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Cattle BCG: Duration of immunity at minimum vaccine dose titre - SE3334

Bovine tuberculosis (BTB) is one of the most pressing animal health problems in the UK.
• The government’s primary BTB research goal is to develop a deployable cattle BTB vaccine within the next five years.
• An authorised vaccine supported by an authorised “Differentiating Infected from Vaccinated Animals” (DIVA) test is expected to be a strong additional tool to help eradicate BTB in those parts of the country where the disease is endemic.
• The available candidate vaccine (CattleBCG) is the same strain and presentation as the Bacillus Calmette–Guérin (BCG) authorised for use in humans and badgers (BCG Danish SSI strain 1331).
• The aim is to develop a deployable cattle BTB vaccine within the next five years. To achieve this goal, it is imperative to secure the necessary marketing authorisations (MAs) for both the vaccine and a DIVA test. The Veterinary Medicines Directorate (VMD) is responsible for assessing MA applications to ensure the safety, quality and efficacy of veterinary medicines in the UK.
• APHA has submitted applications to VMD to conduct field trials of the CattleBCG and DST-F. These applications (Animal Test Certificates) have been granted and the initiation of field trials is imminent.
• One requirement for an MA application is to define the duration of immunity of CattleBCG at the minimum vaccine titer to be proposed in the MA.
• The first 1-year DOI study performed at the Institute of Animal Health between 2006 and 2007, was not a regulatory study and although efficacy was demonstrated, the vaccine was not titrated at time of use. The VMD will therefore only accept the official Statens Serum Institut (vaccine producer at that time) release titer from the batch used in that study to set a minimum dose of 3.2 x 106 CFU CattleBCG.
• This dose is close to the upper dose range we propose and have conducted safety studies for (1-4 x 106 CFU, which is the same as the human BCG production line).
• Using the same dose range enables us to use the BCG from the human vaccine production line (with a different label) without the need to prepare bespoke CattleBCG preparations, which significantly reduces cost. However, a minimum batch release dose of 3.2 x 106 CFU would impose significant operational restrictions or even a specific production line and substantially higher product costs.
• Therefore, this study proposes a pivotal DOI study to provide critical data demonstrating the efficacy of CattleBCG at the minimum proposed dose of 106 CFU to support indications and claims in the Specific Product Characteristics document (SPC) to be included in the MA application dossier.
• Not performing a pivotal DOI study now, carries significant risk of increased production and supply costs for CattleBCG, necessity for additional studies and a substantial delay of the timeline to licensure and availability of a deployable cattle TB vaccine. It also brings additional risk in maintaining capability of the expertise within APHA
Overall aim: To define the duration of immunity of CattleBCG in calves vaccinated with the minimum titer for which we seek licensure (1 x 106 CFU).

Specific objectives are:
Objective 1: To perform DOI experiment.
Objective 2: To undertake informative studies to investigate host responses post-vaccination and post-challenge.
Objective 3: Contribution of biological samples to APHA TB Bio-archive.
Time-Scale and Cost
From: 2021

To: 2023

Cost: £1,305,454
Contractor / Funded Organisations
APHA (Animal and Plant Health Agency)