New-age adjuvants: friend or foe?

Older vaccines made from live or killed whole organisms were effective, but suffered from high reactogenicity. As vaccine manufacturers developed safer, less reactogenic subunit vaccines, they found that with lower reactogenicity came reduced vaccine effectiveness. Somewhat ironically, the solution proposed to boost immunogenicity in modern vaccines is to add back immune-activating substances such as toll-like receptor agonists - the very same contaminants removed from old-style vaccines. This raises the question of whether the vaccine field is moving forward or backward. We propose that by avoiding adjuvants that work through toll-like receptor (TLR) pathways, and instead focusing on adjuvants stimulating B-and T-cell immunity directly, one can minimize inflammatory cytokine production and consequent reactogenicity. We present data on a polysaccharide-based adjuvant candidate, Advax, that enhances immunogenicity without reactogenicity, suggesting that potent and well-tolerated vaccines for both adult and pediatric use are indeed possible.