Ebolavirus Glycoprotein Fc Fusion Protein Protects Guinea Pigs against Lethal Challenge

Konduru, Krishnamurthy; Shurtleff, Amy C.; Bradfute, Steven B.; Nakamura, Siham; Bavari, Sina; Kaplan, Gerardo; Tsuji, Moriya

doi:10.1371/journal.pone.0162446

Ebolavirus Glycoprotein Fc Fusion Protein Protects Guinea Pigs against Lethal Challenge

Journal Article · Tue Sep 13 00:00:00 EDT 2016 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0162446· OSTI ID:1377872

Konduru, Krishnamurthy ^[1]; Shurtleff, Amy C. ^[2]; Bradfute, Steven B. ^[3]; Nakamura, Siham ^[1]; Bavari, Sina ^[2]; Kaplan, Gerardo ^[1]; Tsuji, Moriya ^[4]

Food and Drug Administration, Silver Spring, MD (United States)
United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD (United States)
United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD (United States); Univ. of New Mexico, Albuquerque, NM (United States)
Rockefeller Univ., New York, NY (United States)

Ebola virus (EBOV), a member of the Filoviridae that can cause severe hemorrhagic fever in humans and nonhuman primates, poses a significant threat to the public health. Currently, there are no licensed vaccines or therapeutics to prevent and treat EBOV infection. Several vaccines based on the EBOV glycoprotein (GP) are under development, including vectored, virus-like particles, and protein-based subunit vaccines. We previously demonstrated that a subunit vaccine containing the extracellular domain of the Ebola ebolavirus (EBOV) GP fused to the Fc fragment of human IgG1 (EBOVgp-Fc) protected mice against EBOV lethal challenge. Here, we show that the EBOVgp-Fc vaccine formulated with QS-21, alum, or polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) adjuvants induced strong humoral immune responses in guinea pigs. The vaccinated animals developed anti-GP total antibody titers of approximately 10⁵–10⁶ and neutralizing antibody titers of approximately 10³ as assessed by a BSL-2 neutralization assay based on vesicular stomatitis virus (VSV) pseudotypes. The poly-ICLC formulated EBOVgp-Fc vaccine protected all the guinea pigs against EBOV lethal challenge performed under BSL-4 conditions whereas the same vaccine formulated with QS-21 or alum only induced partial protection. Vaccination with a mucin-deletedEBOVgp-Fc construct formulated with QS-21 adjuvant did not have a significant effect in anti-GP antibody levels and protection against EBOV lethal challenge compared to the full-lengthGP construct. The bulk of the humoral response induced by the EBOVgp-Fc vaccine was directed against epitopes outside the EBOV mucin region. Our findings indicate that different adjuvants can eliciting varying levels of protection against lethal EBOV challenge in guinea pigs vaccinated with EBOVgp-Fc,and suggest that levels of total anti-GP antibodies elicit by protein-based GP subunit vaccines do not correlate with protection. In conclusion, our data further support the development of Fc fusions of GP as a candidate vaccine for human use.

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Research Organization:: Food and Drug Administration, Silver Spring, MD (United States)

Sponsoring Organization:: USDOE

OSTI ID:: 1377872

Journal Information:: PLoS ONE, Journal Name: PLoS ONE Journal Issue: 9 Vol. 11; ISSN 1932-6203

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
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antibodies
enzyme-linked immunoassays
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immunologic adjuvants
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vesicular stomatitis virus

Ebolavirus Glycoprotein Fc Fusion Protein Protects Guinea Pigs against Lethal Challenge

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