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

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 stra...

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Published inScientific reports Vol. 9; no. 1; pp. 20362 - 14
Main Authors 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
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 30.12.2019
Nature Publishing Group
Subjects
38/61
631/250/590
692/53/2423
Acute-Phase Proteins
Adult
Antiviral drugs
Biomarkers
Blood
Clinical trials
Cytokines - blood
Female
Genes
Heart rate
Hematologic Tests
Hepatitis B
Humanities and Social Sciences
Humans
Immunization
Immunological memory
Inflammation
Influenza
Interferon
IP-10 protein
Lymphocytes
Male
Monocytes
multidisciplinary
Physiology
Public health
Science
Science (multidisciplinary)
Symptom Assessment
Transcription activation
Transcription, Genetic
Vaccination - adverse effects
Vaccination - methods
Vaccine development
Vaccines
Varicella
Viral Vaccines - adverse effects
Viral Vaccines - immunology
Vital Signs
Young Adult
Online AccessGet full text
ISSN2045-2322
2045-2322
DOI10.1038/s41598-019-56994-8

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Abstract 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 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.
AbstractList 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 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.
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 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.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 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.
ArticleNumber 20362
Author Del Giudice, Giuseppe
Weiner, January
Maertzdorf, Jeroen
Kester, Kent E.
Bottazzi, Barbara
Mantovani, Alberto
Kaufmann, Stefan H. E.
Greenwood, Aldona
Jonsdottir, Ingileif
Pizzoferro, Kat
Linley, Catherine
Denoel, Philippe
Bodinham, Caroline
Leroux-Roels, Geert
Mollenkopf, Hans-Joachim
van den Berg, Robert
Lewis, David J. M.
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  doi: 10.1073/pnas.1519690113
– volume: 17
  start-page: 204
  year: 2016
  ident: 56994_CR3
  publication-title: Nat. Immunol.
  doi: 10.1038/ni.3328
– volume: 37
  start-page: 2004
  year: 2019
  ident: 56994_CR4
  publication-title: Vaccine
  doi: 10.1016/j.vaccine.2019.02.015
– volume: 180
  start-page: 5402
  year: 2008
  ident: 56994_CR24
  publication-title: J. Immunol.
  doi: 10.4049/jimmunol.180.8.5402
– volume: 15
  start-page: 195
  year: 2014
  ident: 56994_CR19
  publication-title: Nat. Immunol.
  doi: 10.1038/ni.2789
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Snippet Biomarkers predictive of inflammatory events post-vaccination could accelerate vaccine development. Within the BIOVACSAFE framework, we conducted three...
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SubjectTerms 38/61
631/250/590
692/53/2423
Acute-Phase Proteins
Adult
Antiviral drugs
Biomarkers
Blood
Clinical trials
Cytokines - blood
Female
Genes
Heart rate
Hematologic Tests
Hepatitis B
Humanities and Social Sciences
Humans
Immunization
Immunological memory
Inflammation
Influenza
Interferon
IP-10 protein
Lymphocytes
Male
Monocytes
multidisciplinary
Physiology
Public health
Science
Science (multidisciplinary)
Symptom Assessment
Transcription activation
Transcription, Genetic
Vaccination - adverse effects
Vaccination - methods
Vaccine development
Vaccines
Varicella
Viral Vaccines - adverse effects
Viral Vaccines - immunology
Vital Signs
Young Adult
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Title Characterization of potential biomarkers of reactogenicity of licensed antiviral vaccines: randomized controlled clinical trials conducted by the BIOVACSAFE consortium
URI https://link.springer.com/article/10.1038/s41598-019-56994-8
https://www.ncbi.nlm.nih.gov/pubmed/31889148
https://www.proquest.com/docview/2331419272
https://www.proquest.com/docview/2331634125
https://pubmed.ncbi.nlm.nih.gov/PMC6937244
Volume 9
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