title: Different human vaccine adjuvants promote distinct antigen-independent immunological signatures tailored to different pathogens.
abstract: The majority of vaccine candidates in clinical development are highly purified proteins and peptides relying on adjuvants to enhance and/or direct immune responses. Despite the acknowledged need for novel adjuvants, there are still very few adjuvants in licensed human vaccines. A vast number of adjuvants have 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 chlamydia to test immune-profiles and efficacy in infection models using standardized protocols. Regardless of antigen, each adjuvant had a unique immunological signature suggesting that the adjuvants have potential for different disease targets. Alum increased 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 adjuvants based on their immune profiles and protective efficacy to inform a rational development of next generation vaccines for human use.
authors.affiliation: Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Niels Peter H
authors.initials: NP
authors.lastname: Knudsen
authors.affiliation: Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Anja
authors.initials: A
authors.lastname: Olsen
authors.affiliation: Novartis Vaccines and Diagnostics s.r.l (a GSK Company), Siena, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Buonsanti
authors.affiliation: Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Frank
authors.initials: F
authors.lastname: Follmann
authors.affiliation: Department of Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Infectious Disease Research Institute, Seattle, WA, USA.
authors.forename: Rhea N
authors.initials: RN
authors.lastname: Coler
authors.affiliation: Infectious Disease Research Institute, Seattle, WA, USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Fox
authors.affiliation: Valneva Austria GmbH, Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinke
authors.affiliation: Novartis Vaccines and Diagnostics s.r.l (a GSK Company), Siena, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: D'Oro
authors.affiliation: Novartis Vaccines and Diagnostics s.r.l (a GSK Company), Siena, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Casini
authors.affiliation: Novartis Vaccines and Diagnostics s.r.l (a GSK Company), Siena, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bonci
authors.affiliation: Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Rolf
authors.initials: R
authors.lastname: Billeskov
authors.affiliation: Novartis Vaccines and Diagnostics s.r.l (a GSK Company), Siena, Italy.
authors.forename: Ennio
authors.initials: E
authors.lastname: De Gregorio
authors.affiliation: Novartis Vaccines and Diagnostics s.r.l (a GSK Company), Siena, Italy.
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.affiliation: Department of Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Ali M
authors.initials: AM
authors.lastname: Harandi
authors.affiliation: Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
authors.affiliation: Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Else Marie
authors.initials: EM
authors.lastname: Agger
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D002690:Chlamydia Infections / Q000276:immunology / Q000517:prevention & control; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control; D014611:Vaccination; D014612:Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D000941:Antigens; D016207:Cytokines; D014612:Vaccines