Vector choice determines immunogenicity and potency of genetic vaccines against Angola Marburg virus in nonhuman primates

Thomas Geisbert, Michael Bailey, Joan B. Geisbert, Clement Asiedu, Mario Roederer, Maria Grazia-Pau, Jerome Custers, Peter Jahrling, Jaap Goudsmit, Richard Koup, Nancy J. Sullivan

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

The immunogenicity and durability of genetic vaccines are influenced by the composition of gene inserts and choice of delivery vector. DNA vectors are a promising vaccine approach showing efficacy when combined in prime-boost regimens with recombinant protein or viral vectors, but they have shown limited comparative efficacy as a stand-alone platform in primates, due possibly to suboptimal gene expression or cell targeting. Here, regimens using DNA plasmids modified for optimal antigen expression and recombinant adenovirus (rAd) vectors, all encoding the glycoprotein (GP) gene from Angola Marburg virus (MARV), were compared for their ability to provide immune protection against lethal MARV Angola infection. Heterologous DNA-GP/rAd5-GP prime-boost and single-modality rAd5-GP, as well as the DNA-GP-only vaccine, prevented death in all vaccinated subjects after challenge with a lethal dose of MARV Angola. The DNA/DNA vaccine induced humoral responses comparable to those induced by a single inoculation with rAd5-GP, as well as CD4+ and CD8+ cellular immune responses, with skewing toward CD4+ T-cell activity against MARV GP. Vaccine regimens containing rAd-GP, alone or as a boost, exhibited cellular responses with CD8+ T-cell dominance. Across vaccine groups, CD8+ T-cell subset dominance comprising cells exhibiting a tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ) double-positive functional phenotype was associated with an absence or low frequency of clinical symptoms, suggesting that both the magnitude and functional phenotype of CD8+ T cells may determine vaccine efficacy against infection by MARV Angola.

Original languageEnglish (US)
Pages (from-to)10386-10394
Number of pages9
JournalJournal of Virology
Volume84
Issue number19
DOIs
StatePublished - 2010
Externally publishedYes

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Marburg virus
Marburgvirus
Angola
Vaccine Potency
Primates
glycoproteins
Glycoproteins
immune response
vaccines
Vaccines
T-lymphocytes
DNA
Adenoviridae
T-Lymphocytes
dominance (genetics)
Phenotype
phenotype
interferon-alpha
DNA Vaccines
lethal dose

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Medicine(all)

Cite this

Geisbert, T., Bailey, M., Geisbert, J. B., Asiedu, C., Roederer, M., Grazia-Pau, M., ... Sullivan, N. J. (2010). Vector choice determines immunogenicity and potency of genetic vaccines against Angola Marburg virus in nonhuman primates. Journal of Virology, 84(19), 10386-10394. https://doi.org/10.1128/JVI.00594-10

Vector choice determines immunogenicity and potency of genetic vaccines against Angola Marburg virus in nonhuman primates. / Geisbert, Thomas; Bailey, Michael; Geisbert, Joan B.; Asiedu, Clement; Roederer, Mario; Grazia-Pau, Maria; Custers, Jerome; Jahrling, Peter; Goudsmit, Jaap; Koup, Richard; Sullivan, Nancy J.

In: Journal of Virology, Vol. 84, No. 19, 2010, p. 10386-10394.

Research output: Contribution to journalArticle

Geisbert, T, Bailey, M, Geisbert, JB, Asiedu, C, Roederer, M, Grazia-Pau, M, Custers, J, Jahrling, P, Goudsmit, J, Koup, R & Sullivan, NJ 2010, 'Vector choice determines immunogenicity and potency of genetic vaccines against Angola Marburg virus in nonhuman primates', Journal of Virology, vol. 84, no. 19, pp. 10386-10394. https://doi.org/10.1128/JVI.00594-10
Geisbert, Thomas ; Bailey, Michael ; Geisbert, Joan B. ; Asiedu, Clement ; Roederer, Mario ; Grazia-Pau, Maria ; Custers, Jerome ; Jahrling, Peter ; Goudsmit, Jaap ; Koup, Richard ; Sullivan, Nancy J. / Vector choice determines immunogenicity and potency of genetic vaccines against Angola Marburg virus in nonhuman primates. In: Journal of Virology. 2010 ; Vol. 84, No. 19. pp. 10386-10394.
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