Effects of Serial Skin Testing with Purified Protein Derivative on the Level and Quality of Antibodies to Complex and Defined Antigens in Mycobacterium bovis-Infected Cattle

Abstract

Bovine tuberculosis of cattle results primarily from infection with Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex. Despite intensive control efforts, bovine tuberculosis persists as a costly disease, with adverse impacts on animal health and welfare, the trade of animals and animal products, and the livelihoods of producers. In addition, the persistence of this disease necessitates the maintenance of costly regional and federal networks for control/eradication campaigns. The mainstays of bovine tuberculosis control are (i) abattoir surveillance with epidemiological investigations after detection of M. bovisinfected animals, to identify bovine tuberculosis-affected herds (1); (ii) application of antemortem testing for routine surveillance, movement of animals, and identification and removal of infected animals from tuberculosis-affected herds (2); and (iii) management of the disease in wildlife reservoirs, such as whitetailed deer in Michigan (3), brushtail possums (Trichosurus vulpecula) in New Zealand, Eurasian wild boar (Sus scrofa) and red deer (Cervus elaphus) in Spain (4), and Eurasian badgers (Meles meles) in the United Kingdom/Ireland (5). Tuberculin-based cellular immune assays, including measurements of in vitro interferon gamma release and measurements of delayed-type hypersensitivity (DTH) reactions via skin test procedures, are the principal diagnostic tests used for the control of bovine tuberculosis in cattle in most countries (6, 7). In the United States, the caudal fold test (CFT) (intradermal injection of M. bovis purified protein derivative [PPD] in the caudal skin fold) is used as a primary test and the comparative cervical test (CCT) (intradermal injection of Mycobacterium avium and M. bovis PPDs at separate sites in the neck) and the Bovigam assay (Prionics Ag, Schlieren, Switzerland) (an interferon gamma release assay) are used as secondary or confirmatory tests (8).Several serological tests designed to detect antibodies (Abs) to immunodominant M. bovis antigens (e.g., MPB83, MPB70, ESAT-6, and CFP10) have emerged for potential application in cattle (9-13). A commercial enzyme-linked immunosorbent assay (ELISA) for MPB83 and MPB70 (M. bovis Ab test; IDEXX Laboratories, Westbrook, ME) (9) has been approved by the Office International des Epizooties and the U.S. Department of Agriculture (USDA) for use in cattle in bovine tuberculosis control programs, although applications of this test are primarily limited to ancillary purposes such as confirmation of infections and potentially detection of M. bovis-infected cattle anergic in the skin test. A

Serological Analysis of Tuberculosis in Goats by Use of the Enferplex Caprine TB Multiplex Test

“…Many studies have reported an anamnestic antibody response following skin testing in cattle and other species, including goats (2,27,(30)(31)(32)(33)(34)(35). Our data show that in 122 animals that received SIT in May 2014, the proportions that were anti-PPD-B antibody positive and the absolute levels of anti-PPD-B antibody 31 days after PPD-B injection were significantly higher than those observed 3 days after PPD-B injection, suggesting that some boosting had taken place 31 days following PPD-B administration.…”

Identification of Novel Antigens Recognized by Serum Antibodies in Bovine Tuberculosis

“…Our previous research on bovine TB serology using enzyme-linked immunosorbent assay (ELISA), Western blotting, and MAPIA has demonstrated that (i) antibody responses to M. bovis involve multiple antigens, including MPB64, MPB70, MPB83, CFP10, and ESAT-6, with remarkable animal-to-animal variations in reactivity patterns (20); (ii) IgM and IgG antibodies can be detected in blood 3 to 4 and 4 to 6 weeks, respectively, after M. bovis inoculation (2, 17); (iii) individual seroreactivity profiles may evolve with disease progression (20); (iv) the variability and evolution of the humoral immune response may be addressed by use of multiantigen cocktails to maximize the diagnostic sensitivity of serological assays (17,20,25); (v) antibody responses in M. bovis-infected cattle are boosted following PPD injection for skin testing (3,25); and (vi) at advanced disease stages, antibody levels positively correlate with lesion severity (25,26).…”

“…Serum samples were obtained from Holstein steers that had been aerosol infected with M. bovis (ϳ10 4 CFU of strain 95-1315 or 10-7428) in four experiments performed as described previously (2,3,31) in a biosafety level 3 (BSL-3) facility at the National Animal Disease Center, Ames, IA, in accordance with Institutional Biosafety and Animal Care and Use Committee guidelines. Serial samples were collected at multiple time points postinoculation.…”

“…Although M. bovis is most often isolated from tuberculous cattle, it has a broad range of susceptible host species, including humans (2)(3)(4). The control of TB in cattle is therefore difficult due to the existence of wildlife reservoirs of M. bovis, such as white-tailed deer in the United States, Eurasian badgers in Great Britain, wild boars in Spain, and brushtail possums in New Zealand (5)(6)(7)(8).…”

Proteomic analysis of protein purified derivative of Mycobacterium bovis

“…Those animals that react to PPD are isolated and slaughtered [11, 12]. Despite intensive eradication efforts over decades, bTB persists as a costly disease with adverse impacts on animal health and welfare, trade of animals and animal products, and livelihoods of producers, and continues to be a problem with global perspectives [4, 13]. It has been suggested that TST is a good herd test but a poor test for identifying individual infected animals [4].…”