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

• Published in: iScience Vol. 26; no. 12; p. 108574
• Main Authors: Vianello, Eleonora, Persson, Josefine, Andersson, Björn, van Veen, Suzanne, Dias, Thomaz Lüscher, Santoro, Francesco, Östensson, Malin, Obudulu, Ogonna, Agbajogu, Christopher, Torkzadeh, Sara, Agnandji, Selidji Todagbe, Ahmed, Rafi, Anderson, Jenna, Auderset, Floriane, Bejon, Philip, Borgianni, Luisa, Brosnahan, Jessica, Ciabattini, Annalisa, Engler, Olivier, Haks, Marielle C., Harandi, Ali M., Heppner, Donald Gray, Gerlini, Alice, Huttner, Angela, Kremsner, Peter G., Medaglini, Donata, Monath, Thomas, Ndungu, Francis, Njuguna, Patricia, Ottenhoff, Tom H.M., Pejoski, David, Page, Mark, Pozzi, Gianni, Siegrist, Claire-Anne, Dubey, Sheri, Eichberg, Micheal J., Gonzalez-Dias, Patrícia, Essone, Paulin Ndong, Kabwende, Lumeka, Kremsner, Peter Gottfried, Nakaya, Helder, Nakka, Sravya S., Haks, Mariëlle C., Rothenberger, Sylvia, Nakaya, Helder I.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.12.2023; Elsevier
• Subjects: Health sciences; Immunologi inom det medicinska området; Immunology; Immunology in the medical area; Molecular biology; Virology; Health sciences; Immunology; Molecular biology; Virology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.108574

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. [Display omitted] •RVSV-ZEBOV-GP vaccination modulates human blood intracellular and circulating miRNome•Baseline and early post-vaccination miRNAs correlate with IgG antibody responses•Early post-vaccination miRNA signatures predict D28 and D360 IgG antibody levels•An eight-miRNA signature correlates with immune-related target mRNAs and pathways Health sciences; Molecular biology; Immunology; Virology