TY - JOUR
T1 - A replicating single-cycle adenovirus vaccine against Ebola virus
AU - Anguiano-Zarate, Stephanie S.
AU - Matchett, William E.
AU - Nehete, Pramod N.
AU - Sastry, Jagannadha K.
AU - Marzi, Andrea
AU - Barry, Michael A.
N1 - Funding Information:
This work was supported by NIH/NIAID grants R01 AI096967 and R01 AI136718 and the Walter & Lucille Rubin Fund in Infectious Diseases Honoring Michael Camilleri, M.D. at Mayo Clinic, and the Discovery Translation Fund at Mayo Clinic (to M.A.B). This work was supported by the National Center for Advancing Translational Sciences (Clinical and Translational Science award UL1 TR000135 to S. S. A. Z.), National Institutes of Health; and by the Initiative for Maximizing Student Development (to S. S. A. Z.) at Mayo Clinic. This work was supported by the NIAID Intramural Research Fund (to A. M.).
Funding Information:
Financial support. This work was supported by NIH/NIAID grants R01 AI096967 and R01 AI136718 and the Walter & Lucille Rubin Fund in Infectious Diseases Honoring Michael Camilleri, M.D. at Mayo Clinic, and the Discovery Translation Fund at Mayo Clinic (to M.A.B). This work was supported by the National Center for Advancing Translational Sciences (Clinical and Translational Science award UL1 TR000135 to S. S. A. Z.), National Institutes of Health; and by the Initiative for Maximizing Student Development (to S. S. A. Z.) at Mayo Clinic. This work was supported by the NIAID Intramural Research Fund (to A. M.).
Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
PY - 2018/11/5
Y1 - 2018/11/5
N2 - Recent West African Ebola virus (EBOV) epidemics have led to testing different anti-EBOV vaccines, including a replication-defective adenovirus (RD-Ad) vector (ChAd3-EBOV) and an infectious, replication-competent recombinant vesicular stomatitis virus expressing the EBOV glycoprotein (rVSV-EBOV; also known as rVSV-ZEBOV). While RD-Ads elicit protection, when scaled up to human trials, the level of protection may be much lower than that of vaccines containing viruses that can replicate. Although a replication-competent Ad (RC-Ad) vaccine might generate a level of protection approximating that of rVSV, this infectious vector would also risk causing adenovirus disease. We recently described a “single-cycle” adenovirus (SC-Ad) vector that amplifies antigen genes like RC-Ad, but that avoids the risk of adenovirus infection. Here we have tested an SC-Ad6 vector expressing the glycoprotein (GP) from a 2014 EBOV strain in mice, hamsters, and rhesus macaques. We show that SC-Ad6-EBOV GP induces a high level of serum antibodies in all species and mediates significant protection against pseudo-challenge with rVSV-EBOV expressing luciferase in mice and hamsters. These data suggest that SC-Ad6-EBOV GP may be useful during future EBOV outbreaks.
AB - Recent West African Ebola virus (EBOV) epidemics have led to testing different anti-EBOV vaccines, including a replication-defective adenovirus (RD-Ad) vector (ChAd3-EBOV) and an infectious, replication-competent recombinant vesicular stomatitis virus expressing the EBOV glycoprotein (rVSV-EBOV; also known as rVSV-ZEBOV). While RD-Ads elicit protection, when scaled up to human trials, the level of protection may be much lower than that of vaccines containing viruses that can replicate. Although a replication-competent Ad (RC-Ad) vaccine might generate a level of protection approximating that of rVSV, this infectious vector would also risk causing adenovirus disease. We recently described a “single-cycle” adenovirus (SC-Ad) vector that amplifies antigen genes like RC-Ad, but that avoids the risk of adenovirus infection. Here we have tested an SC-Ad6 vector expressing the glycoprotein (GP) from a 2014 EBOV strain in mice, hamsters, and rhesus macaques. We show that SC-Ad6-EBOV GP induces a high level of serum antibodies in all species and mediates significant protection against pseudo-challenge with rVSV-EBOV expressing luciferase in mice and hamsters. These data suggest that SC-Ad6-EBOV GP may be useful during future EBOV outbreaks.
KW - Adenovirus
KW - Animal models
KW - Ebola virus
KW - Single cycle
KW - Vaccine
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U2 - 10.1093/infdis/jiy411
DO - 10.1093/infdis/jiy411
M3 - Article
C2 - 29982595
AN - SCOPUS:85056256238
SN - 0022-1899
VL - 218
SP - 1883
EP - 1889
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 12
ER -