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Weiner, January; Lewis, David J. M.; Maertzdorf, Jeroen; Mollenkopf, Hans-Joachim; Bodinham, Caroline; Pizzoferro, Kat; Linley, Catherine; Greenwood, Aldona; Mantovani, Alberto; Bottazzi, Barbara; Denoel, Philippe; Leroux-Roels, Geert; Kester, Kent E.; Jonsdottir, Ingileif; van den Berg, Robert; Kaufmann, Stefan H. E.; Del Giudice, Giuseppe

Characterization of potential biomarkers of reactogenicity of licensed antiviral vaccines: randomized controlled clinical trials conducted by the BIOVACSAFE consortium

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  • Media type: E-Article
  • Title: Characterization of potential biomarkers of reactogenicity of licensed antiviral vaccines: randomized controlled clinical trials conducted by the BIOVACSAFE consortium
  • Contributor: Weiner, January; Lewis, David J. M.; Maertzdorf, Jeroen; Mollenkopf, Hans-Joachim; Bodinham, Caroline; Pizzoferro, Kat; Linley, Catherine; Greenwood, Aldona; Mantovani, Alberto; Bottazzi, Barbara; Denoel, Philippe; Leroux-Roels, Geert; Kester, Kent E.; Jonsdottir, Ingileif; van den Berg, Robert; Kaufmann, Stefan H. E.; Del Giudice, Giuseppe
  • Published: Springer Science and Business Media LLC, 2019
  • Published in: Scientific Reports, 9 (2019) 1
  • Language: English
  • DOI: 10.1038/s41598-019-56994-8
  • ISSN: 2045-2322
  • Origination:
  • Footnote:
  • Description: AbstractBiomarkers predictive of inflammatory events post-vaccination could accelerate vaccine development. Within the BIOVACSAFE framework, we conducted three identically designed, placebo-controlled inpatient/outpatient clinical studies (NCT01765413/NCT01771354/NCT01771367). Six antiviral vaccination strategies were evaluated to generate training data-sets of pre-/post-vaccination vital signs, blood changes and whole-blood gene transcripts, and to identify putative biomarkers of early inflammation/reactogenicity that could guide the design of subsequent focused confirmatory studies. Healthy adults (N = 123; 20–21/group) received one immunization at Day (D)0. Alum-adjuvanted hepatitis B vaccine elicited vital signs and inflammatory (CRP/innate cells) responses that were similar between primed/naive vaccinees, and low-level gene responses. MF59-adjuvanted trivalent influenza vaccine (ATIV) induced distinct physiological (temperature/heart rate/reactogenicity) response-patterns not seen with non-adjuvanted TIV or with the other vaccines. ATIV also elicited robust early (D1) activation of IFN-related genes (associated with serum IP-10 levels) and innate-cell-related genes, and changes in monocyte/neutrophil/lymphocyte counts, while TIV elicited similar but lower responses. Due to viral replication kinetics, innate gene activation by live yellow-fever or varicella-zoster virus (YFV/VZV) vaccines was more suspended, with early IFN-associated responses in naïve YFV-vaccine recipients but not in primed VZV-vaccine recipients. Inflammatory responses (physiological/serum markers, innate-signaling transcripts) are therefore a function of the vaccine type/composition and presence/absence of immune memory. The data reported here have guided the design of confirmatory Phase IV trials using ATIV to provide tools to identify inflammatory or reactogenicity biomarkers.
  • Access State: Open Access