Different human vaccine adjuvants promote distinct antigen-independent immunological signatures tailored to different pathogens.

The majority of vaccine candidates in clinical development are highly purified proteins and peptides relying on adjuvantsto enhance and/or direct immune responses. Despite the acknowledged need for novel adjuvants, there are still very few adjuvantsin licensed human vaccines. A vast number of adjuvantshave been tested pre-clinically using different experimental conditions, rendering it impossible to directly compare their activity. We performed a head-to-head comparison of five different adjuvants Alum, MF59®, GLA-SE, IC31® and CAF01 in mice and combined these with antigens from M. tuberculosis, influenza, and chlamydiato test immune-profiles and efficacy in infection models using standardized protocols. Regardless of antigen, each adjuvanthad a unique immunological signature suggesting that the adjuvantshave potential for different disease targets. Alumincreased antibody titers; MF59® induced strong antibody and IL-5 responses; GLA-SE induced antibodies and Th1; CAF01 showed a mixed Th1/Th17 profile and IC31® induced strong Th1 responses. MF59® and GLA-SE were strong inducers of influenza HI titers while CAF01, GLA-SE and IC31® enhanced protection to TB and chlamydia. Importantly, this is the first extensive attempt to categorize clinical-grade adjuvantsbased on their immune profiles and protective efficacy to inform a rational development of next generation vaccines for human use.