Search

Your search keyword '"Catherine V. Badger"' showing total 2 results
Start Over Author "Catherine V. Badger" Publisher public library of science (plos)
2 results on '"Catherine V. Badger"'

1. A fusion-inhibiting peptide against Rift Valley fever virus inhibits multiple, diverse viruses.

Author

Jeffrey W Koehler, Jeffrey M Smith, Daniel R Ripoll, Kristin W Spik, Shannon L Taylor, Catherine V Badger, Rebecca J Grant, Monica M Ogg, Anders Wallqvist, Mary C Guttieri, Robert F Garry, and Connie S Schmaljohn

Subjects
Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract

For enveloped viruses, fusion of the viral envelope with a cellular membrane is critical for a productive infection to occur. This fusion process is mediated by at least three classes of fusion proteins (Class I, II, and III) based on the protein sequence and structure. For Rift Valley fever virus (RVFV), the glycoprotein Gc (Class II fusion protein) mediates this fusion event following entry into the endocytic pathway, allowing the viral genome access to the cell cytoplasm. Here, we show that peptides analogous to the RVFV Gc stem region inhibited RVFV infectivity in cell culture by inhibiting the fusion process. Further, we show that infectivity can be inhibited for diverse, unrelated RNA viruses that have Class I (Ebola virus), Class II (Andes virus), or Class III (vesicular stomatitis virus) fusion proteins using this single peptide. Our findings are consistent with an inhibition mechanism similar to that proposed for stem peptide fusion inhibitors of dengue virus in which the RVFV inhibitory peptide first binds to both the virion and cell membranes, allowing it to traffic with the virus into the endocytic pathway. Upon acidification and rearrangement of Gc, the peptide is then able to specifically bind to Gc and prevent fusion of the viral and endocytic membranes, thus inhibiting viral infection. These results could provide novel insights into conserved features among the three classes of viral fusion proteins and offer direction for the future development of broadly active fusion inhibitors.

Published
2013
Full Text
View/download PDF

2. A DNA vaccine for Crimean-Congo hemorrhagic fever protects against disease and death in two lethal mouse models

Author

Aura R. Garrison, Charles J. Shoemaker, Joseph W. Golden, Collin J. Fitzpatrick, John J. Suschak, Michelle J. Richards, Catherine V. Badger, Carolyn M. Six, Jacqueline D. Martin, Drew Hannaman, Marko Zivcec, Eric Bergeron, Jeffrey W. Koehler, and Connie S. Schmaljohn

Subjects
0301 basic medicine, Physiology, Antibody Response, Receptor, Interferon alpha-beta, DNA vaccination, Antibodies, Viral, Biochemistry, Mice, Immunogenicity, Vaccine, Immune Physiology, Medicine and Health Sciences, Vaccines, DNA, Enzyme-Linked Immunoassays, Immune Response, Mice, Knockout, Vaccines, Immune System Proteins, lcsh:Public aspects of medicine, Vaccination, Animal Models, Infectious Diseases, Experimental Organism Systems, Hemorrhagic Fever Virus, Crimean-Congo, Vaccination and immunization, Research Article, lcsh:Arctic medicine. Tropical medicine, Infectious Disease Control, lcsh:RC955-962, 030106 microbiology, Immunology, Mouse Models, Research and Analysis Methods, Antibodies, 03 medical and health sciences, Immunocompromised Host, Viral Proteins, Model Organisms, Th2 Cells, Animals, Humans, Immunoassays, Glycoproteins, Preventive medicine, Public Health, Environmental and Occupational Health, Biology and Life Sciences, Proteins, Viral Vaccines, lcsh:RA1-1270, Th1 Cells, Antibodies, Neutralizing, Immunity, Humoral, Disease Models, Animal, 030104 developmental biology, Public and occupational health, Immunologic Techniques, Hemorrhagic Fever, Crimean
Abstract

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus capable of causing a severe hemorrhagic fever disease in humans. There are currently no licensed vaccines to prevent CCHFV-associated disease. We developed a DNA vaccine expressing the M-segment glycoprotein precursor gene of CCHFV and assessed its immunogenicity and protective efficacy in two lethal mouse models of disease: type I interferon receptor knockout (IFNAR-/-) mice; and a novel transiently immune suppressed (IS) mouse model. Vaccination of mice by muscle electroporation of the M-segment DNA vaccine elicited strong antigen-specific humoral immune responses with neutralizing titers after three vaccinations in both IFNAR-/- and IS mouse models. To compare the protective efficacy of the vaccine in the two models, groups of vaccinated mice (7–10 per group) were intraperitoneally (IP) challenged with a lethal dose of CCHFV strain IbAr 10200. Weight loss was markedly reduced in CCHFV DNA-vaccinated mice as compared to controls. Furthermore, whereas all vector-control vaccinated mice succumbed to disease by day 5, the DNA vaccine protected >60% of the animals from lethal disease. Mice from both models developed comparable levels of antibodies, but the IS mice had a more balanced Th1/Th2 response to vaccination. There were no statistical differences in the protective efficacies of the vaccine in the two models. Our results provide the first comparison of these two mouse models for assessing a vaccine against CCHFV and offer supportive data indicating that a DNA vaccine expressing the glycoprotein genes of CCHFV elicits protective immunity against CCHFV., Author summary Crimean-Congo hemorrhagic Fever Virus (CCHFV) is a tick-borne virus capable of causing lethal human disease against which there are currently no approved vaccines. In this study, we compared the immunogenicity and protective efficacy of a candidate DNA vaccine expressing the glycoprotein precursor gene of CCHFV in two mouse models. In addition to the recently established IFNAR-/- mouse pathogenesis model, we also tested the vaccine in a novel murine system in which the interferon (IFN) α/β signaling response of immunocompetent mice is transiently suppressed. We found that the DNA vaccine elicited high humoral immune responses and provided significant protection against challenge with CCHFV in both mouse models. These findings further our understanding of the requirements for a CCHFV vaccine and provide a new mouse model for the development of CCHFV countermeasures.

Published
2017

Catalog

Books, media, physical & digital resources
See catalog results