Inulin‐derived adjuvants efficiently promote both Th1 and Th2 immune responses

Abstract

Summary There has been a recent resurgence of interest into new and improved vaccine adjuvants. This interest has been stimulated by the need for new vaccines to combat problematic pathogens such as SARS and HIV, and to counter potential bioterrorist attacks. A major bottleneck in vaccine development is the low immunogenicity of purified subunit or recombinant proteins, creating the need for safe human adjuvants with high potency. A major problem in the search for the ideal adjuvant is that adjuvants that promote cell-mediated (Th1) immunity (e.g. Freund's complete adjuvant) generally have unacceptable local or systemic toxicity that precludes their use in human vaccines. There is a need for a safe, non-toxic adjuvant that is able to stimulate both cell-mediated and humoral immunity. Inulin-derived adjuvants that principally stimulate the innate immune system through their ability to activate the alternative complement pathway have proven ability to induce both cellular and humoral immunity. With their excellent tolerability, long shelf-life, low cost and easy manufacture, they offer great potential for use in a broad range of prophylactic and therapeutic vaccines. Based on successful animal studies in a broad range of species, human trials are about to get underway to validate the use of inulin-based adjuvants in prophylactic vaccines against hepatitis B, malaria and other pathogens. If such trials are successful, then it is possible that inulinderived adjuvants will one day replace alum as the adjuvant of choice in most human prophylactic vaccines.

TLR-Induced Local Metabolism of Vitamin D3 Plays an Important Role in the Diversification of Adaptive Immune Responses

“…It has long been appreciated that the inclusion of aluminum hydroxide (Alum) into vaccines is capable of enhancing elicited humoral immune responses in a Th2 cell-biased manner (1), whereas an inclusion of highly inflammatory CFA effectively stimulates humoral and cellular immune responses through mechanisms largely regulated by Th1 cells (2).…”

Potentiation of photodynamic therapy of cancer by complement: the effect of γ-inulin

“…Treatment of mice with g-inulin was shown to result in deposition of complement C3-fragments on the surface of macrophages, which enables these antigen-presenting cells (APCs) to greatly increase their efficacy in enhancing the proliferation of antigen-specific T cells (Kerekes et al, 2001). Gamma-inulin is also a powerful adjuvant of the antibody responses (Cooper and Steele, 1988;Silva et al, 2004). Owing to these properties, there is also interest in g-inulin as vaccine adjuvant, its safety for human use has been verified (Frazer et al, 1999).…”

Complement-mediated ‘bystander’ damage initiates host NLRP3 inflammasome activation

“…Several groups have proposed that complement can be a natural adjuvant to promote immune responses (Bánki et al, 2010;Dempsey et al, 1996;Haas et al, 2004;Stäger et al, 2003), and that complement activation by adjuvants can enhance vaccine efficacy (Kerekes et al, 2001). Complement activation is thought to play an important role in the adjuvant effects of alum (Güven et al, 2013), and novel adjuvants based on inulin have been shown to be potent inducers of the T H 1 and T H 2 immune response (Silva et al, 2004). Complement-opsonized antigens, like HIV (Bánki et al, 2010; Haas et al, 2004) and anthrax (Kolla et al, 2007), are better at activating T cells than their unopsonized counterparts.…”