Global blood miRNA profiling unravels early signatures of immunogenicity of Ebola vaccine rVSVΔG-ZEBOV-GP

Eleonora Vianello; Josefine Persson; Björn Andersson; Suzanne van Veen; Thomaz Lüscher Dias; Francesco Santoro; Malin Östensson; Ogonna Obudulu; Christopher Agbajogu; Sara Torkzadeh; VSV-EBOVAC; VSV-EBOPLUS Consortia; Helder I Nakaya; Donata Medaglini; Claire-Anne Siegrist; Tom H M Ottenhoff; Ali M Harandi

doi:10.1016/j.isci.2023.108574

Global blood miRNA profiling unravels early signatures of immunogenicity of Ebola vaccine rVSVΔG-ZEBOV-GP

iScience. 2023 Nov 23;26(12):108574. doi: 10.1016/j.isci.2023.108574. eCollection 2023 Dec 15.

Authors

Eleonora Vianello¹, Josefine Persson², Björn Andersson³, Suzanne van Veen¹, Thomaz Lüscher Dias⁴, Francesco Santoro⁵, Malin Östensson³, Ogonna Obudulu², Christopher Agbajogu², Sara Torkzadeh²; VSV-EBOVAC; VSV-EBOPLUS Consortia; Helder I Nakaya⁶, Donata Medaglini⁵, Claire-Anne Siegrist⁷, Tom H M Ottenhoff¹, Ali M Harandi^{2

8}

Collaborators

Selidji Todagbe Agnandji, Rafi Ahmed, Jenna Anderson, Floriane Auderset, Philip Bejon, Luisa Borgianni, Jessica Brosnahan, Annalisa Ciabattini, Olivier Engler, Marielle C Haks, Ali M Harandi, Donald Gray Heppner, Alice Gerlini, Angela Huttner, Peter G Kremsner, Donata Medaglini, Thomas Monath, Francis Ndungu, Patricia Njuguna, Tom Hm Ottenhoff, David Pejoski, Mark Page, Gianni Pozzi, Francesco Santoro, Claire-Anne Siegrist, Selidji Todagbe Agnandji, Luisa Borgianni, Annalisa Ciabattini, Sheri Dubey, Micheal J Eichberg, Olivier Engler, Patrícia Gonzalez-Dias, Paulin Ndong Essone, Ali M Harandi, Alice Gerlini, Angela Huttner, Lumeka Kabwende, Peter Gottfried Kremsner, Donata Medaglini, Helder Nakaya, Sravya S Nakka, Tom Hm Ottenhoff, Mariëlle C Haks, Josefine Persson, Gianni Pozzi, Sylvia Rothenberger, Francesco Santoro, Claire-Anne Siegrist, Suzanne van Veen, Eleonora Vianello

Affiliations

¹ Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands.
² Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
³ Bioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁴ Scientific Platform Pasteur-University of São Paulo, São Paulo, Brazil.
⁵ Department of Medical Biotechnologies, University of Siena, Italy.
⁶ Hospital Israelita Albert Einstein, São Paulo, Brazil.
⁷ Centre for Vaccinology, University Hospitals of Geneva and Faculty of Medicine, Geneva, Switzerland.
⁸ Vaccine Evaluation Center, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada.

Abstract

The vectored Ebola vaccine rVSVΔG-ZEBOV-GP elicits protection against Ebola Virus Disease (EVD). In a study of forty-eight healthy adult volunteers who received either the rVSVΔG-ZEBOV-GP vaccine or placebo, we profiled intracellular microRNAs (miRNAs) from whole blood cells (WB) and circulating miRNAs from serum-derived extracellular vesicles (EV) at baseline and longitudinally following vaccination. Further, we identified early miRNA signatures associated with ZEBOV-specific IgG antibody responses at baseline and up to one year post-vaccination, and pinpointed target mRNA transcripts and pathways correlated to miRNAs whose expression was altered after vaccination by using systems biology approaches. Several miRNAs were differentially expressed (DE) and miRNA signatures predicted high or low IgG ZEBOV-specific antibody levels with high classification performance. The top miRNA discriminators were WB-miR-6810, EV-miR-7151-3p, and EV-miR-4426. An eight-miRNA antibody predictive signature was associated with immune-related target mRNAs and pathways. These findings provide valuable insights into early blood biomarkers associated with rVSVΔG-ZEBOV-GP vaccine-induced IgG antibody responses.

Keywords: Health sciences; Immunology; Molecular biology; Virology.