Β-Glucan As Trained Immunity-Based Adjuvants for Rabies Vaccines in Dogs.

The mechanisms of trained immunity have been extensively describedin vitroand the beneficial effects are starting to be deciphered inin vivosettings. Prototypical compounds inducing trained immunity, such as beta-glucans, act through epigenetic reprogramming and metabolic changes of innate immune cells. The recent advances in this field have opened new areas for the development of Trained immunity-based adjuvants (TIbAs). In this study, we assessed in dogs the potential immune training effects of beta-glucans as well as their capacity to enhance the adaptive immune response of an inactivated rabies vaccine (Rabisin(R)). Injection of beta-glucan fromEuglena graciliswas performed 1 month before vaccination with Rabisin(R)supplemented or not with the same beta-glucan used as adjuvant. Trained innate immunity parameters were assessed during the first month of the trial. The second phase of the study was focused on the ability of beta-glucan to enhance adaptive immune responses measured by multiple immunological parameters. B and T-cell specific responses were monitored to evaluate the immunogenicity of the rabies vaccine adjuvanted with beta-glucan or not. Our preliminary results support that adjuvantation of Rabisin(R)vaccine with beta-glucan elicit a higher B-lymphocyte immune response, the prevailing factor of protection against rabies. beta-glucan also tend to stimulate the T cell response as shown by the cytokine secretion profile of PBMCs re-stimulatedex vivo.Our data are providing new insights on the impact of trained immunity on the adaptive immune response to vaccines in dogs. The administration of beta-glucan, 1 month before or simultaneously to Rabisin(R)vaccination give promising results for the generation of new TIbA candidates and their potential to provide increased immunogenicity of specific vaccines.