47 research outputs found
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 (R<sub>0</sub>, i.e., the number of secondary cases that result from an individual infection). Published R<sub>0</sub> values were determined by systematic literature research and ranged from 0.37 to 20. R<sub>0</sub>s ≥ 4 realistically reflected the critical early outbreak phases and superspreading events. Based on the R<sub>0</sub>, the herd immunity threshold (I<sub>c</sub>) was calculated using the equation I<sub>c</sub> = 1 − (1/R<sub>0</sub>). The critical vaccination coverage (V<sub>c</sub>) needed to provide herd immunity was determined by including the vaccine effectiveness (E) using the equation V<sub>c</sub> = I<sub>c</sub>/E. At an R<sub>0</sub> of 4, the I<sub>c</sub> 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_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 (R<sub>0</sub>, i.e., the number of secondary cases that result from an individual infection). Published R<sub>0</sub> values were determined by systematic literature research and ranged from 0.37 to 20. R<sub>0</sub>s ≥ 4 realistically reflected the critical early outbreak phases and superspreading events. Based on the R<sub>0</sub>, the herd immunity threshold (I<sub>c</sub>) was calculated using the equation I<sub>c</sub> = 1 − (1/R<sub>0</sub>). The critical vaccination coverage (V<sub>c</sub>) needed to provide herd immunity was determined by including the vaccine effectiveness (E) using the equation V<sub>c</sub> = I<sub>c</sub>/E. At an R<sub>0</sub> of 4, the I<sub>c</sub> 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 (R<sub>0</sub>, i.e., the number of secondary cases that result from an individual infection). Published R<sub>0</sub> values were determined by systematic literature research and ranged from 0.37 to 20. R<sub>0</sub>s ≥ 4 realistically reflected the critical early outbreak phases and superspreading events. Based on the R<sub>0</sub>, the herd immunity threshold (I<sub>c</sub>) was calculated using the equation I<sub>c</sub> = 1 − (1/R<sub>0</sub>). The critical vaccination coverage (V<sub>c</sub>) needed to provide herd immunity was determined by including the vaccine effectiveness (E) using the equation V<sub>c</sub> = I<sub>c</sub>/E. At an R<sub>0</sub> of 4, the I<sub>c</sub> 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_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 (R<sub>0</sub>, i.e., the number of secondary cases that result from an individual infection). Published R<sub>0</sub> values were determined by systematic literature research and ranged from 0.37 to 20. R<sub>0</sub>s ≥ 4 realistically reflected the critical early outbreak phases and superspreading events. Based on the R<sub>0</sub>, the herd immunity threshold (I<sub>c</sub>) was calculated using the equation I<sub>c</sub> = 1 − (1/R<sub>0</sub>). The critical vaccination coverage (V<sub>c</sub>) needed to provide herd immunity was determined by including the vaccine effectiveness (E) using the equation V<sub>c</sub> = I<sub>c</sub>/E. At an R<sub>0</sub> of 4, the I<sub>c</sub> 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 (R<sub>0</sub>, i.e., the number of secondary cases that result from an individual infection). Published R<sub>0</sub> values were determined by systematic literature research and ranged from 0.37 to 20. R<sub>0</sub>s ≥ 4 realistically reflected the critical early outbreak phases and superspreading events. Based on the R<sub>0</sub>, the herd immunity threshold (I<sub>c</sub>) was calculated using the equation I<sub>c</sub> = 1 − (1/R<sub>0</sub>). The critical vaccination coverage (V<sub>c</sub>) needed to provide herd immunity was determined by including the vaccine effectiveness (E) using the equation V<sub>c</sub> = I<sub>c</sub>/E. At an R<sub>0</sub> of 4, the I<sub>c</sub> 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
A Novel Vaccine against Crimean-Congo Haemorrhagic Fever Protects 100% of Animals against Lethal Challenge in a Mouse Model
<div><p>Crimean-Congo Haemorrhagic Fever (CCHF) is a severe tick-borne disease, endemic in many countries in Africa, the Middle East, Eastern Europe and Asia. Between 15–70% of reported cases are fatal. There is no approved vaccine available, and preclinical protection <i>in vivo</i> by an experimental vaccine has not been demonstrated previously. In the present study, the attenuated poxvirus vector, Modified Vaccinia virus Ankara, was used to develop a recombinant candidate vaccine expressing the CCHF virus glycoproteins. Cellular and humoral immunogenicity was confirmed in two mouse strains, including type I interferon receptor knockout mice, which are susceptible to CCHF disease. This vaccine protected all recipient animals from lethal disease in a challenge model adapted to represent infection via a tick bite. Histopathology and viral load analysis of protected animals confirmed that they had been exposed to challenge virus, even though they did not exhibit clinical signs. This is the first demonstration of efficacy of a CCHF vaccine.</p></div
IFN-γ ELISpot responses from vaccinated A129 and 129Sv/Ev mice, 7 days after booster vaccination.
<p>Splenocytes from animals vaccinated with MVA-GP (orange), MVA 1974 or saline (black) were restimulated with peptides derived from the CCHFv glycoprotein. A129 mice data (solid bars) were pooled from 2 independent experiments (n = 8). 129Sv/Ev mice n = 5 (hatched bars). Mean ± SEM is plotted. (A) Summed antigen responses from all peptide pools. Splenocytes from MVA-GP vaccinated mice, but not control mice, responded to GP-specific peptides, indicating similar T-cell responses between mouse strains. (B) Antigen responses from MVA-GP vaccinated mice, according to peptide pool. Immunogenicity was not evenly distributed across the antigen, but some peptide pools were more immunogenic than others. Responses were specific to the glycoprotein, and similar between mouse strains.</p
Immunohistochemistry of tissues from A129 mice, 4 days after challenge with CCHFv.
<p>A129 mice were challenged with double the minimum lethal dose of CCHFv, 14 days after booster vaccination with MVA 1974 (A–C) or MVA-GP (D–E). Four days after challenge, sections of spleen (A, D) and liver (B–C, E) were fixed, immunohistochemically stained with CCHFv-specific antibody, and examined microscopically. Tissues in panels A, B, D and E were from the same individuals as shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0091516#pone-0091516-g007" target="_blank">Figures 7A, 7B, 7C and 7D</a>, respectively. A diffuse staining pattern of viral proteins was found in tissues from animals that received the MVA 1974 negative control. However, in MVA-GP vaccinated animals, the only staining found was of a minimal degree, in liver from one individual. (A) A few, scattered cells with cytoplasmic staining within the parenchyma. (B) Frequent, diffuse, positively stained hepatocytes. (C) Scattered, small, elongated cells consistent with Kupffer cells, with cytoplasmic staining. (D) Normal parenchyma. (E) A few, positively stained cells within an inflammatory cell focus.</p
Antibody responses from vaccinated A129 and 129Sv/Ev mice.
<p>Sera from vaccinated mice were tested for reactivity with CCHFv-infected (lane 3) or uninfected (lane 2) SW13 cells by Western blotting. Lane 1 shows a molecular weight marker. Blots show proteins reactive with serum from representative individual animals 7 days after booster vaccination (A–E) or representative pooled serum 14 days after booster vaccination (F). Secondary antibody used was specific for mouse IgG (A–C, F), or mouse IgG, IgA and IgM (D–E). Arrows highlight CCHFv-specific proteins, indicating specific antibody responses in both mouse strains. (A) 129Sv/Ev mouse vaccinated with MVA-GP. (B, D–E) A129 mouse vaccinated with MVA-GP. (C) A129 mouse vaccinated with MVA 1974. (F) Pooled sera from A129 mice vaccinated with MVA-GP.</p
Frequency of immunohistochemically stained cells in tissues from selected vaccinated A129 mice, challenged with CCHFv.
<p>Numbers of animals in each group, according to frequency of cells stained by immunohistochemistry.</p