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Characterization of potential biomarkers of reactogenicity of licensed antiviral vaccines: randomized controlled clinical trials conducted by the BIOVACSAFE consortium
- Source :
- Scientific Reports, Vol 9, Iss 1, Pp 1-14 (2019), Scientific Reports
- Publication Year :
- 2019
- Publisher :
- Nature Publishing Group, 2019.
-
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.
- Subjects :
- 0301 basic medicine
Trivalent influenza vaccine
Adult
Male
Hepatitis B vaccine
Transcription, Genetic
Lymphocyte
lcsh:Medicine
Predictive markers
Virus
Article
03 medical and health sciences
Young Adult
0302 clinical medicine
medicine
Humans
lcsh:Science
Vaccines
Multidisciplinary
Reactogenicity
Hematologic Tests
business.industry
Vital Signs
Vaccination
lcsh:R
Viral Vaccines
3. Good health
Clinical trial
030104 developmental biology
medicine.anatomical_structure
Immunization
Immunology
Cytokines
Female
lcsh:Q
Symptom Assessment
business
030217 neurology & neurosurgery
Biomarkers
Acute-Phase Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....6fb82a2ccd27deedea20670fbdf7b86c