Recombinant adenovirus serotype 26 (Ad26) and Ad35 vaccine vectors bypass immunity to ad5 and protect nonhuman primates against ebolavirus challenge

Thomas W. Geisbert, Michael Bailey, Lisa Hensley, Clement Asiedu, Joan Geisbert, Daphne Stanley, Anna Honko, Joshua Johnson, Sabue Mulangu, Maria Grazia Pau, Jerome Custers, Jort Vellinga, Jenny Hendriks, Peter Jahrling, Mario Roederer, Jaap Goudsmit, Richard Koup, Nancy J. Sullivan

Research output: Contribution to journalArticle

117 Scopus citations

Abstract

The use of adenoviruses (Ad) as vaccine vectors against a variety of pathogens has demonstrated their capacity to elicit strong antibody and cell-mediated immune responses. Adenovirus serotype C vectors, such as Ad serotype 5 (Ad5), expressing Ebolavirus (EBOV) glycoprotein (GP), protect completely after a single inoculation at a dose of 1010 viral particles. However, the clinical application of a vaccine based on Ad5 vectors may be hampered, since impairment of Ad5 vaccine efficacy has been demonstrated for humans and nonhuman primates with high levels of preexisting immunity to the vector. Ad26 and Ad35 segregate genetically from Ad5 and exhibit lower seroprevalence in humans, making them attractive vaccine vector alternatives. In the series of studies presented, we show that Ad26 and Ad35 vectors generate robust antigen-specific cell-mediated and humoral immune responses against EBOV GP and that Ad5 immune status does not affect the generation of GP-specific immune responses by these vaccines. We demonstrate partial protection against EBOV by a single-shot Ad26 vaccine and complete protection when this vaccine is boosted by Ad35 1 month later. Increases in efficacy are paralleled by substantial increases in T- and B-cell responses to EBOV GP. These results suggest that Ad26 and Ad35 vectors warrant further development as candidate vaccines for EBOV.

Original languageEnglish (US)
Pages (from-to)4222-4233
Number of pages12
JournalJournal of virology
Volume85
Issue number9
DOIs
StatePublished - May 2011

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Geisbert, T. W., Bailey, M., Hensley, L., Asiedu, C., Geisbert, J., Stanley, D., Honko, A., Johnson, J., Mulangu, S., Pau, M. G., Custers, J., Vellinga, J., Hendriks, J., Jahrling, P., Roederer, M., Goudsmit, J., Koup, R., & Sullivan, N. J. (2011). Recombinant adenovirus serotype 26 (Ad26) and Ad35 vaccine vectors bypass immunity to ad5 and protect nonhuman primates against ebolavirus challenge. Journal of virology, 85(9), 4222-4233. https://doi.org/10.1128/JVI.02407-10