<p class="first" id="d5876450e83">After decades of slow progress, the last years have
seen a rapid acceleration of the
development of adjuvanted vaccines which have lately been approved for human use.
These adjuvants consist of different components, e.g. aluminium salts, emulsions such
as MF59 and AS03, Toll-like receptor (TLR) agonists (CpG ormonophosphoryl lipid A
(MPL) adsorbed on aluminium salts as in AS04) or combination of immunopotentiators
(QS-21 and MPL in AS01). Despite their distinctive features, most of these adjuvants
share some key characteristics. For example, they induce early activation (although
at different levels) of innate immunity which then translates into higher antibody
and cellular responses to the vaccine antigens. In addition, most of these adjuvants
(e.g. MF59, AS03, AS04) clearly induce a wider breadth of adaptive responses able
to confer protection against, for example, heterovariants of the influenza viruses
(MF59, AS03) or against human papillomavirus strains not contained in the vaccine
(AS04). Finally, the use of some of these adjuvants has contributed to significantly
enhance the immune response and the efficacy and effectiveness of vaccines in the
elderly who experience a waning of the immune responsiveness to infection and vaccination,
as shown for MF59- or AS03-adjuvanted influenza vaccines and AS01-adjuvanted herpes
zoster vaccine. These results, together with the track record of acceptable safety
profiles of the adjuvanted vaccines, pave the way for the development of novel vaccines
at the extremes of age and against infections with a high toll of morbidity and mortality.
Here, we review the mechanisms associated with the performance of those adjuvanted
vaccines in animal models and in humans through recent advances in systems vaccinology
and biomarker discovery. We also provide some perspectives on remaining knowledge
gaps but also on opportunities that could accelerate the development of new vaccines.
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