A replication defective recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adults

J. E. Ledgerwood; P. Costner; N. Desai; L. Holman; M. E. Enama; G. Yamshchikov; S. Mulangu; Z. Hu; C. A. Andrews; R. A. Sheets; R. A. Koup; M. Roederer; R. Bailer; J. R. Mascola; M. G. Pau; N. J. Sullivan; J. Goudsmit; G. J. Nabel; B. S. Graham

doi:10.1016/j.vaccine.2010.10.037

A replication defective recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adults

J. E. Ledgerwood, P. Costner, N. Desai, L. Holman, M. E. Enama, G. Yamshchikov, S. Mulangu, Z. Hu, C. A. Andrews, R. A. Sheets, R. A. Koup, M. Roederer, R. Bailer, J. R. Mascola, M. G. Pau, N. J. Sullivan, J. Goudsmit, G. J. Nabel, B. S. Graham

Research output: Contribution to journal › Article › peer-review

156 Scopus citations

Abstract

Ebola virus causes irregular outbreaks of severe hemorrhagic fever in equatorial Africa. Case mortality remains high; there is no effective treatment and outbreaks are sporadic and unpredictable. Studies of Ebola virus vaccine platforms in non-human primates have established that the induction of protective immunity is possible and safety and human immunogenicity has been demonstrated in a previous Phase I clinical trial of a 1st generation Ebola DNA vaccine. We now report the safety and immunogenicity of a recombinant adenovirus serotype 5 (rAd5) vaccine encoding the envelope glycoprotein (GP) from the Zaire and Sudan Ebola virus species, in a randomized, placebo-controlled, double-blinded, dose escalation, Phase I human study. Thirty-one healthy adults received vaccine at 2×10⁹ (n=12), or 2×10¹⁰ (n=11) viral particles or placebo (n=8) as an intramuscular injection. Antibody responses were assessed by ELISA and neutralizing assays; and T cell responses were assessed by ELISpot and intracellular cytokine staining assays. This recombinant Ebola virus vaccine was safe and subjects developed antigen specific humoral and cellular immune responses.

Original language	English (US)
Pages (from-to)	304-313
Number of pages	10
Journal	Vaccine
Volume	29
Issue number	2
DOIs	https://doi.org/10.1016/j.vaccine.2010.10.037
State	Published - Dec 16 2010
Externally published	Yes

Keywords

Adenovirus
Ebola
Filovirus vaccine
Gene-based vaccines

ASJC Scopus subject areas

Immunology and Microbiology(all)
Infectious Diseases
Public Health, Environmental and Occupational Health
veterinary(all)
Molecular Medicine

Access to Document

10.1016/j.vaccine.2010.10.037

Cite this

Ledgerwood, J. E., Costner, P., Desai, N., Holman, L., Enama, M. E., Yamshchikov, G., Mulangu, S., Hu, Z., Andrews, C. A., Sheets, R. A., Koup, R. A., Roederer, M., Bailer, R., Mascola, J. R., Pau, M. G., Sullivan, N. J., Goudsmit, J., Nabel, G. J., & Graham, B. S. (2010). A replication defective recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adults. Vaccine, 29(2), 304-313. https://doi.org/10.1016/j.vaccine.2010.10.037

Ledgerwood, JE, Costner, P, Desai, N, Holman, L, Enama, ME, Yamshchikov, G, Mulangu, S, Hu, Z, Andrews, CA, Sheets, RA, Koup, RA, Roederer, M, Bailer, R, Mascola, JR, Pau, MG, Sullivan, NJ, Goudsmit, J, Nabel, GJ & Graham, BS 2010, 'A replication defective recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adults', Vaccine, vol. 29, no. 2, pp. 304-313. https://doi.org/10.1016/j.vaccine.2010.10.037

@article{c2a306f087ea48ada875058ec0facb24,

title = "A replication defective recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adults",

abstract = "Ebola virus causes irregular outbreaks of severe hemorrhagic fever in equatorial Africa. Case mortality remains high; there is no effective treatment and outbreaks are sporadic and unpredictable. Studies of Ebola virus vaccine platforms in non-human primates have established that the induction of protective immunity is possible and safety and human immunogenicity has been demonstrated in a previous Phase I clinical trial of a 1st generation Ebola DNA vaccine. We now report the safety and immunogenicity of a recombinant adenovirus serotype 5 (rAd5) vaccine encoding the envelope glycoprotein (GP) from the Zaire and Sudan Ebola virus species, in a randomized, placebo-controlled, double-blinded, dose escalation, Phase I human study. Thirty-one healthy adults received vaccine at 2×109 (n=12), or 2×1010 (n=11) viral particles or placebo (n=8) as an intramuscular injection. Antibody responses were assessed by ELISA and neutralizing assays; and T cell responses were assessed by ELISpot and intracellular cytokine staining assays. This recombinant Ebola virus vaccine was safe and subjects developed antigen specific humoral and cellular immune responses.",

keywords = "Adenovirus, Ebola, Filovirus vaccine, Gene-based vaccines",

author = "Ledgerwood, {J. E.} and P. Costner and N. Desai and L. Holman and Enama, {M. E.} and G. Yamshchikov and S. Mulangu and Z. Hu and Andrews, {C. A.} and Sheets, {R. A.} and Koup, {R. A.} and M. Roederer and R. Bailer and Mascola, {J. R.} and Pau, {M. G.} and Sullivan, {N. J.} and J. Goudsmit and Nabel, {G. J.} and Graham, {B. S.}",

year = "2010",

month = dec,

day = "16",

doi = "10.1016/j.vaccine.2010.10.037",

language = "English (US)",

volume = "29",

pages = "304--313",

journal = "Vaccine",

issn = "0264-410X",

publisher = "Elsevier BV",

number = "2",

}

TY - JOUR

T1 - A replication defective recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adults

AU - Ledgerwood, J. E.

AU - Costner, P.

AU - Desai, N.

AU - Holman, L.

AU - Enama, M. E.

AU - Yamshchikov, G.

AU - Mulangu, S.

AU - Hu, Z.

AU - Andrews, C. A.

AU - Sheets, R. A.

AU - Koup, R. A.

AU - Roederer, M.

AU - Bailer, R.

AU - Mascola, J. R.

AU - Pau, M. G.

AU - Sullivan, N. J.

AU - Goudsmit, J.

AU - Nabel, G. J.

AU - Graham, B. S.

PY - 2010/12/16

Y1 - 2010/12/16

N2 - Ebola virus causes irregular outbreaks of severe hemorrhagic fever in equatorial Africa. Case mortality remains high; there is no effective treatment and outbreaks are sporadic and unpredictable. Studies of Ebola virus vaccine platforms in non-human primates have established that the induction of protective immunity is possible and safety and human immunogenicity has been demonstrated in a previous Phase I clinical trial of a 1st generation Ebola DNA vaccine. We now report the safety and immunogenicity of a recombinant adenovirus serotype 5 (rAd5) vaccine encoding the envelope glycoprotein (GP) from the Zaire and Sudan Ebola virus species, in a randomized, placebo-controlled, double-blinded, dose escalation, Phase I human study. Thirty-one healthy adults received vaccine at 2×109 (n=12), or 2×1010 (n=11) viral particles or placebo (n=8) as an intramuscular injection. Antibody responses were assessed by ELISA and neutralizing assays; and T cell responses were assessed by ELISpot and intracellular cytokine staining assays. This recombinant Ebola virus vaccine was safe and subjects developed antigen specific humoral and cellular immune responses.

AB - Ebola virus causes irregular outbreaks of severe hemorrhagic fever in equatorial Africa. Case mortality remains high; there is no effective treatment and outbreaks are sporadic and unpredictable. Studies of Ebola virus vaccine platforms in non-human primates have established that the induction of protective immunity is possible and safety and human immunogenicity has been demonstrated in a previous Phase I clinical trial of a 1st generation Ebola DNA vaccine. We now report the safety and immunogenicity of a recombinant adenovirus serotype 5 (rAd5) vaccine encoding the envelope glycoprotein (GP) from the Zaire and Sudan Ebola virus species, in a randomized, placebo-controlled, double-blinded, dose escalation, Phase I human study. Thirty-one healthy adults received vaccine at 2×109 (n=12), or 2×1010 (n=11) viral particles or placebo (n=8) as an intramuscular injection. Antibody responses were assessed by ELISA and neutralizing assays; and T cell responses were assessed by ELISpot and intracellular cytokine staining assays. This recombinant Ebola virus vaccine was safe and subjects developed antigen specific humoral and cellular immune responses.

KW - Adenovirus

KW - Ebola

KW - Filovirus vaccine

KW - Gene-based vaccines

UR - http://www.scopus.com/inward/record.url?scp=78649703575&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78649703575&partnerID=8YFLogxK

U2 - 10.1016/j.vaccine.2010.10.037

DO - 10.1016/j.vaccine.2010.10.037

M3 - Article

C2 - 21034824

AN - SCOPUS:78649703575

SN - 0264-410X

VL - 29

SP - 304

EP - 313

JO - Vaccine

JF - Vaccine

IS - 2

ER -

A replication defective recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adults

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this