Israeli, E; Agmon-Levin, N; Blank, M; Shoenfeld, Y
Some adjuvants may exert adverse effects upon injection or,
on the other hand, may not trigger a full immunological reaction. The mechanisms underlying
adjuvant adverse effects are under renewed scrutiny because of the enormous implications for
vaccine development. In the search for new and safer adjuvants, several new adjuvants were
developed by pharmaceutical companies utilizing new immunological and chemical innovations. The
ability of the immune system to recognize molecules that are broadly shared by pathogens is, in
part, due to the presence of special immune receptors called toll-like receptors (TLRs) that are
expressed on leukocyte membranes. The very fact that TLR activation leads to adaptive immune
responses to foreign entities explains why so many adjuvants used today in vaccinations are
developed to mimic TLR ligands. Alongside their supportive role, adjuvants were found to inflict
by themselves an illness of autoimmune nature, defined as 'the adjuvant diseases'. The
debatable question of silicone as an adjuvant and connective tissue diseases, as well as the Gulf
War syndrome and macrophagic myofaciitis which followed multiple injections of aluminium-based
vaccines, are presented here. Owing to the adverse effects exerted by adjuvants, there is no
doubt that safer adjuvants need to be developed and incorporated into future vaccines. Other
needs in light of new vaccine technologies are adjuvants suitable for use with mucosally
delivered vaccines, DNA vaccines, cancer and autoimmunity vaccines. In particular, there is
demand for safe and non-toxic adjuvants able to stimulate cellular (Th1) immunity. More adjuvants
were approved to date besides alum for human vaccines, including MF59 in some viral vaccines,
MPL, AS04, AS01B and AS02A against viral and parasitic infections, virosomes for HBV, HPV and
HAV, and cholera toxin for cholera. Perhaps future adjuvants occupying other putative receptors
will be employed to bypass the TLR signaling pathway completely in order to circumvent common
side effects of adjuvant-activated TLRs such as local inflammation and the general malaise felt
because of the costly whole-body immune response to antigen. Lupus (2009) 18, 1217-1225.