The 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

Authors: Waters, Wade; Palmer, Mitchell; STAFNE, MOLLY - Iowa State University; BASS, KRISTIN - Bethyl Laboratories, Inc; MAGGIOLI, MAYARA - Iowa State University; Thacker, Tyler; LINSCOTT, RICK - Idexx Laboratories; LAWRENCE, JOHN - Idexx Laboratories; NELSON, JEFFREY - Animal And Plant Health Inspection Service (APHIS); ESFANDIARI, JAVAN - Chembio Diagnostic Systems, Inc; GREENWALD, RENA - Chembio Diagnostic Systems, Inc; LYASHCHENKO, KONSTANTIN - Chembio Diagnostic Systems, Inc

Submitted to: Clinical and Vaccine Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/3/2015
Publication Date: 4/8/2015
Publication URL: https://handle.nal.usda.gov/10113/60932
Citation: Waters, W.R., Palmer, M.V., Stafne, M.R., Bass, K.E., Maggioli, M., Thacker, T.C., Linscott, R., Lawrence, J.C., Nelson, J.T., Esfandiari, J., Greenwald, R., Lyashchenko, K.P. 2015. The 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. Clinical and Vaccine Immunology. 22(6):641-649.

Interpretive Summary: Despite highly successful eradication efforts in several countries, tuberculosis of cattle remains a serious health concern worldwide. In addition, recent outbreaks of tuberculosis in various states demonstrate that the disease is far from eliminated. Cattle are routinely tested for tuberculosis by tuberculin skin testing as outlined in the United States Department of Agriculture uniform methods and rules for the eradication of bovine tuberculosis in the United States. However, more convenient and specific tests are greatly needed. In the present study, it was determined that cattle experimentally infected with tuberculosis produce antibodies to the bacterium and that these antibodies are detectable by relatively simple laboratory methods. Additionally, antibody responses are significantly boosted, both qualitatively and quantitatively, by the injection of purified protein derivatives for skin test. These methods should prove useful for the development of improved tests for the detection of tuberculous cattle; thereby, providing benefit to the tuberculosis eradication program.

Technical Abstract: Several serologic tests designed to detect antibodies to immunodominant Mycobacterium bovis antigens have recently emerged as ancillary tests for the detection of bovine tuberculosis in cattle, particularly when applied after injection of purified protein derivative (PPD) for skin test that significantly boosts M. bovis-specific antibody responses. Present findings demonstrate the onset and duration of boosted antibody responses after injection of M. bovis PPD for the caudal fold test (CFT) and M. avium and M. bovis PPDs for the comparative cervical test (CCT) applied in series in cattle experimentally-infected with M. bovis. While application of skin tests boosted the response to certain antigens (i.e., MPB83 and MPB70), it did not impact the response to other antigens (e.g., ESAT-6, CFP10, MPB59, and MPB64). Administration of the CCT 105 days after CFT resulted in an even greater secondary boost in antibody responses to MPB83/70 and a proteinase K-digested whole cell sonicate of M. bovis (WCS-PK). Both IgM and IgG contributed to the initial boost in the MPB83/70-specific antibody response after CFT. The secondary boost after CCT was primarily due to increased IgG. Also, the avidity of antibody to MPB83/70 increased after CCT in M. bovis-infected cattle. The avidity of antibody to the WCS-PK antigen increased in the interval between CFT and CCT, but did not increase further after CCT. Together, these findings demonstrate that administration of PPDs for skin test results in additive enhancement (i.e., when the CFT and CCT is applied in series), both qualitative and quantitative, of MPB83/70-specific antibody responses.