par Burny, Wivine ;Callegaro, Andrea;Bechtold, Viviane;Clément, Frédéric;Delhaye, Sophie;Fissette, Laurence;Janssens, Michel;Leroux-Roels, Geert;Marchant, Arnaud ;van den Berg, Robert R.A.;Garçon, Nathalie;van der Most, Robbert;Didierlaurent, Arnaud M;Carletti, Isabelle;Esen, Meral;Gabor, Julian Justin;Haelterman, Edwige;Hervé, Caroline;Horsmans, Y.;Janssens, Michel;Kremsner, Peter Gottfried Gottfried P.G.;Moris, Philippe;Schwarz, Tino F;da Silva, Fernanda Tavares;Van Belle, Pascale;Van Damme, Pierre;Zuchner, Dirk
Référence Frontiers in immunology, 8, AUG, 943
Publication Publié, 2017-08
Référence Frontiers in immunology, 8, AUG, 943
Publication Publié, 2017-08
Article révisé par les pairs
Résumé : | 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 AS01B , AS01E , AS03, AS04, or Alum/ Al(OH)3 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 AS01B 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 AS01B , AS01E , and AS03 groups, and between AS04 and Alum groups. AS group rankings within adaptive and innate response levels and reactogenicity prevalence were similar (AS01B ≥ AS01E > 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. |