Clinical MedicineIn-Press PreviewAIDS/HIVClinical trials Open Access | 10.1172/jci.insight.180819
1Division of Infectious Diseases, Vanderbilt University Medical Center, Nahville, United States of America
2Human Retrovirus Pathogenesis Section, NCI, Frederick, United States of America
3Departments of Microbiology, Medicine and Global Health, University of Washington, Seattle, United States of America
4San Francisco Department of Public Health and Department of Medicine, UCSF, San Francisco, United States of America
5National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States of America
6Division of Vaccine and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, United States of America
7Surgery, Duke University Medical Center, Durham, United States of America
8Human Retrovirus Pathogenesis Section, National Cancer Institute at Frederick, Frederick, United States of America
9Division of AIDS, National Institutes of Health, Bethesda, United States of America
10Immunology, Auro Vaccines LLC, Pearl River, United States of America
11N/A, Ichor Medical Systems, Inc., San Diego, United States of America
12Vaccine & Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America
13Human Retrovirus Section, National Cancer Institute, Frederick, United States of America
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1Division of Infectious Diseases, Vanderbilt University Medical Center, Nahville, United States of America
2Human Retrovirus Pathogenesis Section, NCI, Frederick, United States of America
3Departments of Microbiology, Medicine and Global Health, University of Washington, Seattle, United States of America
4San Francisco Department of Public Health and Department of Medicine, UCSF, San Francisco, United States of America
5National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States of America
6Division of Vaccine and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, United States of America
7Surgery, Duke University Medical Center, Durham, United States of America
8Human Retrovirus Pathogenesis Section, National Cancer Institute at Frederick, Frederick, United States of America
9Division of AIDS, National Institutes of Health, Bethesda, United States of America
10Immunology, Auro Vaccines LLC, Pearl River, United States of America
11N/A, Ichor Medical Systems, Inc., San Diego, United States of America
12Vaccine & Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America
13Human Retrovirus Section, National Cancer Institute, Frederick, United States of America
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1Division of Infectious Diseases, Vanderbilt University Medical Center, Nahville, United States of America
2Human Retrovirus Pathogenesis Section, NCI, Frederick, United States of America
3Departments of Microbiology, Medicine and Global Health, University of Washington, Seattle, United States of America
4San Francisco Department of Public Health and Department of Medicine, UCSF, San Francisco, United States of America
5National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States of America
6Division of Vaccine and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, United States of America
7Surgery, Duke University Medical Center, Durham, United States of America
8Human Retrovirus Pathogenesis Section, National Cancer Institute at Frederick, Frederick, United States of America
9Division of AIDS, National Institutes of Health, Bethesda, United States of America
10Immunology, Auro Vaccines LLC, Pearl River, United States of America
11N/A, Ichor Medical Systems, Inc., San Diego, United States of America
12Vaccine & Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America
13Human Retrovirus Section, National Cancer Institute, Frederick, United States of America
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1Division of Infectious Diseases, Vanderbilt University Medical Center, Nahville, United States of America
2Human Retrovirus Pathogenesis Section, NCI, Frederick, United States of America
3Departments of Microbiology, Medicine and Global Health, University of Washington, Seattle, United States of America
4San Francisco Department of Public Health and Department of Medicine, UCSF, San Francisco, United States of America
5National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States of America
6Division of Vaccine and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, United States of America
7Surgery, Duke University Medical Center, Durham, United States of America
8Human Retrovirus Pathogenesis Section, National Cancer Institute at Frederick, Frederick, United States of America
9Division of AIDS, National Institutes of Health, Bethesda, United States of America
10Immunology, Auro Vaccines LLC, Pearl River, United States of America
11N/A, Ichor Medical Systems, Inc., San Diego, United States of America
12Vaccine & Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America
13Human Retrovirus Section, National Cancer Institute, Frederick, United States of America
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1Division of Infectious Diseases, Vanderbilt University Medical Center, Nahville, United States of America
2Human Retrovirus Pathogenesis Section, NCI, Frederick, United States of America
3Departments of Microbiology, Medicine and Global Health, University of Washington, Seattle, United States of America
4San Francisco Department of Public Health and Department of Medicine, UCSF, San Francisco, United States of America
5National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States of America
6Division of Vaccine and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, United States of America
7Surgery, Duke University Medical Center, Durham, United States of America
8Human Retrovirus Pathogenesis Section, National Cancer Institute at Frederick, Frederick, United States of America
9Division of AIDS, National Institutes of Health, Bethesda, United States of America
10Immunology, Auro Vaccines LLC, Pearl River, United States of America
11N/A, Ichor Medical Systems, Inc., San Diego, United States of America
12Vaccine & Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America
13Human Retrovirus Section, National Cancer Institute, Frederick, United States of America
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1Division of Infectious Diseases, Vanderbilt University Medical Center, Nahville, United States of America
2Human Retrovirus Pathogenesis Section, NCI, Frederick, United States of America
3Departments of Microbiology, Medicine and Global Health, University of Washington, Seattle, United States of America
4San Francisco Department of Public Health and Department of Medicine, UCSF, San Francisco, United States of America
5National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States of America
6Division of Vaccine and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, United States of America
7Surgery, Duke University Medical Center, Durham, United States of America
8Human Retrovirus Pathogenesis Section, National Cancer Institute at Frederick, Frederick, United States of America
9Division of AIDS, National Institutes of Health, Bethesda, United States of America
10Immunology, Auro Vaccines LLC, Pearl River, United States of America
11N/A, Ichor Medical Systems, Inc., San Diego, United States of America
12Vaccine & Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America
13Human Retrovirus Section, National Cancer Institute, Frederick, United States of America
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1Division of Infectious Diseases, Vanderbilt University Medical Center, Nahville, United States of America
2Human Retrovirus Pathogenesis Section, NCI, Frederick, United States of America
3Departments of Microbiology, Medicine and Global Health, University of Washington, Seattle, United States of America
4San Francisco Department of Public Health and Department of Medicine, UCSF, San Francisco, United States of America
5National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States of America
6Division of Vaccine and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, United States of America
7Surgery, Duke University Medical Center, Durham, United States of America
8Human Retrovirus Pathogenesis Section, National Cancer Institute at Frederick, Frederick, United States of America
9Division of AIDS, National Institutes of Health, Bethesda, United States of America
10Immunology, Auro Vaccines LLC, Pearl River, United States of America
11N/A, Ichor Medical Systems, Inc., San Diego, United States of America
12Vaccine & Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America
13Human Retrovirus Section, National Cancer Institute, Frederick, United States of America
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1Division of Infectious Diseases, Vanderbilt University Medical Center, Nahville, United States of America
2Human Retrovirus Pathogenesis Section, NCI, Frederick, United States of America
3Departments of Microbiology, Medicine and Global Health, University of Washington, Seattle, United States of America
4San Francisco Department of Public Health and Department of Medicine, UCSF, San Francisco, United States of America
5National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States of America
6Division of Vaccine and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, United States of America
7Surgery, Duke University Medical Center, Durham, United States of America
8Human Retrovirus Pathogenesis Section, National Cancer Institute at Frederick, Frederick, United States of America
9Division of AIDS, National Institutes of Health, Bethesda, United States of America
10Immunology, Auro Vaccines LLC, Pearl River, United States of America
11N/A, Ichor Medical Systems, Inc., San Diego, United States of America
12Vaccine & Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America
13Human Retrovirus Section, National Cancer Institute, Frederick, United States of America
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1Division of Infectious Diseases, Vanderbilt University Medical Center, Nahville, United States of America
2Human Retrovirus Pathogenesis Section, NCI, Frederick, United States of America
3Departments of Microbiology, Medicine and Global Health, University of Washington, Seattle, United States of America
4San Francisco Department of Public Health and Department of Medicine, UCSF, San Francisco, United States of America
5National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States of America
6Division of Vaccine and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, United States of America
7Surgery, Duke University Medical Center, Durham, United States of America
8Human Retrovirus Pathogenesis Section, National Cancer Institute at Frederick, Frederick, United States of America
9Division of AIDS, National Institutes of Health, Bethesda, United States of America
10Immunology, Auro Vaccines LLC, Pearl River, United States of America
11N/A, Ichor Medical Systems, Inc., San Diego, United States of America
12Vaccine & Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America
13Human Retrovirus Section, National Cancer Institute, Frederick, United States of America
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1Division of Infectious Diseases, Vanderbilt University Medical Center, Nahville, United States of America
2Human Retrovirus Pathogenesis Section, NCI, Frederick, United States of America
3Departments of Microbiology, Medicine and Global Health, University of Washington, Seattle, United States of America
4San Francisco Department of Public Health and Department of Medicine, UCSF, San Francisco, United States of America
5National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States of America
6Division of Vaccine and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, United States of America
7Surgery, Duke University Medical Center, Durham, United States of America
8Human Retrovirus Pathogenesis Section, National Cancer Institute at Frederick, Frederick, United States of America
9Division of AIDS, National Institutes of Health, Bethesda, United States of America
10Immunology, Auro Vaccines LLC, Pearl River, United States of America
11N/A, Ichor Medical Systems, Inc., San Diego, United States of America
12Vaccine & Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America
13Human Retrovirus Section, National Cancer Institute, Frederick, United States of America
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1Division of Infectious Diseases, Vanderbilt University Medical Center, Nahville, United States of America
2Human Retrovirus Pathogenesis Section, NCI, Frederick, United States of America
3Departments of Microbiology, Medicine and Global Health, University of Washington, Seattle, United States of America
4San Francisco Department of Public Health and Department of Medicine, UCSF, San Francisco, United States of America
5National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States of America
6Division of Vaccine and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, United States of America
7Surgery, Duke University Medical Center, Durham, United States of America
8Human Retrovirus Pathogenesis Section, National Cancer Institute at Frederick, Frederick, United States of America
9Division of AIDS, National Institutes of Health, Bethesda, United States of America
10Immunology, Auro Vaccines LLC, Pearl River, United States of America
11N/A, Ichor Medical Systems, Inc., San Diego, United States of America
12Vaccine & Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America
13Human Retrovirus Section, National Cancer Institute, Frederick, United States of America
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1Division of Infectious Diseases, Vanderbilt University Medical Center, Nahville, United States of America
2Human Retrovirus Pathogenesis Section, NCI, Frederick, United States of America
3Departments of Microbiology, Medicine and Global Health, University of Washington, Seattle, United States of America
4San Francisco Department of Public Health and Department of Medicine, UCSF, San Francisco, United States of America
5National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States of America
6Division of Vaccine and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, United States of America
7Surgery, Duke University Medical Center, Durham, United States of America
8Human Retrovirus Pathogenesis Section, National Cancer Institute at Frederick, Frederick, United States of America
9Division of AIDS, National Institutes of Health, Bethesda, United States of America
10Immunology, Auro Vaccines LLC, Pearl River, United States of America
11N/A, Ichor Medical Systems, Inc., San Diego, United States of America
12Vaccine & Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America
13Human Retrovirus Section, National Cancer Institute, Frederick, United States of America
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1Division of Infectious Diseases, Vanderbilt University Medical Center, Nahville, United States of America
2Human Retrovirus Pathogenesis Section, NCI, Frederick, United States of America
3Departments of Microbiology, Medicine and Global Health, University of Washington, Seattle, United States of America
4San Francisco Department of Public Health and Department of Medicine, UCSF, San Francisco, United States of America
5National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States of America
6Division of Vaccine and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, United States of America
7Surgery, Duke University Medical Center, Durham, United States of America
8Human Retrovirus Pathogenesis Section, National Cancer Institute at Frederick, Frederick, United States of America
9Division of AIDS, National Institutes of Health, Bethesda, United States of America
10Immunology, Auro Vaccines LLC, Pearl River, United States of America
11N/A, Ichor Medical Systems, Inc., San Diego, United States of America
12Vaccine & Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America
13Human Retrovirus Section, National Cancer Institute, Frederick, United States of America
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1Division of Infectious Diseases, Vanderbilt University Medical Center, Nahville, United States of America
2Human Retrovirus Pathogenesis Section, NCI, Frederick, United States of America
3Departments of Microbiology, Medicine and Global Health, University of Washington, Seattle, United States of America
4San Francisco Department of Public Health and Department of Medicine, UCSF, San Francisco, United States of America
5National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States of America
6Division of Vaccine and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, United States of America
7Surgery, Duke University Medical Center, Durham, United States of America
8Human Retrovirus Pathogenesis Section, National Cancer Institute at Frederick, Frederick, United States of America
9Division of AIDS, National Institutes of Health, Bethesda, United States of America
10Immunology, Auro Vaccines LLC, Pearl River, United States of America
11N/A, Ichor Medical Systems, Inc., San Diego, United States of America
12Vaccine & Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America
13Human Retrovirus Section, National Cancer Institute, Frederick, United States of America
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1Division of Infectious Diseases, Vanderbilt University Medical Center, Nahville, United States of America
2Human Retrovirus Pathogenesis Section, NCI, Frederick, United States of America
3Departments of Microbiology, Medicine and Global Health, University of Washington, Seattle, United States of America
4San Francisco Department of Public Health and Department of Medicine, UCSF, San Francisco, United States of America
5National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States of America
6Division of Vaccine and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, United States of America
7Surgery, Duke University Medical Center, Durham, United States of America
8Human Retrovirus Pathogenesis Section, National Cancer Institute at Frederick, Frederick, United States of America
9Division of AIDS, National Institutes of Health, Bethesda, United States of America
10Immunology, Auro Vaccines LLC, Pearl River, United States of America
11N/A, Ichor Medical Systems, Inc., San Diego, United States of America
12Vaccine & Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America
13Human Retrovirus Section, National Cancer Institute, Frederick, United States of America
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1Division of Infectious Diseases, Vanderbilt University Medical Center, Nahville, United States of America
2Human Retrovirus Pathogenesis Section, NCI, Frederick, United States of America
3Departments of Microbiology, Medicine and Global Health, University of Washington, Seattle, United States of America
4San Francisco Department of Public Health and Department of Medicine, UCSF, San Francisco, United States of America
5National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States of America
6Division of Vaccine and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, United States of America
7Surgery, Duke University Medical Center, Durham, United States of America
8Human Retrovirus Pathogenesis Section, National Cancer Institute at Frederick, Frederick, United States of America
9Division of AIDS, National Institutes of Health, Bethesda, United States of America
10Immunology, Auro Vaccines LLC, Pearl River, United States of America
11N/A, Ichor Medical Systems, Inc., San Diego, United States of America
12Vaccine & Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America
13Human Retrovirus Section, National Cancer Institute, Frederick, United States of America
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1Division of Infectious Diseases, Vanderbilt University Medical Center, Nahville, United States of America
2Human Retrovirus Pathogenesis Section, NCI, Frederick, United States of America
3Departments of Microbiology, Medicine and Global Health, University of Washington, Seattle, United States of America
4San Francisco Department of Public Health and Department of Medicine, UCSF, San Francisco, United States of America
5National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States of America
6Division of Vaccine and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, United States of America
7Surgery, Duke University Medical Center, Durham, United States of America
8Human Retrovirus Pathogenesis Section, National Cancer Institute at Frederick, Frederick, United States of America
9Division of AIDS, National Institutes of Health, Bethesda, United States of America
10Immunology, Auro Vaccines LLC, Pearl River, United States of America
11N/A, Ichor Medical Systems, Inc., San Diego, United States of America
12Vaccine & Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America
13Human Retrovirus Section, National Cancer Institute, Frederick, United States of America
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1Division of Infectious Diseases, Vanderbilt University Medical Center, Nahville, United States of America
2Human Retrovirus Pathogenesis Section, NCI, Frederick, United States of America
3Departments of Microbiology, Medicine and Global Health, University of Washington, Seattle, United States of America
4San Francisco Department of Public Health and Department of Medicine, UCSF, San Francisco, United States of America
5National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States of America
6Division of Vaccine and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, United States of America
7Surgery, Duke University Medical Center, Durham, United States of America
8Human Retrovirus Pathogenesis Section, National Cancer Institute at Frederick, Frederick, United States of America
9Division of AIDS, National Institutes of Health, Bethesda, United States of America
10Immunology, Auro Vaccines LLC, Pearl River, United States of America
11N/A, Ichor Medical Systems, Inc., San Diego, United States of America
12Vaccine & Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America
13Human Retrovirus Section, National Cancer Institute, Frederick, United States of America
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Published August 1, 2024 - More info
BACKGROUND. An HIV-1 DNA vaccine composed of seven highly conserved, structurally important elements (Conserved Elements, CE) of HIV p24Gag was tested in a phase I randomized, double-blind clinical trial (HVTN 119, NCT03181789) in people without HIV. A CE prime- CE+full-length p55Gag boost DNA vaccine was compared to p55Gag DNA vaccination only. METHODS. Two groups (n=25 each) received 4 DNA vaccinations [2xCE prime- 2xCE+p55Gag boost or 4x p55Gag] by intramuscular injection/electroporation, including IL-12 DNA adjuvant. The placebo group (n=6) received saline. Participants were followed for safety and tolerability. Immunogenicity was assessed for T cell and antibody responses. RESULTS. Both regimens were safe and generally well-tolerated. The p24CE vaccine was immunogenic (29% CD4+ and 4% CD8+ responders) and was significantly boosted by CE+p55Gag (64% CD4+, p=0.037; 42% CD8+, p=0.004). CE+p55Gag induced CD4+ responses to 5 of 7 CE, compared to only 2 CE by p55Gag DNA alone, with a higher reponse to CE5 in 30% of individuals (p=0.006). CE+p55Gag induced significantly higher mean CD4+ CE Tcell breadth (0.68 vs 0.22 CE; p=0.029) and a strong trend for increased CD4+ and CD8+ T-cell breadth (1.14 vs. 0.52 CE; p=0.051) compared to p55Gag alone. Both groups developed high p55Gag T-cell (91% each) and p24Gag antibody (91% vs. 80%) responses. p24CE vaccine-induced CD4+ CE T-cell responses correlated (p=0.007) with p24Gag antibody responses. CONCLUSION. The combination CE/CE+p55Gag DNA vaccine induced T-cell immune responses to conserved regions in p24Gag resulting in significant increases in breadth and epitope recognition throughout p55Gag. Vaccines able to focus immune responses by priming responses to highly conserved regions could be part of a comprehensive HIV vaccine strategy. TRIAL REGISTRATION. Clinical Trials.gov NCT03181789 Study URL: https://www.clinicaltrials.gov/search?term=NCT03181789 FUNDING. HIV vaccine trial network (HVTN), NIAID/NIH