Different Adjuvants Induce Common Innate Pathways That Are Associated with Enhanced Adaptive Responses against a Model Antigen in Humans

• Published in: Frontiers in immunology 2017-08, Vol.8, p.943-943
• Main Authors: Burny, Wivine, Callegaro, Andrea, Bechtold, Viviane, Clement, Frédéric, Delhaye, Sophie, Fissette, Laurence, Janssens, Michel, Leroux-Roels, Geert, Marchant, Arnaud, van den Berg, Robert A, Garçon, Nathalie, van der Most, Robbert, Didierlaurent, Arnaud M
• Format: Article
• Language: English
• Subjects: adaptive immune response; AS01; AS03; AS04; Immunology; innate immune response; vaccine adjuvants
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2017.00943

To elucidate the role of innate responses in vaccine immunogenicity, we compared early responses to hepatitis B virus (HBV) surface antigen (HBsAg) combined with different Adjuvant Systems (AS) in healthy HBV-naïve adults, and included these parameters in multi-parametric models of adaptive responses. A total of 291 participants aged 18-45 years were randomized 1:1:1:1:1 to receive HBsAg with AS01 , AS01 , AS03, AS04, or Alum/Al(OH) at days 0 and 30 (ClinicalTrials.gov: NCT00805389). Blood protein, cellular, and mRNA innate responses were assessed at early time-points and up to 7 days after vaccination, and used with reactogenicity symptoms in linear regression analyses evaluating their correlation with HBs-specific CD4 T-cell and antibody responses at day 44. All AS induced transient innate responses, including interleukin (IL)-6 and C-reactive protein (CRP), mostly peaking at 24 h post-vaccination and subsiding to baseline within 1-3 days. After the second but not the first injection, median interferon (IFN)-γ levels were increased in the AS01 group, and IFN-γ-inducible protein-10 levels and IFN-inducible genes upregulated in the AS01 and AS03 groups. No distinct marker or signature was specific to one particular AS. Innate profiles were comparable between AS01 , AS01 , and AS03 groups, and between AS04 and Alum groups. AS group rankings within adaptive and innate response levels and reactogenicity prevalence were similar (AS01  ≥ AS01  > AS03 > AS04 > Alum), suggesting an association between magnitudes of inflammatory and vaccine responses. Modeling revealed associations between adaptive responses and specific traits of the innate response post-dose 2 (activation of the IFN-signaling pathway, CRP and IL-6 responses). In conclusion, the ability of AS01 and AS03 to enhance adaptive responses to co-administered HBsAg is likely linked to their capacity to activate innate immunity, particularly the IFN-signaling pathway.