This is a multicenter, open-label, phase 1 clinical trial to test two human immunodeficiency virus (HIV) vaccines with two adjuvants. An adjuvant is an ingredient used with some vaccines that may help people make an immune response. HIV is the virus that causes acquired immunodeficiency syndrome (AIDS). About 42 people will take part in the HVTN 309 clinical trial. This clinical trial will take place at multiple sites in the US and South Africa and the clinical trial is divided into 3 parts: Part A, Part B and Part C. About 3 people will participate in Part A of this study. After results from Part A are reviewed, it will be determined whether or not Part B and Part C of the clinical trial will proceed.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
A ferritin NP expressing 8 copies of an HIV-1 Env protein trimer. To be administered intramuscularly (IM).
A stabilized chimeric SOSIP Env trimer protein with the N-terminal sequence of CH505 TF gp120 Env transplanted into the BG505 SOSIP sequence. To be administered IM.
An aqueous formulation (AF) of the small molecule imidazoquinoline immune response modifier (IRM) 3M-052; toll-like receptor (TLR)7/8 agonist.
Alum to be administered IM as 500 mcg (aluminum content) admixed with 3M-052-AF (5 mcg) along with CD4BS CH505M5 Pr-NP1 and CH505 TF chTrimer.
An AF consisting of 4 lipid components.
Alabama CRS (Site ID: 31788)
Birmingham, Alabama, United States
The Ponce de Leon Center CRS (Site ID: 5802)
Atlanta, Georgia, United States
Vanderbilt Vaccine (VV) CRS (Site ID: 30352)
Nashville, Tennessee, United States
Setshaba Research Centre CRS (Site ID: 31829)
Soshanguve, Gauteng, South Africa
Isipingo CRS (Site ID: 31635)
Isipingo, KwaZulu-Natal, South Africa
Klerksdorp CRS (Site ID: 30325)
Klerksdorp, North West, South Africa
Frequency of local reactogenicity signs and symptoms after receipt of any study vaccine
Time frame: Part A: Day 15, 71, and 127; Part B: Day 15, 71, 127, 183, and 239; Part C: 15, 71, 127, 183, and 239 (14 days following receipt of any study vaccine)
Frequency of systemic reactogenicity signs and symptoms after receipt of any study vaccine
Time frame: Part A: Day 15, 71, and 127; Part B: Day 15, 71, 127, 183, and 239; Part C: 15, 71, 127, 183, and 239 (14 days following receipt of any study vaccine)
Number of serious adverse events (SAEs) leading to early participant withdrawal or permanent discontinuation
Time frame: 31 months
Number of medically attended adverse events (MAAEs) leading to early participant withdrawal or permanent discontinuation
Time frame: 31 months
Number of adverse events of special interest (AESIs) leading to early participant withdrawal or permanent discontinuation
Time frame: 31 months
Number of adverse events (AEs) leading to early participant withdrawal or permanent discontinuation
Time frame: 31 months
Part C only: Frequency of the CD4BS and CH505M5, G458Y, GNT1-specific, N280D KO IgG+ memory B cells, as assessed by flow cytometry
Time frame: Part C: Day 127 and 239 (2 weeks after the third and fifth vaccinations respectively)
Part C only: Response rate of serum Ab neutralization of vaccine-matched tier 2 HIV-1 strains as measured by TZM-bl assay
Time frame: Part C: Day 127 and 239 (2 weeks after the third and fifth vaccinations respectively)
Part C only: Magnitude of serum Ab neutralization of vaccine-matched tier 2 HIV-1 strains as measured by TZM-bl assay
Time frame: Part C: Day 127 and 239 (2 weeks after the third and fifth vaccinations respectively)
Parts B and C: Response rate of serum IgG binding Abs to autologous and heterologous HIV Env stabilized trimers, as assessed by binding antibody multiplex assay (BAMA)
Time frame: Part B: Day 127 and 239; Part C: Day 127 and 239 (2 weeks after the third and fifth vaccinations, respectively, in each part)
Parts B and C: Magnitude of serum IgG binding Abs to autologous and heterologous HIV Env stabilized trimers, as assessed by binding antibody multiplex assay (BAMA)
Time frame: Part B: Day 127 and 239; Part C: Day 127 and 239 (2 weeks after the third and fifth vaccinations, respectively, in each part)
Part B only: Response rate of serum Ab neutralization of vaccine-matched tier 2 HIV-1 strains as measured by the TZM-bl assay
Time frame: Part B: Day 127 and 239 (2 weeks after the third and fifth vaccinations respectively)
Part B only: Magnitude of serum Ab neutralization of vaccine-matched tier 2 HIV-1 strains as measured by the TZM-bl assay
Time frame: Part B: Day 127 and 239 (2 weeks after the third and fifth vaccinations respectively)
Parts B and C: Response rate of differential serum Ab neutralization of precursor detection virus and corresponding epitope KO virus, as measured by TZM-bl assay
Time frame: Part B: Day 127 and 239; Part C: Day 127 and 239 (2 weeks after the third and fifth vaccinations, respectively, in each part)
Parts B and C: Magnitude of differential serum Ab neutralization of precursor detection virus and corresponding epitope KO virus, as measured by TZM-bl assay
Time frame: Part B: Day 127 and 239; Part C: Day 127 and 239 (2 weeks after the third and fifth vaccinations, respectively, in each part)
Parts B and C: Response rate of serum Ab neutralization of heterologous HIV-1 strains, as measured by TZM-bl assay
Time frame: Part B: Day 127 and 239; Part C: Day 127 and 239 (2 weeks after the third and fifth vaccinations, respectively, in each part)
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Parts B and C: Magnitude of serum Ab neutralization of heterologous HIV-1 strains, as measured by TZM-bl assay
Time frame: Part B: Day 127 and 239; Part C: Day 127 and 239 (2 weeks after the third and fifth vaccinations, respectively, in each part)
Parts B and C: Response rate of CD4+ and CD8+ T-cell responses, as measured by flow cytometry
Time frame: Part B: Day 127 and 239; Part C: Day 127 and 239 (2 weeks after the third and fifth vaccinations, respectively, in each part)
Parts B and C: Magnitude of CD4+ and CD8+ T-cell responses, as measured by flow cytometry
Time frame: Part B: Day 127 and 239; Part C: Day 127 and 239 (2 weeks after the third and fifth vaccinations, respectively, in each part)
Part B only: Frequency of the CD4BS and CH505M5, G458Y, GNT1-specific, N280D KO IgG+ memory B cells, as assessed by flow cytometry
Time frame: Part B: Day 127 and 239 (2 weeks after the third and fifth vaccinations respectively)