title: Efficacy of spheroplastic and cell-wall competent vaccines for Mycobacterium avium subsp. paratuberculosis in experimentally-challenged baby goats.
abstract: A Mycobacterium avium subspecies paratuberculosis (MAP) vaccine that reduced the incidence of clinical disease or reduced fecal shedding of MAP would aid control of Johne's disease (JD). The objective of the present study was to evaluate the efficacy of four MAP vaccine combinations, including cell-wall competent (CWC) alum adjuvant, CWC-QS21 adjuvant, cell-wall deficient (CWD) alum adjuvant and CWD-QS21 adjuvant vaccines. Eighty baby goats were vaccinated at 1 and 4 weeks of age with one of these vaccines or a sham control vaccine consisting of alum adjuvant. Kids were challenged orally with approximately 6.0x10(9) organisms in four divided doses of 1.5x10(9) organisms using a goat isolate of MAP. Vaccinated challenged and challenged control groups had 10 and 6 kids per group, respectively. Half of the kids within each group were necropsied at either 6 or 9 months post-challenge. Gross and microscopic lesions and relative number of acid-fast bacilli were evaluated and scored at necropsy. Results indicated all challenged kids had some lesions compatible with JD suggesting none of the vaccines prevented infection. Three vaccines (CWC-alum, CWC-QS21 and CWD-QS21) reduced lesion scores by 46-51% at 9 months. CWD-alum vaccine resulted in a more severe (+33.5%) lesion score than sham-vaccinated challenged control. Lesion scores were greater at 9 months than at 6 months post-challenge in the sham-vaccinated challenged group and CWD-alum vaccinated group, while lesion scores were generally stable with remaining vaccines. Mean fecal CFU/g were significantly different across time from challenge to 9-month necropsy (p=0.043) and the CWC-QS21 vaccine group had a marked reduction in fecal CFU/g at all time points post-challenge. A reduction in MAP CFU/g was also detected in necropsy tissues from kids given the CWC-alum, CWC-QS21 and CWD-QS21 vaccines, and increased CFU/g were detected in tissues from kids given the CWD-alum vaccine. Immunological tests evaluated included, humoral response evaluation by AGID, ELISA and Western blot, and cell mediated response by comparative PPD skin testing (M. avium, Old Johnin, M. bovis and Lot 2 Johnin PPD's), and production of MAP induced gamma-interferon. Vaccination also resulted in false-positive PPD skin test reactions for M. avium PPD, Old Johnin PPD and gamma-interferon tests. When a 2-mm cutoff above normal skin thickness was used to define positive skin test reactions, false-positive reactions for M. bovis were detected in only 2 of 32 kids given a vaccine with QS21 adjuvant.
authors.affiliation: University of Georgia, Tifton Veterinary Diagnostic and Investigational Laboratory, Tifton, GA 31793, USA. mhinesii@uga.edu
authors.forename: Murray E
authors.initials: ME
authors.lastname: Hines
authors.forename: Shane
authors.initials: S
authors.lastname: Stiver
authors.forename: Dipak
authors.initials: D
authors.lastname: Giri
authors.forename: Lisa
authors.initials: L
authors.lastname: Whittington
authors.forename: Cindy
authors.initials: C
authors.lastname: Watson
authors.forename: Jill
authors.initials: J
authors.lastname: Johnson
authors.forename: Julie
authors.initials: J
authors.lastname: Musgrove
authors.forename: Mel
authors.initials: M
authors.lastname: Pence
authors.forename: David
authors.initials: D
authors.lastname: Hurley
authors.forename: Charles
authors.initials: C
authors.lastname: Baldwin
authors.forename: Ian A
authors.initials: IA
authors.lastname: Gardner
authors.forename: Sharif
authors.initials: S
authors.lastname: Aly
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001428:Bacterial Vaccines / Q000592:standards*; D001772:Blood Cell Count / Q000662:veterinary; D001831:Body Temperature; D002473:Cell Wall / Q000276:immunology; D015169:Colony Count, Microbial / Q000662:veterinary; D005243:Feces / Q000382:microbiology; D015511:Goat Diseases / Q000382:microbiology / Q000503:physiopathology / Q000517:prevention & control*; D006041:Goats; D007422:Intestines / Q000382:microbiology / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D016927:Mycobacterium avium subsp. paratuberculosis / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D010283:Paratuberculosis / Q000382:microbiology / Q000503:physiopathology / Q000517:prevention & control*; D012680:Sensitivity and Specificity; D013104:Spheroplasts / Q000276:immunology; D013997:Time Factors; D014611:Vaccination / Q000662:veterinary
chemical_list: D001428:Bacterial Vaccines