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Different human vaccine adjuvants promote distinct antigenin-dependent immunological signatures tailored to different pathogens

Journal article
Authors N. P. H. Knudsen
A. Olsen
C. Buonsanti
F. Follmann
Yuan Zhang
R. N. Coler
C. B. Fox
A. Meinke
U. D. Oro
D. Casini
A. Bonci
R. Billeskov
E. De Gregorio
R. Rappuoli
Ali M Harandi
P. Andersen
E. M. Agger
Published in Scientific Reports
Volume 6
Pages Article number: 19570
ISSN 2045-2322
Publication year 2016
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Pages Article number: 19570
Language en
Links dx.doi.org/10.1038/srep19570
Keywords in-water emulsion, cd4(+) t-cells, mycobacterium-tuberculosis infection, humoral immune-responses, chlamydia-trachomatis, influenza vaccine, subunit vaccine, protective immunity, pandemic influenza, h5n1 vaccine
Subject categories Clinical Medicine

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 (R), GLA-SE, IC31 (R) 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 (R) induced strong antibody and IL-5 responses; GLA-SE induced antibodies and Th1; CAF01 showed a mixed Th1/Th17 profile and IC31 (R) induced strong Th1 responses. MF59 (R) and GLA-SE were strong inducers of influenza HI titers while CAF01, GLA-SE and IC31 (R) 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.

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