Characterization of Immune Responses Induced by Ebola Virus Glycoprotein (GP) and Truncated GP Isoform DNA Vaccines and Protection Against Lethal Ebola Virus Challenge in Mice

In addition to its surface glycoprotein (GP), Ebola virus directs the production of large quantities of a truncated glycoprotein isoform (sGP) that is secreted into the extracellular space. We recently reported that sGP actively diverts host antibody responses against the epitopes that it shares wit...

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Bibliographic Details
Published in:The Journal of infectious diseases Vol. 212 Suppl 2; p. S398
Main Authors: Li, Wenfang, Ye, Ling, Carrion, Jr, Ricardo, Mohan, Gopi S, Nunneley, Jerritt, Staples, Hilary, Ticer, Anysha, Patterson, Jean L, Compans, Richard W, Yang, Chinglai
Format: Journal Article
Language:English
Published: United States 01.10.2015
Subjects:
Animals
Antibodies, Viral - immunology
Antibody Formation - immunology
Ebola Vaccines - immunology
Ebolavirus - immunology
Female
Glycoproteins - immunology
HEK293 Cells
Hemorrhagic Fever, Ebola - immunology
Hemorrhagic Fever, Ebola - virology
Humans
Immunization, Secondary - methods
Mice
Mice, Inbred BALB C
Protein Isoforms - immunology
Vaccination - methods
Vaccines, DNA - immunology
Viral Proteins - immunology
antigenic subversion
vaccine
Ebola
soluble GP
ISSN:1537-6613, 1537-6613
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Summary:In addition to its surface glycoprotein (GP), Ebola virus directs the production of large quantities of a truncated glycoprotein isoform (sGP) that is secreted into the extracellular space. We recently reported that sGP actively diverts host antibody responses against the epitopes that it shares with GP and thereby allows itself to absorb anti-GP antibodies, a phenomenon we termed "antigenic subversion." To investigate the effect of antigenic subversion by sGP on protection against virus infection, we compared immune responses induced by different prime-boost immunization regimens with GP and sGP DNA vaccines in mice and their efficacy against lethal Ebola virus challenge. Similar levels of anti-GP antibodies were induced by 2 immunizations with sGP and GP DNA vaccines. However, 2 immunizations with GP but not sGP DNA vaccine fully protected mice from lethal challenge. Boosting with sGP or GP DNA vaccine in mice that had been primed by GP or sGP DNA vaccine augmented the levels of anti-GP antibody responses and further improved protective efficacy against Ebola virus infection. These results show that both the quality and the levels of anti-GP antibody responses affect the efficacy of protection against Ebola virus infection.
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ISSN:1537-6613
1537-6613
DOI:10.1093/infdis/jiv186