title: Multiple factors affect immunogenicity of DNA plasmid HIV vaccines in human clinical trials.
abstract: Plasmid DNA vaccines have been licensed for use in domesticated animals because of their excellent immunogenicity, but none have yet been licensed for use in humans. Here we report a retrospective analysis of 1218 healthy human volunteers enrolled in 10 phase I clinical trials in which DNA plasmids encoding HIV antigens were administered. Elicited T-cell immune responses were quantified by validated intracellular cytokine staining (ICS) stimulated with HIV peptide pools. HIV-specific binding and neutralizing antibody activities were also analyzed using validated assays. Results showed that, in the absence of adjuvants and boosting with alternative vaccines, DNA vaccines elicited CD8+ and CD4+ T-cell responses in an average of 13.3% (95% CI: 9.8-17.8%) and 37.7% (95% CI: 31.9-43.8%) of vaccine recipients, respectively. Three vaccinations (vs. 2) improved the proportion of subjects with antigen-specific CD8+ responses (p=0.02), as did increased DNA dosage (p=0.007). Furthermore, female gender and participants having a lower body mass index were independently associated with higher CD4+ T-cell response rate (p=0.001 and p=0.008, respectively). These vaccines elicited minimal neutralizing and binding antibody responses. These findings of the immunogenicity of HIV DNA vaccines in humans can provide guidance for future clinical trials.
authors.affiliation: Infectious Diseases Division, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 689, Rochester, NY 14642-0002, United States. Electronic address: xjin@ips.ac.cn.
authors.forename: Xia
authors.initials: X
authors.lastname: Jin
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, PO Box 19204, Seattle, WA 98109-1024, United States. Electronic address: cmorgan@fredhutch.org.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Morgan
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, PO Box 19204, Seattle, WA 98109-1024, United States. Electronic address: xyu@scharp.org.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Yu
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, PO Box 19204, Seattle, WA 98109-1024, United States. Electronic address: sderosa@fredhutch.org.
authors.forename: Stephen
authors.initials: S
authors.lastname: DeRosa
authors.affiliation: Duke University Medical Center, 106 Research Drive, Durham, NC 27710, United States. Electronic address: georgia.tomaras@duke.edu.
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: Duke University Medical Center, 106 Research Drive, Durham, NC 27710, United States. Electronic address: david.montefiori@duke.edu.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, PO Box 19204, Seattle, WA 98109-1024, United States. Electronic address: jkublin@fredhutch.org.
authors.forename: James
authors.initials: J
authors.lastname: Kublin
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, PO Box 19204, Seattle, WA 98109-1024, United States. Electronic address: lcorey@fredhutch.org.
authors.forename: Larry
authors.initials: L
authors.lastname: Corey
authors.affiliation: Infectious Diseases Division, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 689, Rochester, NY 14642-0002, United States. Electronic address: michael_keefer@urmc.rochester.edu.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Keefer
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000276:Adjuvants, Immunologic; D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology; D015488:HIV Antigens / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D064368:Healthy Volunteers; D006801:Humans; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010957:Plasmids; D012189:Retrospective Studies; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology*; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D015483:HIV Antibodies; D015488:HIV Antigens; D019444:Vaccines, DNA; D007371:Interferon-gamma
keywords: Clinical trial; DNA vaccine; HIV; Immune response
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