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

Publication Type
Journal Article
Year of Publication
2010
Authors
Koup, Richard A; Roederer, Mario; Lamoreaux, Laurie; Fischer, Jennifer; Novik, Laura; Nason, Martha C; Larkin, Brenda D; Enama, Mary E; Ledgerwood, Julie E; Bailer, Robert T; Mascola, John R; Nabel, Gary J; Graham, Barney S; VRC 009 Study Team; VRC 010 Study Team
Secondary
PLoS One
Volume
5
Pagination
e9015
Date Published
2010 Feb 02
Keywords
Adenoviridae; Adolescent; Adult; AIDS Vaccines; Antibodies, Viral; CD8-Positive T-Lymphocytes; Enzyme-Linked Immunosorbent Assay; Female; Flow cytometry; Genetic Vectors; HIV Infections; HIV-1; Humans; Immunization, Secondary; Immunophenotyping; Interferon-gamma; Male; T-Lymphocytes; Vaccines, DNA; Young Adult
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: ClinicalTrials.gov NCT00102089, NCT00108654.