Novel adjuvants for B cell immune responses

To summarize recent progress in the development of adjuvants with a special focus on adjuvants that enhance B-cell responses to protein-based vaccines. Both established and new experimental approaches are described and also briefly we discuss how adjuvants and virus-based vaccines interact with the immune system.

Two new adjuvants were recently approved for human applications and many others are in preclinical or clinical testing. Significant advances were made to describe the mechanism of action of adjuvants. For example, aluminum hydroxide salts were shown to engage Nalp3, a member of the cytosolic NOD-like receptors and activation of B cells via invariant natural killer cell presentation of alpha-galactosylceramide was described. The effects of Toll-like receptor ligands on B-cell differentiation were further characterized and a peptide derived from IPS-1, a cytosolic signaling molecule, was shown to provide adjuvant effect. Stimulation of protective antibodies against HIV-1 may require extensive antibody affinity maturation, thus long-term exposure or repeated administration of antigen may be needed to induce effective B-cell responses.

Advances in our understanding of how specific signaling pathways link innate and adaptive immunity provides a basis for the design of improved adjuvants to promote broad and potent B-cell responses.