Alum adjuvant: some of the tricks of the oldest adjuvant

Abstract

Alum has been the most widely used adjuvant for over 80 years. Although there have been searches for alternative adjuvants, aluminium-containing adjuvants will continue to be used for many years due to their good track record of safety, low cost and adjuvanticity with a variety of antigens. For infections that can be prevented by induction of serum antibodies, aluminium-containing adjuvants formulated under optimal conditions are the adjuvants of choice. There are also some limitations of aluminium-containing adjuvants, which include local reactions, augmentation of IgE antibody responses, ineffectiveness for some antigens and inability to augment cell-mediated immune responses, especially cytotoxic T-cell responses. In this review, we describe the current knowledge regarding the mechanisms (both cellular and molecular) by which alum employs its adjuvant effect, although the final mechanism is not yet well-defined. Furthermore, we discuss how alum's adjuvanticity could be improved.

Innate and adaptive effects of inflammasomes on T cell responses

“…Alum has unanimously been shown to activate the NLRP3 inflammasome in vitro, but the in vivo role of the inflammasome in alum-induced adjuvanticity remains controversial [22][23][24][25][26]. IL-18 and IL-1 preferentially drive Th1/Th17 responses, whereas alum rather polarizes Th2 type immunity, which -by some groups -was found to be unaltered in the absence of caspase-1 or Nlrp3 [24,25].…”

“…IL-18 and IL-1 preferentially drive Th1/Th17 responses, whereas alum rather polarizes Th2 type immunity, which -by some groups -was found to be unaltered in the absence of caspase-1 or Nlrp3 [24,25]. Along this line, whereas IL-1 signaling and inflammasome activity have been implicated in allergic reactions, the importance of the latter in the establishment of such Th2 responses has not been unambiguously delineated [26][27][28]. Therefore, the definitive role of the NLRP3 inflammasome in adjuvanticity might occur through indirect mechanisms, be strongly influenced by the context, and still remains to be clarified.…”

The current challenges for vaccine development

“…This being said, we still do not completely understand the mechanism of action for many of the adjuvants that have been licensed and used for years (Pulendran & Ahmed, 2011;Seubert et al, 2011). Alum has been in use since the 1930s, yet surprisingly its mode of adjuvanticity is only just coming to light (Kool et al, 2012).…”

Novel Strategies in Vaccine Design: Can Nanocapsules Help Prevent and Treat Hepatitis B?

“…Immunization with alum-based hepatitis B vaccines induce a humoral T H 2-directed immune response, which results in the generation of neutralizing antibodies against HBsAg and viral clearance during the acute phase of infection [10]. In contrast, the eradication of chronic HBV infections relies on the induction of robust CD4 + and CD8 + T-cell responses [11,12].…”