title: Lack of correlation between BCG-induced tuberculin skin test sensitisation and protective immunity in cattle.
abstract: Vaccination of cattle with Mycobacterium bovis Bacille Calmette-Guérin (BCG) can provide significant protection against bovine tuberculosis (TB). However, BCG vaccination sensitises animals to respond to the tuberculin skin-test. This provides a potential operational impediment to the use of BCG as a cattle vaccine since the tuberculin skin-test is the primary surveillance tool used by many countries with 'test and slaughter' control strategies. Currently, it is also unclear what BCG-induced skin-test conversion means in respects to BCG's protective immunity. In the current study we first investigated the duration of tuberculin skin-test sensitisation in calves neonatally vaccinated with BCG. BCG vaccination induced strong skin-test responses in calves during their first 6 months. However, a rapid decay in skin-test sensitivity was observed after this time. Between 6 and 9 months this represented a reduction from 80% to 8% of calves providing a positive response in the single intradermal comparative cervical tuberculin test at standard interpretation. We next investigated the relationship between BCG induced skin-test sensitivity and retention of protective immunity. Calves were neonatally vaccinated with BCG and subsequently divided into 2 groups based on retention or loss of tuberculin skin-test responses after 6 months. In contrast to their skin-test responsiveness, these vaccinates maintained their tuberculin specific IFN-γ blood responses. Moreover, irrespective of their pre-challenge skin-test responses, following M. bovis challenge both groups of BCG vaccinated calves demonstrated comparable levels of protection, as evidenced by reduced TB-associated pathology. Therefore, we have demonstrated that following neonatal BCG vaccination of cattle, tuberculin skin-test responder frequencies waned rapidly after 6 months but importantly, loss of skin-test sensitivity did not correlate with loss of protective immunity. These findings could have implications for the practical application of BCG based cattle vaccines.
authors.affiliation: TB Research Group, Animal Health Veterinary Laboratory Agency-Weybridge, Woodham Lane, Addlestone, Surrey KT15 3NB, UK. Adam.Whelan@ahvla.gsi.gov.uk
authors.forename: A O
authors.initials: AO
authors.lastname: Whelan
authors.forename: M
authors.initials: M
authors.lastname: Coad
authors.forename: B L
authors.initials: BL
authors.lastname: Upadhyay
authors.forename: D J
authors.initials: DJ
authors.lastname: Clifford
authors.forename: R G
authors.initials: RG
authors.lastname: Hewinson
authors.forename: H M
authors.initials: HM
authors.lastname: Vordermeier
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D002417:Cattle; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D014374:Tuberculin Test; D014380:Tuberculosis, Bovine / Q000276:immunology* / Q000517:prevention & control*
chemical_list: D001500:BCG Vaccine; D007371:Interferon-gamma