Replicating single-cycle adenovirus vectors generate amplified influenza vaccine responses

Catherine M. Crosby, William E. Matchett, Stephanie S. Anguiano-Zarate, Christopher A. Parks, Eric A. Weaver, Larry R Pease, Richard J. Webby, Michael A Barry

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Head-to-head comparisons of conventional influenza vaccines with adenovirus (Ad) gene-based vaccines demonstrated that these viral vectors can mediate more potent protection against influenza virus infection in animal models. In most cases, Ad vaccines are engineered to be replication-defective (RD-Ad) vectors. In contrast, replication-competent Ad (RC-Ad) vaccines are markedly more potent but risk causing adenovirus diseases in vaccine recipients and health care workers. To harness antigen gene replication but avoid production of infectious virions, we developed "single-cycle" adenovirus (SC-Ad) vectors. Previous work demonstrated that SC-Ads amplify transgene expression 100-fold and produce markedly stronger and more persistent immune responses than RD-Ad vectors in Syrian hamsters and rhesus macaques. To test them as potential vaccines, we engineered RD and SC versions of adenovirus serotype 6 (Ad6) to express the hemagglutinin (HA) gene from influenza A/PR/8/34 virus. We show here that it takes approximately 33 times less SC-Ad6 than RD-Ad6 to produce equal amounts of HA antigen in vitro. SC-Ad produced markedly higher HA binding and hemagglutination inhibition (HAI) titers than RD-Ad in Syrian hamsters. SC-Ad-vaccinated cotton rats had markedly lower influenza titers than RD-Ad-vaccinated animals after challenge with influenza A/PR/8/34 virus. These data suggest that SC-Ads may be more potent vaccine platforms than conventional RD-Ad vectors and may have utility as "needle-free" mucosal vaccines.

Original languageEnglish (US)
Article numbere00720-16
JournalJournal of Virology
Volume91
Issue number2
DOIs
StatePublished - 2017

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Influenza Vaccines
Adenoviridae
influenza
vaccines
Hemagglutinins
Adenovirus Vaccines
Vaccines
Human Influenza
hemagglutinins
Mesocricetus
serotypes
Viral Vaccines
Sigmodon
Sigmodontinae
Genes
Viruses
Antigens
antigens
Hemagglutination
viruses

Keywords

  • Adenovirus
  • Gene-based vaccine
  • Replication defective
  • Single cycle

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Replicating single-cycle adenovirus vectors generate amplified influenza vaccine responses. / Crosby, Catherine M.; Matchett, William E.; Anguiano-Zarate, Stephanie S.; Parks, Christopher A.; Weaver, Eric A.; Pease, Larry R; Webby, Richard J.; Barry, Michael A.

In: Journal of Virology, Vol. 91, No. 2, e00720-16, 2017.

Research output: Contribution to journalArticle

Crosby, CM, Matchett, WE, Anguiano-Zarate, SS, Parks, CA, Weaver, EA, Pease, LR, Webby, RJ & Barry, MA 2017, 'Replicating single-cycle adenovirus vectors generate amplified influenza vaccine responses', Journal of Virology, vol. 91, no. 2, e00720-16. https://doi.org/10.1128/JVI.00720-16
Crosby, Catherine M. ; Matchett, William E. ; Anguiano-Zarate, Stephanie S. ; Parks, Christopher A. ; Weaver, Eric A. ; Pease, Larry R ; Webby, Richard J. ; Barry, Michael A. / Replicating single-cycle adenovirus vectors generate amplified influenza vaccine responses. In: Journal of Virology. 2017 ; Vol. 91, No. 2.
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