Ideally, one vaccine candidate would be efficacious in both Regorafenib order animals and humans. While the live strain RB51 protects well in mice and cattle, there

are other ruminant species (i.e. elk, bison, deer) that, depending on the route of vaccination and exposure, and pregnancy status, strain RB51 does not protect against abortion or in some cases disease (Kreeger et al., 2002; Olsen et al., 2003, 2006, 2009; Arenas-Gamboa et al., 2009a, b). Some possible explanations for the lack of protection include differences between the route of vaccination and challenge in their ability to induce protective immunity; the timing of vaccination related to exposure; the immune response of host species (i.e. mechanisms for bias of elk to induce a strong antibody response may limit the cell-mediated immune response); and the ability of lipopolysaccharide of strain 2308 to sequester strain RB51 antigens (Kreeger et al., 2002; Olsen et al., 2003, 2006, 2009; Arenas-Gamboa et

al., 2009a, b). Most recently, Arenas-Gamboa et al. (2009a, b) demonstrated that orally administered encapsulated strain 19 induced protective immunity against a conjunctival challenge with strain 2308 in red see more deer. This suggests that at least some of the limitations in generating protection may be associated with the ability to stimulate protective mucosal immunity. These factors must be weighed in identifying a protective vaccine that could be used for both animals and humans. In conclusion, these studies demonstrated that with the goal of comparing equal doses and duration of treatment: (1) irrespective of viability, B. abortus-attenuated vaccine strain RB51 induced enhanced DC maturation compared with the corresponding pathogenic strain 2308; (2) live strains stimulated greater DC activation and function compared with inactivated strains at the same dose; and (3) neither HK or IR strain RB51 stimulated a strong DC functional response based on cytokine production at tested doses. Potentially

higher doses of or prolonged stimulation with HK or IR strain RB51 could cause BMDCs to produce significant amounts of TNF-α and IL-12 cytokines in vitro and confer protection against challenge OSBPL9 with pathogenic strain 2308 in vivo. Hence, both HK and IR strains could be considered as alternatives to live-attenuated strain RB51. In addition, or as an alternative approach, another method of enhancing the innate response could be to use appropriate TLR agonists to upregulate DC-mediated responses. These studies are warranted as ideally HK or IR vaccine strains with optimal DC and subsequent T-cell function and protection would be optimal for human use (Huang et al., 2003, 2005; Macedo et al., 2008).