β-Glucan as Trained Immunity-Based Adjuvants for Rabies Vaccines in Dogs

Abstract

The mechanisms of trained immunity have been extensively described in vitro and the beneficial effects are starting to be deciphered in in vivo settings. Prototypical compounds inducing trained immunity, such as β-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 β-glucans as well as their capacity to enhance the adaptive immune response of an inactivated rabies vaccine (Rabisin ® ). Injection of β-glucan from Euglena gracilis was performed 1 month before vaccination with Rabisin ® supplemented or not with the same β-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 β-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 β-glucan or not. Our preliminary results support that adjuvantation of Rabisin ® vaccine with β-glucan elicit a higher B-lymphocyte immune response, the prevailing factor of protection against rabies. β-glucan also tend to stimulate the T cell response as shown by the cytokine secretion profile of PBMCs re-stimulated ex 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 β-glucan, 1 month before or simultaneously to Rabisin ® vaccination give promising results for the generation of new TIbA candidates and their potential to provide increased immunogenicity of specific vaccines.

Do bacterial vaccines/adjuvants prevent wheezing episodes in children?

“…Such an enhancement may also be relevant when considering adaptive responses to natural infections. This has been demonstrated in experimental models of immunization with bystander antigens with MV130 [36 && ,47] or with others inducers of trained immunity [57], raising the concept of trained immunity-based adjuvants [27]. In fact, the well known complete Freund's adjuvant does contain heat-killed Mycobacterium tuberculosis [58].…”

Trained immunity: A “new” weapon in the fight against infectious diseases

“…Since Netea’s study, β-glucans, especially in the context of C. albicans infection, have been extensively explored in trained immunity. The potential of β-glucans as a vaccine adjuvant for infectious diseases lacking an effective vaccine—such as leishmaniasis, tuberculosis, and rabies—is a particularly hot topic ( 27 , 87 , 88 ). Though less at the forefront, work has also been conducted in dietary β-glucans— derived from oats rather than the fungal cell wall.…”

Beta 1,3-1,6 Glucans Produced by Two Novel Strains of Aureobasidium Pullulans Exert Immune and Metabolic Beneficial Effects in Healthy Middle-aged Japanese Men: Results of an Exploratory Randomized Control Study

“…The potential of the AFO-202 and N-163 beta glucan as an immune adjuvant in the prophylaxis of COVID-19, along with beneficial anti-coagulopathy benefits in clinical trials, has been described (16)(17)(18)(19)(20). These beta glucans have also been effective as inti-infective agents against viral infections such as dengue, influenza, rabies apart from beneficial immune-modulation in sepsis (21)(22)(23)(24).…”