PMID- 26109675 OWN - NLM STAT- MEDLINE DCOM- 20151201 LR - 20181113 IS - 1537-6613 (Electronic) IS - 0022-1899 (Print) IS - 0022-1899 (Linking) VI - 212 Suppl 2 IP - Suppl 2 DP - 2015 Oct 1 TI - Vaccination With a Highly Attenuated Recombinant Vesicular Stomatitis Virus Vector Protects Against Challenge With a Lethal Dose of Ebola Virus. PG - S443-51 LID - 10.1093/infdis/jiv316 [doi] AB - Previously, recombinant vesicular stomatitis virus (rVSV) pseudotypes expressing Ebolavirus glycoproteins (GPs) in place of the VSV G protein demonstrated protection of nonhuman primates from lethal homologous Ebolavirus challenge. Those pseudotype vectors contained no additional attenuating mutations in the rVSV genome. Here we describe rVSV vectors containing a full complement of VSV genes and expressing the Ebola virus (EBOV) GP from an additional transcription unit. These rVSV vectors contain the same combination of attenuating mutations used previously in the clinical development pathway of an rVSV/human immunodeficiency virus type 1 vaccine. One of these rVSV vectors (N4CT1-EBOVGP1), which expresses membrane-anchored EBOV GP from the first position in the genome (GP1), elicited a balanced cellular and humoral GP-specific immune response in mice. Guinea pigs immunized with a single dose of this vector were protected from any signs of disease following lethal EBOV challenge, while control animals died in 7-9 days. Subsequently, N4CT1-EBOVGP1 demonstrated complete, single-dose protection of 2 macaques following lethal EBOV challenge. A single sham-vaccinated macaque died from disease due to EBOV infection. These results demonstrate that highly attenuated rVSV vectors expressing EBOV GP may provide safer alternatives to current EBOV vaccines. CI - (c) The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. FAU - Matassov, Demetrius AU - Matassov D AD - Department of Virology and Vaccine Vectors. FAU - Marzi, Andrea AU - Marzi A AD - Laboratory of Virology. FAU - Latham, Terri AU - Latham T AD - Department of Virology and Vaccine Vectors. FAU - Xu, Rong AU - Xu R AD - Department of Immunology, Profectus BioSciences, Tarrytown, New York. FAU - Ota-Setlik, Ayuko AU - Ota-Setlik A AD - Department of Immunology, Profectus BioSciences, Tarrytown, New York. FAU - Feldmann, Friederike AU - Feldmann F AD - Rocky Mountain Veterinary Branch, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana. FAU - Geisbert, Joan B AU - Geisbert JB AD - Galveston National Laboratory Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston. FAU - Mire, Chad E AU - Mire CE AD - Galveston National Laboratory Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston. FAU - Hamm, Stefan AU - Hamm S AD - Department of Virology and Vaccine Vectors. FAU - Nowak, Becky AU - Nowak B AD - Department of Virology and Vaccine Vectors. FAU - Egan, Michael A AU - Egan MA AD - Department of Immunology, Profectus BioSciences, Tarrytown, New York. FAU - Geisbert, Thomas W AU - Geisbert TW AD - Galveston National Laboratory Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston. FAU - Eldridge, John H AU - Eldridge JH AD - Department of Virology and Vaccine Vectors Department of Immunology, Profectus BioSciences, Tarrytown, New York. FAU - Feldmann, Heinz AU - Feldmann H AD - Laboratory of Virology. FAU - Clarke, David K AU - Clarke DK AD - Department of Virology and Vaccine Vectors. LA - eng GR - R01 AI098817/AI/NIAID NIH HHS/United States GR - U19 AI109711/AI/NIAID NIH HHS/United States GR - Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural DEP - 20150624 PL - United States TA - J Infect Dis JT - The Journal of infectious diseases JID - 0413675 RN - 0 (Antibodies, Viral) RN - 0 (Glycoproteins) RN - 0 (Vaccines, Attenuated) RN - 0 (Viral Proteins) RN - 0 (Viral Vaccines) SB - IM MH - Animals MH - Antibodies, Viral/immunology MH - Ebolavirus/*immunology MH - Female MH - Genetic Vectors/genetics/*immunology MH - Glycoproteins/genetics/immunology MH - Guinea Pigs MH - Hemorrhagic Fever, Ebola/*immunology/virology MH - Immunity, Cellular/immunology MH - Immunity, Humoral/immunology MH - Macaca mulatta MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Vaccination/methods MH - Vaccines, Attenuated/*immunology MH - Vesicular Stomatitis/immunology MH - Vesiculovirus/immunology MH - Viral Proteins/immunology MH - Viral Vaccines/*immunology PMC - PMC4564554 OTO - NOTNLM OT - Ebola vaccine OT - attenuation OT - challenge OT - glycoprotein OT - nonhuman primates OT - rVSV vector EDAT- 2015/06/26 06:00 MHDA- 2015/12/15 06:00 PMCR- 2015/09/01 CRDT- 2015/06/26 06:00 PHST- 2015/06/26 06:00 [entrez] PHST- 2015/06/26 06:00 [pubmed] PHST- 2015/12/15 06:00 [medline] PHST- 2015/09/01 00:00 [pmc-release] AID - jiv316 [pii] AID - 10.1093/infdis/jiv316 [doi] PST - ppublish SO - J Infect Dis. 2015 Oct 1;212 Suppl 2(Suppl 2):S443-51. doi: 10.1093/infdis/jiv316. Epub 2015 Jun 24.