The vaccine adjuvant alum promotes IL‐10 production that suppresses Th1 responses

Abstract

The effectiveness of many vaccines licensed for clinical use relates to the induction of neutralising antibodies, facilitated by the inclusion of vaccine adjuvants, particularly alum. However, the ability of alum to preferentially promote humoral rather than cellular, particularly Th1-type responses, is not well understood. We demonstrate that alum activates immunosuppressive mechanisms following vaccination, which limit its capacity to induce Th1 responses. One of the key cytokines limiting excessive immune responses is IL-10. Injection of alum primed draining lymph node cells for enhanced IL-10 secretion ex vivo. Moreover, at the site of injection, macrophages and dendritic cells were key sources of IL-10 expression. Alum strongly enhanced the transcription and secretion of IL-10 by macrophages and dendritic cells. The absence of IL-10 signalling did not compromise alum-induced cell infiltration into the site of injection, but resulted in enhanced antigen-specific Th1 responses after vaccination. In contrast to its decisive regulatory role in regulating Th1 responses, there was no significant change in antigen-specific IgG1 antibody production following vaccination with alum in IL-10-deficient mice. Overall, these findings indicate that injection of alum promotes IL-10, which can block Th1 responses and may explain the poor efficacy of alum as an adjuvant for inducing protective Th1 immunity.

<p>Crystalline and Amorphous Preparation of Aluminum Hydroxide Nanoparticles Enhances Protective Antigen Domain 4 Specific Immunogenicity and Provides Protection Against Anthrax</p>

“…Additionally, it has been demonstrated recently that alum adjuvant activates immunosuppressive mechanisms following vaccination with the help of increased production of IL-10 cytokine by macrophages and DCs, which limits its ability to induce Th1-type immune responses. 31 As observed in this study, the level of IL-10 cytokine in both AH nps immunized mice groups was statistically low as compared to the commercial adjuvant AH gel group (P< 0.001). Taken together with the results of enhanced productions of Th1-type cytokines, the decreased production of IL-10 cytokine indicates that the induction of Th1-type immune response in the crystalline and amorphous AH nps mice groups were not restrained.…”

IL-33 Is a Negative Regulator of Vaccine-Induced Antigen-Specific Cellular Immunity

“…Alum can induce modest Ag-specific CD8 + responses in mice following vaccination by i.p. (17) or i.m. routes (18).…”

Advances of functional nanomaterials for cancer immunotherapeutic applications

“…Alumina NPs have a self-adjuvant effect, and some studies have focused on their mechanism of action, for example, activation of the NACHT, LRR and PYD domains-containing protein 3 (NALP3) inflammasome in DCs (Eisenbarth, Colegio, O'Connor, Sutterwala, & Flavell, 2008;Kool et al, 2008). Ewa Oleszycka et al found that alum-mediated adjuvant works by suppressing Th1 responses and the key cytokines IL-10 which suppressed Th1 responses promoted by priming DLN cells after injection of alum (Oleszycka et al, 2018). Haiyan et al reported a nanovaccine composed of α-Al 2 O 3 as antigens carrier.…”