Multiple factors affect immunogenicity of DNA plasmid HIV vaccines in human clinical trials
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..
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:33 |
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| Enthalten in: |
Vaccine - 33(2015), 20, Seite 2347-2353 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jin, Xia [VerfasserIn] |
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| Links: |
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| doi: |
10.1016/j.vaccine.2015.03.036 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Multiple factors affect immunogenicity of DNA plasmid HIV vaccines in human clinical trials |
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| 520 | |a 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. | ||
| 540 | |a Nutzungsrecht: Copyright © 2015 Elsevier Ltd. All rights reserved. | ||
| 650 | 4 | |a HIV-1 - genetics | |
| 650 | 4 | |a Vaccines, DNA - immunology | |
| 650 | 4 | |a AIDS Vaccines - immunology | |
| 650 | 4 | |a HIV Antigens - immunology | |
| 650 | 4 | |a CD8-Positive T-Lymphocytes - immunology | |
| 650 | 4 | |a AIDS Vaccines - administration & dosage | |
| 650 | 4 | |a CD4-Positive T-Lymphocytes - immunology | |
| 650 | 4 | |a Vaccines, DNA - administration & dosage | |
| 650 | 4 | |a HIV-1 - immunology | |
| 650 | 4 | |a HIV Antibodies - blood | |
| 650 | 4 | |a HIV Antibodies - immunology | |
| 650 | 4 | |a Interferon-gamma - immunology | |
| 700 | 1 | |a Morgan, Cecilia |4 oth | |
| 700 | 1 | |a Yu, Xuesong |4 oth | |
| 700 | 1 | |a DeRosa, Stephen |4 oth | |
| 700 | 1 | |a Tomaras, Georgia D |4 oth | |
| 700 | 1 | |a Montefiori, David C |4 oth | |
| 700 | 1 | |a Kublin, James |4 oth | |
| 700 | 1 | |a Corey, Larry |4 oth | |
| 700 | 1 | |a Keefer, Michael C |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |t Vaccine |d Amsterdam : Elsevier, 1983 |g 33(2015), 20, Seite 2347-2353 |w (DE-627)130402427 |w (DE-600)605674-X |w (DE-576)015904938 |x 0264-410X |7 nnns |
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| 856 | 4 | 1 | |u http://dx.doi.org/10.1016/j.vaccine.2015.03.036 |3 Volltext |
| 856 | 4 | 2 | |u http://www.ncbi.nlm.nih.gov/pubmed/25820067 |
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