title: Revaccination of cattle with bacille Calmette-Guérin two years after first vaccination when immunity has waned, boosted protection against challenge with Mycobacterium bovis.
abstract: In both humans and animals, controversy exists concerning the duration of protection induced by BCG vaccine against tuberculosis (TB) and whether revaccination enhances protection. A long-term study was undertaken to determine whether BCG-vaccinated calves would be protected against challenge with Mycobacterium bovis 2½ years after vaccination and to determine the effect of revaccination after 2 years. Seventy-nine calves were divided into five groups (n = 15-17 calves/group) with four of the groups vaccinated subcutaneously with 105 CFU of BCG Danish at 2-4 weeks of age and the fifth group serving as non-vaccinated controls. Three of the four BCG-vaccinated groups were revaccinated 2 years after the initial vaccination. One BCG-vaccinated group was revaccinated with BCG. A second group was vaccinated subcutaneously with a TB protein vaccine consisting of biopolyester particles (Biobeads) displaying two mycobacterial proteins, ESAT-6 and Antigen 85A, mixed with an adjuvant. A third group was vaccinated with TB proteins from M. bovis culture filtrate, mixed with an adjuvant. Twenty-three weeks after the BCG revaccination, all animals were challenged endotracheally with virulent M. bovis and a further 13 weeks later, animals were killed and necropsied to determine protection against TB. The BCG-vaccinated animals produced positive tuberculin caudal fold intradermal (15 of 62 animals) and IFN-γ TB test responses (six of 62 animals) at 6 months after vaccination, but not at subsequent time-points compared to the non-vaccinated animals. Calves receiving a single vaccination with BCG vaccine 2½ years prior to challenge were not protected against TB, while those revaccinated with BCG 2 years after the initial vaccination displayed significant reductions in lung and pulmonary lymph node lesion scores compared to the non-vaccinated animals. In contrast, no reduction in lesion scores was observed in the animals revaccinated with the TB protein vaccines with their immune responses biased towards induction of antibody.
authors.affiliation: AgResearch, Hopkirk Research Institute, Palmerston North, New Zealand.
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Parlane
authors.affiliation: AgResearch, Hopkirk Research Institute, Palmerston North, New Zealand.
authors.forename: Dairu
authors.initials: D
authors.lastname: Shu
authors.affiliation: AgResearch, Hopkirk Research Institute, Palmerston North, New Zealand.
authors.forename: Supatsak
authors.initials: S
authors.lastname: Subharat
authors.affiliation: AgResearch, Hopkirk Research Institute, Palmerston North, New Zealand.
authors.forename: D Neil
authors.initials: DN
authors.lastname: Wedlock
authors.affiliation: Institute of Fundamental Sciences and MacDiarmid Institute for Advanced Materials and Nanotechnology, Massey University, Palmerston North, New Zealand.
authors.forename: Bernd H A
authors.initials: BH
authors.lastname: Rehm
authors.affiliation: AgResearch, National Centre for Biosecurity and Infectious Disease - Wallaceville, Upper Hutt, New Zealand.
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: de Lisle
authors.affiliation: AgResearch, Hopkirk Research Institute, Palmerston North, New Zealand.
authors.forename: Bryce M
authors.initials: BM
authors.lastname: Buddle
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001500:BCG Vaccine / Q000008:administration & dosage*; D002417:Cattle; D005260:Female; D007117:Immunization, Secondary / Q000662:veterinary*; D007371:Interferon-gamma / Q000097:blood; D008168:Lung / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D009163:Mycobacterium bovis / Q000276:immunology* / Q000472:pathogenicity; D013997:Time Factors; D014374:Tuberculin Test; D032581:Tuberculosis Vaccines / Q000008:administration & dosage; D014380:Tuberculosis, Bovine / Q000175:diagnosis / Q000276:immunology* / Q000517:prevention & control*
chemical_list: D000907:Antibodies, Bacterial; D001500:BCG Vaccine; D032581:Tuberculosis Vaccines; D007371:Interferon-gamma