Human Transcriptomic Response to the VSV-Vectored Ebola Vaccine

Abstract

Ebolavirus Disease (EVD) is a severe haemorrhagic fever that occurs in epidemic outbreaks, with a high fatality rate and no specific therapies available. rVSVΔG-ZEBOV-GP (Ervebo®), a live-attenuated recombinant vesicular stomatitis virus vector expressing the glycoprotein G of Zaire Ebolavirus, is the first vaccine approved for prevention of EVD. Both innate and adaptive responses are deemed to be involved in vaccine-induced protection, yet the mechanisms are not fully elucidated. A global transcriptomic approach was used to profile the blood host-response in 51 healthy volunteers enrolled in a phase 1/2 clinical trial. Signatures of the host responses were investigated assessing the enrichment in differentially expressed genes (DEGs) of specific “blood transcription modules” (BTM). Comparison of gene-expression levels showed that vaccination produces a peak of 5469 DEGs at day one, representing 38.6% of the expressed genes. Out of 346 BTMs, 144 were significantly affected by vaccination. Innate immunity pathways were induced from day 1 to day 14. At days 2 and 3, neutrophil modules were downregulated and complement-related modules upregulated. T-cell and cell-cycle associated modules were upregulated at days 7 and 14, while at day 28, no modules remained activated. At day 14, a direct correlation was observed between ZEBOV glycoprotein-specific antibody titres and activation of seven BTMs, including two related to B-cell activation and B cell receptor signalling. Transcriptomic analysis identified an rVSVΔG-ZEBOV-GP-induced signature and demonstrated a direct correlation of blood transcriptomic changes with ZEBOV glycoprotein-specific antibody titres.

Single Dose of a VSV-Based Vaccine Rapidly Protects Macaques From Marburg Virus Disease

“…Several ISGs, Dead Box helicases and nucleic acid sensors were acutely induced 3 DPV. Interestingly, this induction was less robust than that observed for VSV-EBOV as indicated by data presented here and published elsewhere (29)(30)(31). In contrast, antiviral innate immune responses in control animals and those that succumb to infection are progressively amplified as disease progresses and are associated with adverse outcomes and high mortality both in NHP and humans (3,4,16,(32)(33)(34)(35).…”

Immune Memory After Respiratory Infection With Streptococcus pneumoniae Is Revealed by in vitro Stimulation of Murine Splenocytes With Inactivated Pneumococcal Whole Cells: Evidence of Early Recall Responses by Transcriptomic Analysis

“…Library preparation was performed as described in a previous publication ( Santoro et al., 2021 ), using the Ion AmpliSeq™ Transcriptome Mouse Gene Expression Kit from AmpliSeq (Thermo Fisher Scientific), allowing the amplification of 23,930 target genes. Libraries were diluted to 50 pM and pooled in equal volumes (7 μl), with eight individual samples per pool and loaded onto Ion PI™ Chip v3 using the Ion Chef™ Instrument.…”

Nonhuman Primates Are Protected against Marburg Virus Disease by Vaccination with a Vesicular Stomatitis Virus Vector-Based Vaccine Prepared under Conditions to Allow Advancement to Human Clinical Trials

“…The success of the EBOV vaccine produced by Merck Vaccines (rVSV∆G-ZEBOV-GP, marketed as ERVEBO ® ) has provided a strong rationale for efforts to develop other vaccines based on recombinant vesicular stomatitis virus (rVSV) vaccine vector technology [ 12 , 13 , 14 ]. The performance of ERVEBO ® in outbreak environments has clearly shown that the VSV-based technology has multiple features needed for development of other effective filovirus vaccines including, (1) acceptable safety and tolerability; (2) high efficacy after a single dose; and (3) rapid development of protective immunity [ 12 , 13 , 14 , 15 , 16 ].…”