tetano
Editor, Senior Moderator
Sci Rep. 2019 Dec 30;9(1):20362. doi: 10.1038/s41598-019-56994-8. [h=1]Characterization of potential biomarkers of reactogenicity of licensed antiviral vaccines: randomized controlled clinical trials conducted by the BIOVACSAFE consortium.[/h]
Weiner J[SUP]1,[/SUP][SUP]2[/SUP], Lewis DJM[SUP]3[/SUP], Maertzdorf J[SUP]1[/SUP], Mollenkopf HJ[SUP]1[/SUP], Bodinham C[SUP]3[/SUP], Pizzoferro K[SUP]3[/SUP], Linley C[SUP]3[/SUP], Greenwood A[SUP]3[/SUP], Mantovani A[SUP]4,[/SUP][SUP]5,[/SUP][SUP]6[/SUP], Bottazzi B[SUP]3[/SUP], Denoel P[SUP]7[/SUP], Leroux-Roels G[SUP]8[/SUP], Kester KE[SUP]9[/SUP], Jonsdottir I[SUP]10[/SUP], van den Berg R[SUP]11[/SUP], Kaufmann SHE[SUP]1[/SUP], Del Giudice G[SUP]12[/SUP].
[h=3]Author information[/h] 1 Max Planck Institute for Infection Biology (MPIIB), Department for Immunology, Berlin, Germany. 2 Core Unit Bioinformatics, Berlin Institute of Health, Berlin, Germany. 3 Surrey Clinical Research Centre, University of Surrey, Guildford, UK. 4 Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy. 5 Humanitas University, Pieve Emanuele, Italy. 6 The William Harvey Research Institute, Queen Mary University of London, London, UK. 7 GSK, Rixensart, Belgium. 8 Center for Vaccinology, Ghent University and University Hospital, Ghent, Belgium. 9 Sanofi-Pasteur, Swiftwater, PA, USA. 10 deCODE genetics/Amgen Inc., Reykjavik, Iceland. 11 GSK, Rockville, MD, USA. 12 GSK, Siena, Italy. giuseppe.x.del-giudice@gsk.com.
[h=3]Abstract[/h] Biomarkers 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 na?ve 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.
PMID: 31889148 DOI: 10.1038/s41598-019-56994-8
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Weiner J[SUP]1,[/SUP][SUP]2[/SUP], Lewis DJM[SUP]3[/SUP], Maertzdorf J[SUP]1[/SUP], Mollenkopf HJ[SUP]1[/SUP], Bodinham C[SUP]3[/SUP], Pizzoferro K[SUP]3[/SUP], Linley C[SUP]3[/SUP], Greenwood A[SUP]3[/SUP], Mantovani A[SUP]4,[/SUP][SUP]5,[/SUP][SUP]6[/SUP], Bottazzi B[SUP]3[/SUP], Denoel P[SUP]7[/SUP], Leroux-Roels G[SUP]8[/SUP], Kester KE[SUP]9[/SUP], Jonsdottir I[SUP]10[/SUP], van den Berg R[SUP]11[/SUP], Kaufmann SHE[SUP]1[/SUP], Del Giudice G[SUP]12[/SUP].
[h=3]Author information[/h] 1 Max Planck Institute for Infection Biology (MPIIB), Department for Immunology, Berlin, Germany. 2 Core Unit Bioinformatics, Berlin Institute of Health, Berlin, Germany. 3 Surrey Clinical Research Centre, University of Surrey, Guildford, UK. 4 Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy. 5 Humanitas University, Pieve Emanuele, Italy. 6 The William Harvey Research Institute, Queen Mary University of London, London, UK. 7 GSK, Rixensart, Belgium. 8 Center for Vaccinology, Ghent University and University Hospital, Ghent, Belgium. 9 Sanofi-Pasteur, Swiftwater, PA, USA. 10 deCODE genetics/Amgen Inc., Reykjavik, Iceland. 11 GSK, Rockville, MD, USA. 12 GSK, Siena, Italy. giuseppe.x.del-giudice@gsk.com.
[h=3]Abstract[/h] Biomarkers 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 na?ve 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.
PMID: 31889148 DOI: 10.1038/s41598-019-56994-8
Free full text