Priming immunization with DNA augments immunogenicity of recombinant adenoviral vectors for both HIV-1 specific antibody and T-cell responses

Richard A. Koup, Mario Roederer, Laurie Lamoreaux, Jennifer Fischer, Laura Novik, Martha C. Nason, Brenda D. Larkin, Mary E. Enama, Julie E. Ledgerwood, Robert T. Bailer, John R. Mascola, Gary J. Nabel, Barney S. Graham, Margaret McCluskey, Sarah Hubka, Lasonji Holman, Ingelise Gordon, Pamela Edmonds, Steve Rucker, Joseph CasazzaAndrew Catanzaro, Alan Fix

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Abstract

Background: Induction of HIV-1-specific T-cell responses relevant to diverse subtypes is a major goal of HIV vaccine development. Prime-boost regimens using heterologous gene-based vaccine vectors have induced potent, polyfunctional T cell responses in preclinical studies. Methods: The first opportunity to evaluate the immunogenicity of DNA priming followed by recombinant adenovirus serotype 5 (rAd5) boosting was as open-label rollover trials in subjects who had been enrolled in prior studies of HIV-1 specific DNA vaccines. All subjects underwent apheresis before and after rAd5 boosting to characterize in depth the T cell and antibody response induced by the heterologous DNA/rAd5 prime-boost combination. Results: rAd5 boosting was well-tolerated with no serious adverse events. Compared to DNA or rAd5 vaccine alone, sequential DNA/rAd5 administration induced 7-fold higher magnitude Env-biased HIV-1-specific CD8+ T-cell responses and 100-fold greater antibody titers measured by ELISA. There was no significant neutralizing antibody activity against primary isolates. Vaccine-elicited CD4+ and CD8+ T-cells expressed multiple functions and were predominantly long-term (CD127+) central or effector memory T cells and that persisted in blood for >6 months. Epitopes mapped in Gag and Env demonstrated partial cross-clade recognition. Conclusion: Heterologous prime-boost using vector-based gene delivery of vaccine antigens is a potent immunization strategy for inducing both antibody and T-cell responses. Trial Registration: ClinicalTrails.gov NCT00102089, NCT00108654.

Original languageEnglish (US)
Article numbere9015
JournalPLoS One
Volume5
Issue number2
DOIs
StatePublished - Feb 2 2010
Externally publishedYes

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Koup, R. A., Roederer, M., Lamoreaux, L., Fischer, J., Novik, L., Nason, M. C., Larkin, B. D., Enama, M. E., Ledgerwood, J. E., Bailer, R. T., Mascola, J. R., Nabel, G. J., Graham, B. S., McCluskey, M., Hubka, S., Holman, L., Gordon, I., Edmonds, P., Rucker, S., ... Fix, A. (2010). Priming immunization with DNA augments immunogenicity of recombinant adenoviral vectors for both HIV-1 specific antibody and T-cell responses. PLoS One, 5(2), [e9015]. https://doi.org/10.1371/journal.pone.0009015