Data_Sheet_2_Herd Immunity to Ebolaviruses Is Not a Realistic Target for Current Vaccination Strategies.PDF

<p>The recent West African Ebola virus pandemic, which affected >28,000 individuals increased interest in anti-Ebolavirus vaccination programs. Here, we systematically analyzed the requirements for a prophylactic vaccination program based on the basic reproductive number (R₀, i.e., the number of secondary cases that result from an individual infection). Published R₀ values were determined by systematic literature research and ranged from 0.37 to 20. R₀s ≥ 4 realistically reflected the critical early outbreak phases and superspreading events. Based on the R₀, the herd immunity threshold (I_c) was calculated using the equation I_c = 1 − (1/R₀). The critical vaccination coverage (V_c) needed to provide herd immunity was determined by including the vaccine effectiveness (E) using the equation V_c = I_c/E. At an R₀ of 4, the I_c is 75% and at an E of 90%, more than 80% of a population need to be vaccinated to establish herd immunity. Such vaccination rates are currently unrealistic because of resistance against vaccinations, financial/logistical challenges, and a lack of vaccines that provide long-term protection against all human-pathogenic Ebolaviruses. Hence, outbreak management will for the foreseeable future depend on surveillance and case isolation. Clinical vaccine candidates are only available for Ebola viruses. Their use will need to be focused on health-care workers, potentially in combination with ring vaccination approaches.</p

Data_Sheet_4_Herd Immunity to Ebolaviruses Is Not a Realistic Target for Current Vaccination Strategies.PDF

<p>The recent West African Ebola virus pandemic, which affected >28,000 individuals increased interest in anti-Ebolavirus vaccination programs. Here, we systematically analyzed the requirements for a prophylactic vaccination program based on the basic reproductive number (R₀, i.e., the number of secondary cases that result from an individual infection). Published R₀ values were determined by systematic literature research and ranged from 0.37 to 20. R₀s ≥ 4 realistically reflected the critical early outbreak phases and superspreading events. Based on the R₀, the herd immunity threshold (I_c) was calculated using the equation I_c = 1 − (1/R₀). The critical vaccination coverage (V_c) needed to provide herd immunity was determined by including the vaccine effectiveness (E) using the equation V_c = I_c/E. At an R₀ of 4, the I_c is 75% and at an E of 90%, more than 80% of a population need to be vaccinated to establish herd immunity. Such vaccination rates are currently unrealistic because of resistance against vaccinations, financial/logistical challenges, and a lack of vaccines that provide long-term protection against all human-pathogenic Ebolaviruses. Hence, outbreak management will for the foreseeable future depend on surveillance and case isolation. Clinical vaccine candidates are only available for Ebola viruses. Their use will need to be focused on health-care workers, potentially in combination with ring vaccination approaches.</p

Data_Sheet_1_Herd Immunity to Ebolaviruses Is Not a Realistic Target for Current Vaccination Strategies.xlsx

<p>The recent West African Ebola virus pandemic, which affected >28,000 individuals increased interest in anti-Ebolavirus vaccination programs. Here, we systematically analyzed the requirements for a prophylactic vaccination program based on the basic reproductive number (R₀, i.e., the number of secondary cases that result from an individual infection). Published R₀ values were determined by systematic literature research and ranged from 0.37 to 20. R₀s ≥ 4 realistically reflected the critical early outbreak phases and superspreading events. Based on the R₀, the herd immunity threshold (I_c) was calculated using the equation I_c = 1 − (1/R₀). The critical vaccination coverage (V_c) needed to provide herd immunity was determined by including the vaccine effectiveness (E) using the equation V_c = I_c/E. At an R₀ of 4, the I_c is 75% and at an E of 90%, more than 80% of a population need to be vaccinated to establish herd immunity. Such vaccination rates are currently unrealistic because of resistance against vaccinations, financial/logistical challenges, and a lack of vaccines that provide long-term protection against all human-pathogenic Ebolaviruses. Hence, outbreak management will for the foreseeable future depend on surveillance and case isolation. Clinical vaccine candidates are only available for Ebola viruses. Their use will need to be focused on health-care workers, potentially in combination with ring vaccination approaches.</p

Additional file 1: of Investigating Ebola virus pathogenicity using molecular dynamics

contains Figures. S1-S4. Legends for each of the figures are provided below: Figure S1. RMSD curves for VP24 KPNA5 complex trajectories. A) Ebola (black line) and Reston (red line) in complex with KPNA5 are shown. The Reston complex showed a higher RMSD that could be explained with the suboptimal binding between the two monomers (red line), while the EBOV complex showed a lower RMSD during the whole 600 ns trajectory, meaning a greater stability of the complex. B) For Ebola VP24 in complex with KPNA5 for wild type and the set of mutated Ebola VP24 proteins. Figure S2. DSSP graphs for the two wild type complexes. On the left side of the graph, the evolution of the EBOV secondary structure is shown in EBOV VP24 (on the top) and KPNA5 (on the bottom). On the right side, the evolution of the RESTV secondary structure is shown for RESTV VP24 (on the top of the graph) and KPNA5 (on the bottom). Residues at the interfaces are mapped in yellow circles. Figure S3. Local error of structural alphabet fit. The RMSD distribution per fragment position was calculated for a) WT EBOV VP24 and KPNA5, b) R137A EBOV VP24 and KPNA5 and c) RESTV VP24 and KPNA5. Figure S4. Hydrogen bonding in the Ebola and Reston virus VP24 complexes with KPNA5. Probability distribution of the number of H-bonds at the interface during the simulation for Ebola virus VP24- KPNA5 complex (black) and for Reston virus VP24- KPNA5 (red). (PDF 1132 kb

Data_Sheet_3_Herd Immunity to Ebolaviruses Is Not a Realistic Target for Current Vaccination Strategies.PDF

<p>The recent West African Ebola virus pandemic, which affected >28,000 individuals increased interest in anti-Ebolavirus vaccination programs. Here, we systematically analyzed the requirements for a prophylactic vaccination program based on the basic reproductive number (R₀, i.e., the number of secondary cases that result from an individual infection). Published R₀ values were determined by systematic literature research and ranged from 0.37 to 20. R₀s ≥ 4 realistically reflected the critical early outbreak phases and superspreading events. Based on the R₀, the herd immunity threshold (I_c) was calculated using the equation I_c = 1 − (1/R₀). The critical vaccination coverage (V_c) needed to provide herd immunity was determined by including the vaccine effectiveness (E) using the equation V_c = I_c/E. At an R₀ of 4, the I_c is 75% and at an E of 90%, more than 80% of a population need to be vaccinated to establish herd immunity. Such vaccination rates are currently unrealistic because of resistance against vaccinations, financial/logistical challenges, and a lack of vaccines that provide long-term protection against all human-pathogenic Ebolaviruses. Hence, outbreak management will for the foreseeable future depend on surveillance and case isolation. Clinical vaccine candidates are only available for Ebola viruses. Their use will need to be focused on health-care workers, potentially in combination with ring vaccination approaches.</p

Data_Sheet_5_Herd Immunity to Ebolaviruses Is Not a Realistic Target for Current Vaccination Strategies.PDF

<p>The recent West African Ebola virus pandemic, which affected >28,000 individuals increased interest in anti-Ebolavirus vaccination programs. Here, we systematically analyzed the requirements for a prophylactic vaccination program based on the basic reproductive number (R₀, i.e., the number of secondary cases that result from an individual infection). Published R₀ values were determined by systematic literature research and ranged from 0.37 to 20. R₀s ≥ 4 realistically reflected the critical early outbreak phases and superspreading events. Based on the R₀, the herd immunity threshold (I_c) was calculated using the equation I_c = 1 − (1/R₀). The critical vaccination coverage (V_c) needed to provide herd immunity was determined by including the vaccine effectiveness (E) using the equation V_c = I_c/E. At an R₀ of 4, the I_c is 75% and at an E of 90%, more than 80% of a population need to be vaccinated to establish herd immunity. Such vaccination rates are currently unrealistic because of resistance against vaccinations, financial/logistical challenges, and a lack of vaccines that provide long-term protection against all human-pathogenic Ebolaviruses. Hence, outbreak management will for the foreseeable future depend on surveillance and case isolation. Clinical vaccine candidates are only available for Ebola viruses. Their use will need to be focused on health-care workers, potentially in combination with ring vaccination approaches.</p

Additional file 2: Figure S2. of Checkpoint kinase inhibitor AZD7762 strongly sensitises urothelial carcinoma cells to gemcitabine

Viability in UCCs after combined treatments with cisplatin, romidepsin or givinostat, and AZD7762. a Relative cell viability in the T24 and RT-112 cell lines was measured by MTT assay (mean ± SD, n = 4) after cells were treated for 48 h either with cisplatin, romidepsin or givinostat combined with AZD7762. b Western blot analysis of S345 CHK1 after treatments with gemcitabine (10 nM), cisplatin (5 μM), romidepsin (4 nM) and givinostat (0.5 μM) in T24 cells (24 and 48 h). As loading control, GAPDH was stained. (TIF 214 kb

MOESM1 of Sprifermin (rhFGF18) modulates extracellular matrix turnover in cartilage explants ex vivo

Additional file 1. Aggrecan formation in bovine cartilage explants. Bovine cartilage explants were pre-cultured for 1 week, and then cultured for further 5 weeks with weekly administration (48 h duration) of indicated compounds. CS846 (IBEX Pharmaceuticals Inc.) was measured in conditioned media collected at 1, 3 and 5 weeks of compound-culturing. Values were placebo-corrected and all data presented as means ¹ SEM of six replicate explants. One-way ANOVA was used for multiple comparisons to the placebo group at each time point. Significance levels are indicated by asterisks; *P < 0.05, **P < 0.01, ***P < 0.001. All results are from one study (Study 2)

Additional file 3: Figure S3. of Checkpoint kinase inhibitor AZD7762 strongly sensitises urothelial carcinoma cells to gemcitabine

a, b Immunofluorescence staining of γH2A.X (green), 53-BP1 (red), and nuclei staining with DAPI (blue) in VM-CUB1 (a) and RT-112 (b) cells after the indicated treatments. Scale bar = 50 μm. (TIF 1728 kb

Additional file 1: Figure S1. of Checkpoint kinase inhibitor AZD7762 strongly sensitises urothelial carcinoma cells to gemcitabine

Viability in UCCs after sequential treatment with AZD7762 and gemcitabine. Relative cell viability in several UCCs was measured by MTT assay (mean ± SD, n = 4) after cells were sequentially treated (pretreated with AZD7762 for 24 h and then incubated with gemcitabine for 48 h). (TIF 142 kb