Research on a TB vaccine for use in free-ranging white-tailed deer

Authors: Palmer, Mitchell; Kanipe, Carly; Boggiatto, Paola

Submitted to: United States Animal Health Association Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 10/5/2021
Publication Date: N/A
Citation: N/A

Interpretive Summary: In 1995 a focus of Mycobacterium bovis infection among free-ranging white-tailed deer was identified in northeast Michigan. It is believed that deer originally acquired M. bovis as it spilled over from cattle-to-deer. Initial efforts to decrease deer population densities through increased hunting and elimination of supplemental feeding successfully decreased disease prevalence among deer. Increased cattle testing identified multiple infected herds, which were removed. It is believed that cattle were infected as M. bovis spilled back from deer-to-cattle. In spite of these efforts, disease prevalence among deer has remained steady at approximately 2% for over a decade, and 2-3 infected cattle herds are identified each year in northeast Michigan. It is evident that additional tools are needed. Vaccination of deer would be an additional tool to decrease deer-to-deer and deer-to-cattle transmission of M. bovis. The human vaccine, M. bovis strain BCG has been demonstrated to reduce disease severity in deer whether administered by SC injection or by oral delivery of liquid vaccine. Lyophilization is often used to increase vaccine stability, facilitate handling or transport, and allow for encapsulation within gelatin capsules. BCG was lyophilized and pre- and post-lyophilization quantitative culture demonstrated a minimal effect on viability. Lyophilized BCG was encapsulated and placed within a feedstuff previously shown to be palatable to free-ranging deer. The feedstuff was termed a vaccine delivery unit (VDU). Captive, hand-raised deer were acclimated to blank VDUs before offering VDUs containing BCG. VDUs containing BCG were offered to deer, which were voluntarily consumed. Deer were observed to ensure complete ingestion of a single VDU. Immune responses were monitored using in vitro proliferation assays of M. bovis PPD (PPDb) stimulated peripheral blood mononuclear cells (PBMC), as well as tuberculin skin testing (TST). Proliferative responses to PPDb stimulation were minimal to absent at 4, 8, 12 and 16 weeks after vaccination. Similarly, there were few conversions from pre-vaccination negative TST responses to positive TST reactions 16 weeks after vaccination. In contrast to instillation of liquid vaccine, which immediately exposes key oropharyngeal lymphoid tissues such as tonsils, use of a VDU containing encapsulated, lyophilized BCG requires that the capsule be broken through chewing, lyophilized BCG, mixed with feedstuff, be reconstituted using available saliva, and that reconstituted BCG reach important oropharyngeal lymphoid tissues. As such, limited exposure of oropharyngeal lymphoid tissues to active, reconstituted BCG is believed to be the cause of lack of responsiveness in the current study. Alternative methods to deliver liquid BCG, which has been shown to be effective, should be explored.

Technical Abstract: In 1995 a focus of Mycobacterium bovis infection among free-ranging white-tailed deer was identified in northeast Michigan. It is believed that deer originally acquired M. bovis as it spilled over from cattle-to-deer. Initial efforts to decrease deer population densities through increased hunting and elimination of supplemental feeding successfully decreased disease prevalence among deer. Increased cattle testing identified multiple infected herds, which were removed. It is believed that cattle were infected as M. bovis spilled back from deer-to-cattle. In spite of these efforts, disease prevalence among deer has remained steady at approximately 2 percent for over a decade, and 2-3 infected cattle herds are identified each year in northeast Michigan. It is evident that additional tools are needed. Vaccination of deer would be an additional tool to decrease deer-to-deer and deer-to-cattle transmission of M. bovis. The human vaccine, M. bovis strain BCG has been demonstrated to reduce disease severity in deer whether administered by SC injection or by oral delivery of liquid vaccine. Lyophilization is often used to increase vaccine stability, facilitate handling or transport, and allow for encapsulation within gelatin capsules. BCG was lyophilized and pre- and post-lyophilization quantitative culture demonstrated a minimal effect on viability. Lyophilized BCG was encapsulated and placed within a feedstuff previously shown to be palatable to free-ranging deer. The feedstuff was termed a vaccine delivery unit (VDU). Captive, hand-raised deer were acclimated to blank VDUs before offering VDUs containing BCG. VDUs containing BCG were offered to deer, which were voluntarily consumed. Deer were observed to ensure complete ingestion of a single VDU. Immune responses were monitored using in vitro proliferation assays of M. bovis PPD (PPDb) stimulated peripheral blood mononuclear cells (PBMC), as well as tuberculin skin testing (TST). Proliferative responses to PPDb stimulation were minimal to absent at 4, 8, 12 and 16 weeks after vaccination. Similarly, there were few conversions from pre-vaccination negative TST responses to positive TST reactions 16 weeks after vaccination. In contrast to instillation of liquid vaccine, which immediately exposes key oropharyngeal lymphoid tissues such as tonsils, use of a VDU containing encapsulated, lyophilized BCG requires that the capsule be broken through chewing, lyophilized BCG, mixed with feedstuff, be reconstituted using available saliva, and that reconstituted BCG reach important oropharyngeal lymphoid tissues. As such, limited exposure of oropharyngeal lymphoid tissues to active, reconstituted BCG is believed to be the cause of lack of responsiveness in the current study. Alternative methods to deliver liquid BCG, which has been shown to be effective, should be explored.