Table 1.
Neutralization titers (IRNT80 or PRNT801) for SAB TcpAb preparations.
Table 2.
Characteristics and study design for Cohort 1 and Cohort 2 animals.
Fig 1.
Timeline of macaque baseline telemetry.
SAB-131 treatment, bleeding and tissue harvesting for cohort 1 (A) and cohort 2 (B) animals.
Fig 2.
Febrile responses for cohort 1.
Actual (red lines) and forecasted (black lines) temperature telemetry data from cohort 1 cynomolgus macaques challenged with VEEV TrD and either treated with control liquid TcpAb (row A) or treated with liquid anti-VEEV TcpAb 24 hours prior to infection (Pre) or 24 hours after infection (Post). Shaded areas represent the first and second febrile phases determined a previous study [28]. Forecast temperatures are calculated with NCSS-PASS Software based upon the at least 3 days of data recorded prior to challenge. The number above each temperature profile corresponds to the unique identification number of the macaque.
Fig 3.
Febrile responses for cohort 2.
Actual (red lines) and forecasted (black lines) temperature telemetry data from cohort 2 cynomolgus macaques challenged with VEEV INH9813-K3E and either treated 24 hours prior to challenge with control TcpAb (Control, n = 3), intranasal lyophilized SAB-131 (Ly-IN, n = 5), intravenous liquid SAB-131 (Lq-IV, n = 3), or intranasal lyophilized and intravenous liquid SAB-131 (Ly-IN+Lq-IV, n = 3). Shaded areas represent the first and second febrile phases determined a previous study [28]. Forecast temperatures are calculated with NCSS-PASS software based upon at least 3 days of data recorded prior to challenge. The number above each temperature profile corresponds to the unique identification number of the macaque.
Table 3.
Mean values for macaque fever responses in control and treatment groups.
Table 4.
Detection of infectious virus in sera of cohort 1 and cohort 2 macaques treated with irrelevant or anti-VEEV TcpAb preparations either before or after aerosol infection with VEEV.
Table 5.
Quantitation of viral genomes detected by qRT-PCT in sera of cohort 1 and cohort 2 macaques treated with irrelevant or anti-VEEV TcpAb preparations either before or after aerosol infection with VEEV.
Fig 4.
Averaged fever hours (differences between predicted and actual temperature) by day post challenge for cohort 1 (A) or cohort 2 (B) NHPs treated with control Abs or pre- or post-treated with anti-VEEV TcpAb. Mean and SEM are presented.
Fig 5.
Serum plaque (A) and qRT-PCR genome equivalent (B) titers for cohort 1 macaques. Serum plaque (C) and qRT-PCR genome equivalent (D) titers for cohort 2 macaques. Median values for plaque titers and median geometric mean genome equivalent (GE) titers for qRT-PCR are shown. Error bars are omitted for clarity.
Fig 6.
CBC analysis of VEEV-infected macaques.
Median percent change from Day = 0 for white blood cell (A,B), lymphocyte (C,D) and granulocyte (E,F) counts for cohort 1 (A, C, E) or cohort 2 (B, D, F) animals at two-day intervals after challenge (n = 3, except cohort 2 Ly-IN group of n = 5). Error bars are omitted for clarity.
Fig 7.
Cytokine induction in plasma from cohort 2 macaques.
Data from multiple uninfected macaques [28] were used to determine a normal range as indicated by the shaded area bound by dotted lines. Significance differences, determined by two-way ANOVA with Dunnett’s post-test (*: p < 0.05, **: p < 0.01, ***: p < 0.001), are colored for each treatment group and compare each treatment group with the control group. Error bars are standard deviations and only upper bars are shown for clarity.
Fig 8.
Histological analysis of cohort 1 macaques.
(A) Histopathology ordinal scores for the six distinct anatomical regions of the brain from cohort 1 animals (n = 3/treatment). All animals were euthanized at 28 dpi. Hematoxylin and eosin (H&E) stained sections were generated blinded to study conditions. (B) Representative photomicrographs of H&E sections from the frontal lobes of VEEV TrD-infected control (A-C), pre-treated (D-F) and post-treated (G-I) cohort 1 macaques. Scale bars = 50μm.