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Title:   Author  item
                                            Waters, Wadeitem
                                            Palmer, Mitchellitem
                                            Olsen, Stevenitem
                                            Sacco, Randyitem
                                            Whipple, Diana
  Submitted to: Vaccine
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 10/9/2002
                                    Publication  Date: 3/28/2003
                                    Citation: Waters, W.R., Palmer, M.V., Olsen, S.C., Sacco, R.E., Whipple, D.L. 2003. Immune responses of elk to mycobacterium bovis bacillus calmette guerin vaccination. Vaccine.  Vol. 21(13-14), p. 1518-1526.Interpretive Summary: Recently, there has been an increased interest in the role of elk in disease transmission to domestic livestock.  Most notably, elk are considered reservoirs for brucellosis, Johne's disease, and tuberculosis, each serious pathogens of domestic livestock.  Information concerning basic immune responsiveness of elk, however, is lacking.  In the present study, it was determined that the immune response of elk to a live tuberculosis vaccine differs from that of cattle.  Most notably, the subset of immune cells responding to the vaccine of elk differed from that of cattle.  These findings will aid future development of improved diagnostic tests of tuberculosis and, potentially, other diseases of elk.
                                Technical Abstract: Detection of Mycobacterium bovis infection of captive or free-ranging elk (Cervus elaphus), although rare, elicits serious concern due to regulatory and zoonotic implications.  As captive cervids are frequently moved between herds and often across state and national borders, the development of improved diagnostic capabilities and vaccines for tuberculosis would be particularly desirable for this growing industry.  To model natural infection, elk were vaccinated with live Mycobacterium bovis bacillus Calmette Guerin (BCG, Pasteur strain) for evaluation of immune responsiveness to this attenuated live vaccine.  Peripheral blood mononuclear cells (PBMC) of vaccinated elk proliferated in response to stimulation with a soluble mycobacterial antigen preparation (i.e., M. bovis purified protein derivative, PPDb).  Greater numbers of sIgM+ cells (i.e., B cells) proliferated in this response than did either CD4+, gammadelta TCR+ or CD8+ cells.  The in vivo response (i.e., delayed type hypersensitivity) to PPDb by vaccinated elk exceeded both the response by non-vaccinated elk and BCG-vaccinated cattle at 24-, 48-, and 72-h post administration of PPD.  In vivo responses to PPDb by vaccinated elk diminished after 72 h as compared to responses at 24 and 48 h.  Serum was also collected periodically and evaluated by ELISA for immunoglobulin (i.e., IgG heavy and light chains) reactivity to crude mycobacterial antigens.  Two weeks post vaccination and throughout the duration of the study, serum immunoglobulin reactivity to PPDb and to a proteinase K-digested whole cell sonicate of BCG exceeded that of serum from non-vaccinated elk.  Intradermal administration of PPD for measurement of hypersensitive responses boosted the serum antibody response.  These findings demonstrate that BCG vaccination of elk induces a serum antibody response to crude M. bovis antigens, a B cell in vitro proliferative response, and in vivo trafficking of mononuclear cells to sites of mycobacterial antigen administration (i.e., delayed type hypersensitivity).  A predominant B cell in vitro proliferative response by elk PBMC to crude mycobacterial test antigens will likely impact the development of improved diagnostic tests of tuberculosis infection for this species.


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