Immunity and vaccine failure

To understand why some sheep fail to respond adequately to vaccination against footrot, we studied the systemic adaptive and innate immune responses; we found that they were unlikely to be responsible for therapeutic vaccination non-response.

Bhardwaj, V., Dhungyel, O., De Silva, K. and Whittington, R. J. (2014) Investigation of immunity in sheep following footrot infection and vaccination. Vaccine, 32, 6979-6985. 10.1016/j.vaccine.2014.10.031

Summary: Ovine footrot is a major disease affecting sheep welfare and production. The anaerobic Gram-negative bacterium Dichelobacter nodosus is the essential transmitting agent. Monovalent or bivalent vaccines induce high levels of D. nodosus antibodies and are the basis of several successful footrot treatment, control and eradication programs. Due to the rapid rate of disease transmission within a flock, the presence of therapeutic vaccination non-responders has major implications for a control program. The aim of this study was to assess the immunological basis of a therapeutic vaccination non-response. Sheep (n = 120) were infected with D. nodosus in an artificial pen challenge. Once disease had established, animals were vaccinated with a serogroup specific D. nodosus fimbrial vaccine. Based on the response to therapeutic vaccination, animals were allocated into one of three groups: (i) TVNR where disease persisted despite vaccination (ii) non-diseased, where disease never established and (iii) TVR, where disease was established but resolved with vaccination. Factors related to both the innate and adaptive immune pathways were assessed. These included antigen-specific serum antibodies, interferon-gamma, interleukin-10, proliferation of lymphocyte subsets and phagocytic activity of leukocytes. There was no significant difference between the three groups of sheep for any of these parameters. All three groups of sheep produced antibody in excess of a previously published minimum antibody titre required for protection. Opsonising activity in sera from the three groups of sheep was also not significantly different and phagocytic cells from sheep from all three groups were able to destroy D. nodosus intracellularly. These findings show that the measured systemic adaptive and innate immune responses were unlikely to be the cause of a therapeutic vaccination non-response. They also show that the accepted minimum protective titre may be incorrect and may need further examination.

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