Synthetic adjuvants for vaccine formulations: phytol derivatives

The development of vaccines is considered a key milestone in preventive medicine. There is no comparable cost-effective means for controlling or eradicating infectious diseases. Yet, a persistent societal problem is the concern about vaccine's safety and long-term effects, and this caters to detractors of vaccination. Pathogen-derived antigen(s) as well as adjuvants/immunostimulants are essential for vaccine efficacy. Currently, adjuvant selection is largely empirical, but the mechanism underlying adjuvanticity is beginning to unravel. This should help develop more defined or targeted adjuvants.

This review provides a brief account and analysis of the host immune parameters modulated by some commonly used as well as new adjuvants, including phytol-based diterpenoids. The major efforts are directed toward evaluating their relative safety and immunomodulatory efficiency, compared to known synthetic and natural adjuvants. Concerns for adverse pathological inflammation and autoimmunity are also addressed.

The phytol-based adjuvants hold great promise for improving vaccine efficacy, as they cause little or no persistent inflammation, but are highly effective in stimulating a multifaceted immune response, characterized by proficient recruitment of immune cells, generation of antibody and immunological memory, and activation of both Th1 and Th2 responses. Future focus will be on developing cocktail adjuvants to activate the complement system, mobilize follicular T helper cells as well as NKT and γδ T cells and activate cross-presenting dendritic cells to stimulate CD8(+) effector T cells.