective for reducing the incidence of naturally occurring clinical mastitis in periparturient dairy cattle. Further investigations of the use of PEG-bG-CSF as a potential preventative intervention should be conducted.