Evaluation of granulysin and perforin as candidate biomarkers for protection following vaccination with Mycobacterium bovis BCG or M. bovis DeltaRD1

The development of improved vaccines against tuberculosis (TB) is directly linked to the investigation of new and better correlates of protection after vaccination against TB. Cloning and characterization of bovine homologues of the antimicrobial protein granulysin (Bo-lysin) and perforin by our group could be used as potential biomarkers for TB vaccination efficacy. In the present study we examined the kinetics of granulysin, perforin, IFNgamma and Fas-L responses to Mycobacterium bovis purified protein derivative (PPD) stimulation by peripheral blood mononuclear cells from M. bovis DeltaRD1-, BCG- and non-vaccinated cattle. Gene expression profiles following PPD stimulation showed significant increases in transcripts for granulysin and IFNgamma in both CD4+ and CD8+ T cells in BCG-vaccinated as compared to non-vaccinated animals. Perforin and IFNgamma examined by flow cytometry, showed a difference of 1-2% more PPD-specific cells in BCG-vaccinated than non-vaccinated animals. In the vaccine trial, granulysin and perforin were significantly increased in both vaccine groups as compared to control after vaccination and challenge. IFNgamma expression was increased only after vaccination and secretion was higher in the control, as compared to both vaccine groups demonstrating no correlation with protection upon vaccination. In summary, results shown here provide evidence that granulysin and perforin are prospective candidates as biomarkers of protection after vaccination against TB.

Name thesis:degree_name

PhD

Level thesis:degree_level

Doctoral

Grantor

The University of Texas Medical Branch

Year dc:date.issued

2008

Author dc:creator

• Charles Fernando Capinos Scherer

Advisor dc:contributor.advisor

• D. Mark Estes

Committee members dc:contributor.committeemember

• Slobodan Paessler
• Janice J. Endsley
• Gregg N. Milligan
• Bernardo Villarreal-Ramos
• Alfredo G. Torres

• vaccination
• perforin
• Mycobacterium bovis
• granulysin
• biomarkers

Statement dc:rights

• Copyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works.

Language dc:language.iso

eng

Dc Identifier Other

etd-12312008-061540

OAI identifier oai:identifier

oai:utmb-ir.tdl.org:2152.3/300