VANGUARD®crLyme: A next generation Lyme disease vaccine that prevents B. burgdorferi infection in dogs.

Lyme disease, a public health threat of significance to both veterinary and human medicine, is caused by the tick (Ixodes) transmitted spirochete, Borreliella burgdorferi. Here we report on the immunogenicity and efficacy of VANGUARD®crLyme (Zoetis), the most recent canine Lyme disease vaccine to be approved by the United States Department of Agriculture. VANGUARD®crLyme is a subunit vaccine consisting of outer surface protein A (OspA) and a recombinant outer surface protein C (OspC) based-chimeric epitope protein (chimeritope) that consists of at least 14 different linear epitopes derived from diverse OspC proteins. The combination of OspA and the OspC chimeritope (Ch14) in the vaccine formulation allows for the development of humoral immune responses that work synergistically to target spirochetes in both ticks and in mammals. Immunogenicity was assessed in purpose-bred dogs. A two-dose vaccination protocol resulted in high antibody titers to OspA and Ch14 and vaccinal antibody reacted with 25 different recombinant OspC variants. Efficacy was demonstrated using an Ixodes scapularis -purpose bred dog challenge model. Vaccination with VANGUARD®crLyme provided protection against infection and prevented the development of clinical manifestations and histopathological changes associated with Lyme disease.

Field safety study of VANGUARD®crLyme: A vaccine for the prevention of Lyme disease in dogs.

Here we report the results of a large-scale pre-license safety study in which two serials of VANGUARD®crLyme, a vaccine for canine Lyme disease, were tested in its target population (dogs) under the conditions of its intended use. Six-hundred and twenty dogs, from three distinct geographic regions of the United States were enrolled in this study with each receiving two doses of vaccine by subcutaneous injection 3 to 4 weeks apart. Approximately one-third of the dogs were of minimum age (≤8 weeks of age) to meet regulatory requirements. Safety was evaluated by observation of local and systemic reactions for at least 10 days after each vaccination. Abnormal health events (AHEs) occurred at low frequencies and no serious AHEs were observed. The results demonstrated that VANGUARD®crLyme is safe for use in healthy dogs 8 weeks of age or older.

A blinded, randomized, placebo-controlled trial of the safety of lokivetmab (ZTS-00103289), a caninized anti-canine IL-31 monoclonal antibody in client-owned dogs with atopic dermatitis.

BACKGROUND: Lokivetmab (ZTS-00103289) is a caninized anti-canine IL-31 monoclonal antibody that has demonstrated efficacy in reducing pruritus associated with atopic dermatitis (AD) in dogs in field trials. HYPOTHESIS/OBJECTIVES: This study evaluated the safety of lokivetmab in a randomized, double blind, placebo-controlled trial in client owned dogs with AD with minimal restrictions on concomitant medications and co-morbidities. ANIMALS: Clinicians at 14 veterinary clinics enrolled client owned dogs (n = 245) with chronic AD. METHODS: Dogs were randomized at a 2:1 ratio to receive either lokivetmab (1.0-3.3 mg/kg) or placebo administered subcutaneously on days 0 and 28. Clinicians examined dogs, and collected blood and urine for assessment of clinical pathology and immunogenicity (days 0, 28 and 42). RESULTS: There were no immediate hypersensitivity reactions (e.g. wheals, vomiting). Discomfort at administration occurred in 5.1% of dogs and was similar in frequency and severity between lokivetmab- and placebo-treated groups. Pruritus was reported as an adverse event during the study less frequently in the lokivetmab-treated group (4.9% and 19.3%, respectively); otherwise, adverse events occurred at a similar frequency between treatment groups. There were no clinically important differences between groups in clinical pathology results. Treatment-induced immunogenicity was found in 2.5% of lokivetmab treated dogs. A wide variety of concomitant medications were used with no clinically apparent adverse interactions. CONCLUSIONS AND CLINICAL IMPORTANCE: Among a diverse population of 162 client owned dogs with a clinical diagnosis of AD, treatment with two monthly doses of lokivetmab was safe, based on observed adverse events and clinical pathology results over a 42 day period.

A blinded, randomized, placebo-controlled, dose determination trial of lokivetmab (ZTS-00103289), a caninized, anti-canine IL-31 monoclonal antibody in client owned dogs with atopic dermatitis.

BACKGROUND: Pruritus is the hallmark clinical sign of atopic dermatitis (AD) in dogs. Lokivetmab, a caninized anti-canine IL-31 monoclonal antibody, reduced pruritus and associated inflammatory skin lesions in a proof-of-concept study in dogs with AD. HYPOTHESIS/OBJECTIVES: The objective was to describe lokivetmab dose response in a randomized, double blind, placebo-controlled trial. ANIMALS: Clinicians at 15 referral clinics enrolled 211 client owned dogs with a history of chronic AD. METHODS: Dogs were randomized to treatment with lokivetmab (0.125, 0.5 or 2.0 mg/kg) or placebo administered subcutaneously once on Day 0. Dog owners assessed visual analog scale (VAS) scores of pruritus on days 0, 1, 2, 3, 7, 14, 21, 28, 35, 42, 49 and 56. Clinicians assessed Canine AD Extent and Severity Index (CADESI-03) scores on days 0, 7, 14, 28, 42 and 56. RESULTS: Treatment with lokivetmab (2 mg/kg) resulted in a greater percentage reduction from baseline in owner assessed pruritus (days 1-49) and clinician assessed CADESI-03 scores (days 7-56) compared to placebo (P < 0.05); differences were achieved in lower dose groups but at later time points and for shorter duration for both owner assessed pruritus (0.5 mg/kg, days 2-35; 0.125 mg/kg, days 7-21) and clinician assessed CADESI-03 scores (0.5 mg/kg and 0.125 mg/kg, Day 14). CONCLUSIONS AND CLINICAL IMPORTANCE: Lokivetmab (0.5, 2.0 mg/kg) reduced pruritus compared to placebo for at least 1 month. Level and duration of response increased with increasing dose. Further studies are needed to better understand variability in individual responses across a broader population of dogs with AD.