BACKGROUND: In humans and nonhuman primates, Ebola virus causes a virulent viral hemorrhagic fever for which no licensed vaccines or therapeutic drugs exist. In the present study, we used the mouse model for Ebola hemorrhagic fever to assess the safety and efficacy of a vaccine based on a live attenuated vesicular stomatitis virus expressing the Zaire ebolavirus (ZEBOV) glycoprotein. METHODS: Healthy mice were given the vaccine in various doses, decreasing from 2 x 10(4) to 2 plaque-forming units (pfu), with both systemic and mucosal vaccination routes used. Mice were challenged with 10(3) to 10(6) lethal doses of mouse-adapted ZEBOV. Severely immunocompromised mice were injected with 2 x 10(5) pfu, which is 10 times greater than the immunization dose normally used, to test vaccine safety. RESULTS: Two plaque-forming units of the vaccine protected against lethal challenge, and mucosal immunization was found to be as protective as systemic injection. The replicating vaccine was never detected in the immunized animals, nor were there clinical signs after immunization. Immunization of severely immunocompromised mice with 200,000 pfu of vaccine resulted in no clinical symptoms. CONCLUSIONS: Our data suggest that the vaccine is highly potent and safe and that it very rapidly induces "sterile" immunity in mice. The potential for mucosal delivery, if confirmed in nonhuman primates, makes it an excellent candidate for mass immunization during outbreaks or in the event of intentional release.
BACKGROUND: In humans and nonhuman primates, Ebola virus causes a virulent viral hemorrhagic fever for which no licensed vaccines or therapeutic drugs exist. In the present study, we used the mouse model for Ebola hemorrhagic fever to assess the safety and efficacy of a vaccine based on a live attenuated vesicular stomatitis virus expressing the Zaire ebolavirus (ZEBOV) glycoprotein. METHODS: Healthy mice were given the vaccine in various doses, decreasing from 2 x 10(4) to 2 plaque-forming units (pfu), with both systemic and mucosal vaccination routes used. Mice were challenged with 10(3) to 10(6) lethal doses of mouse-adapted ZEBOV. Severely immunocompromised mice were injected with 2 x 10(5) pfu, which is 10 times greater than the immunization dose normally used, to test vaccine safety. RESULTS: Two plaque-forming units of the vaccine protected against lethal challenge, and mucosal immunization was found to be as protective as systemic injection. The replicating vaccine was never detected in the immunized animals, nor were there clinical signs after immunization. Immunization of severely immunocompromised mice with 200,000 pfu of vaccine resulted in no clinical symptoms. CONCLUSIONS: Our data suggest that the vaccine is highly potent and safe and that it very rapidly induces "sterile" immunity in mice. The potential for mucosal delivery, if confirmed in nonhuman primates, makes it an excellent candidate for mass immunization during outbreaks or in the event of intentional release.
Authors: Selidji T Agnandji; Angela Huttner; Madeleine E Zinser; Patricia Njuguna; Christine Dahlke; José F Fernandes; Sabine Yerly; Julie-Anne Dayer; Verena Kraehling; Rahel Kasonta; Akim A Adegnika; Marcus Altfeld; Floriane Auderset; Emmanuel B Bache; Nadine Biedenkopf; Saskia Borregaard; Jessica S Brosnahan; Rebekah Burrow; Christophe Combescure; Jules Desmeules; Markus Eickmann; Sarah K Fehling; Axel Finckh; Ana Rita Goncalves; Martin P Grobusch; Jay Hooper; Alen Jambrecina; Anita L Kabwende; Gürkan Kaya; Domtila Kimani; Bertrand Lell; Barbara Lemaître; Ansgar W Lohse; Marguerite Massinga-Loembe; Alain Matthey; Benjamin Mordmüller; Anne Nolting; Caroline Ogwang; Michael Ramharter; Jonas Schmidt-Chanasit; Stefan Schmiedel; Peter Silvera; Felix R Stahl; Henry M Staines; Thomas Strecker; Hans C Stubbe; Benjamin Tsofa; Sherif Zaki; Patricia Fast; Vasee Moorthy; Laurent Kaiser; Sanjeev Krishna; Stephan Becker; Marie-Paule Kieny; Philip Bejon; Peter G Kremsner; Marylyn M Addo; Claire-Anne Siegrist Journal: N Engl J Med Date: 2015-04-01 Impact factor: 91.245
Authors: Nicholas J Lennemann; Andrew S Herbert; Rachel Brouillette; Bethany Rhein; Russell A Bakken; Katherine J Perschbacher; Ashley L Cooney; Catherine L Miller-Hunt; Patrick Ten Eyck; Julia Biggins; Gene Olinger; John M Dye; Wendy Maury Journal: J Virol Date: 2017-08-10 Impact factor: 5.103