CD8 + cellular immunity mediates rAd5 vaccine protection against Ebola virus infection of nonhuman primates

Nancy J. Sullivan, Lisa Hensley, Clement Asiedu, Thomas Geisbert, Daphne Stanley, Joshua Johnson, Anna Honko, Gene Olinger, Michael Bailey, Joan B. Geisbert, Keith A. Reimann, Saran Bao, Srinivas Rao, Mario Roederer, Peter B. Jahrling, Richard A. Koup, Gary J. Nabel

Research output: Contribution to journalArticle

138 Citations (Scopus)

Abstract

Vaccine-induced immunity to Ebola virus infection in nonhuman primates (NHPs) is marked by potent antigen-specific cellular and humoral immune responses; however, the immune mechanism of protection remains unknown. Here we define the immune basis of protection conferred by a highly protective recombinant adenovirus virus serotype 5 (rAd5) encoding Ebola virus glycoprotein (GP) in NHPs. Passive transfer of high-titer polyclonal antibodies from vaccinated Ebola virus-immune cynomolgus macaques to naive macaques failed to confer protection against disease, suggesting a limited role of humoral immunity. In contrast, depletion of CD3 + T cells in vivo after vaccination and immediately before challenge eliminated immunity in two vaccinated macaques, indicating a crucial requirement for T cells in this setting. The protective effect was mediated largely by CD8 + cells, as depletion of CD8 + cells in vivo using the cM-T807 monoclonal antibody (mAb), which does not affect CD4 + T cell or humoral immune responses, abrogated protection in four out of five subjects. These findings indicate that CD8 + cells have a major role in rAd5-GP-induced immune protection against Ebola virus infection in NHPs. Understanding the immunologic mechanism of Ebola virus protection will facilitate the development of vaccines for Ebola and related hemorrhagic fever viruses in humans.

Original languageEnglish (US)
Pages (from-to)1128-1131
Number of pages4
JournalNature Medicine
Volume17
Issue number9
DOIs
StatePublished - Sep 2011

Fingerprint

Ebola Hemorrhagic Fever
Ebolavirus
Macaca
Humoral Immunity
Viruses
Cellular Immunity
Primates
Vaccines
T-Lymphocytes
Immunity
Glycoproteins
T-cells
Adenoviridae
Vaccination
Ebola Vaccines
Monoclonal Antibodies
Antigens
Antibodies

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Sullivan, N. J., Hensley, L., Asiedu, C., Geisbert, T., Stanley, D., Johnson, J., ... Nabel, G. J. (2011). CD8 + cellular immunity mediates rAd5 vaccine protection against Ebola virus infection of nonhuman primates. Nature Medicine, 17(9), 1128-1131. https://doi.org/10.1038/nm.2447

CD8 + cellular immunity mediates rAd5 vaccine protection against Ebola virus infection of nonhuman primates. / Sullivan, Nancy J.; Hensley, Lisa; Asiedu, Clement; Geisbert, Thomas; Stanley, Daphne; Johnson, Joshua; Honko, Anna; Olinger, Gene; Bailey, Michael; Geisbert, Joan B.; Reimann, Keith A.; Bao, Saran; Rao, Srinivas; Roederer, Mario; Jahrling, Peter B.; Koup, Richard A.; Nabel, Gary J.

In: Nature Medicine, Vol. 17, No. 9, 09.2011, p. 1128-1131.

Research output: Contribution to journalArticle

Sullivan, NJ, Hensley, L, Asiedu, C, Geisbert, T, Stanley, D, Johnson, J, Honko, A, Olinger, G, Bailey, M, Geisbert, JB, Reimann, KA, Bao, S, Rao, S, Roederer, M, Jahrling, PB, Koup, RA & Nabel, GJ 2011, 'CD8 + cellular immunity mediates rAd5 vaccine protection against Ebola virus infection of nonhuman primates', Nature Medicine, vol. 17, no. 9, pp. 1128-1131. https://doi.org/10.1038/nm.2447
Sullivan, Nancy J. ; Hensley, Lisa ; Asiedu, Clement ; Geisbert, Thomas ; Stanley, Daphne ; Johnson, Joshua ; Honko, Anna ; Olinger, Gene ; Bailey, Michael ; Geisbert, Joan B. ; Reimann, Keith A. ; Bao, Saran ; Rao, Srinivas ; Roederer, Mario ; Jahrling, Peter B. ; Koup, Richard A. ; Nabel, Gary J. / CD8 + cellular immunity mediates rAd5 vaccine protection against Ebola virus infection of nonhuman primates. In: Nature Medicine. 2011 ; Vol. 17, No. 9. pp. 1128-1131.
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