Transcriptional changes in macaques immunized with the rVSV-Filo VesiculoVax quadrivalent vaccine and exposed to Marburg virus (MARV), Ebola virus (EBOV), Sudan virus (SUDV), or Bundibugyo virus (BDBV) 1 week after immunization. A, Heat maps of the most up-regulated (left) and down-regulated (right) messenger RNAs (mRNAs) in vaccinated subjects—including EBOV survivors (ES; n = 4; E1, E3, E4, and E5), an EBOV fatal case (EF; n = 1; E2), MARV survivors (MS; n = 5; M1, M2, M3, M4, and M5), SUDV survivors (SS; n = 5; S1, S2, S3, S4, and S5), and BDBV survivors (BS; n = 5; B1, B2, B3, B4, and B5)—versus the corresponding vector controls for EBOV (EC), MARV (MC), SUDV (SC), and BDBV (BC) for each virus challenge at 0, 3, and 6 days post infection (DPI) (Supplementary Data 1). The data set was filtered by the ES group at 6 DPI, in order of statistical significance. B, Enrichment of up-regulated (left) or down regulated (right) differentially expressed transcripts in rVSV-Filo–vaccinated survivors at 6 DPI irrespective of challenge virus. Any differentially expressed transcript with a Benjamini-Hochberg false discovery rate–corrected P value <.05 was deemed significant; up-regulated transcripts were classified by a >1.5 log₂ ratio fold change, and down-regulated transcripts by a <−1.5 log₂ ratio fold change. Pathways are sorted by statistical significance. Abbreviations: COVID-19, coronavirus disease 2019; NOD, nucleotide oligomerization domain; NFAT TFPATHWAY, calcineurin-regulated nuclear factor of activated T-cells (NFAT)-dependent transcription factor in lymphocytes; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; Th17, T-helper 17; TNF, tumor necrosis factor. C, Volcano plots displaying overall −log₁₀ (P values) and log₂ fold changes for each mRNA target filtered by disposition in survivors (n = 19) versus fatal cases (n = 5), irrespective of time point and challenge virus. D, Immune cell type profiling based on transcriptional changes in survivor versus fatal subjects irrespective of challenge virus and time point. Abbreviations: NK, natural killer; Th1, T-helper 1.