Evaluating the Safety and Immunogenicity of HIV-1 BG505 SOSIP.664 gp140 With TLR Agonist and/or Alum Adjuvants in Healthy, HIV-uninfected Adults

A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of HIV-1 BG505 SOSIP.664 gp140 With TLR Agonist and/or Aalum Adjuvants and VRC HIV Env Trimer 4571 and 3M-052-AF With Alum in Healthy, HIV-uninfected Adults

The purpose of this study is to evaluate the safety and immunogenicity of HIV-1 BG505 SOSIP.664 gp140 with TLR agonist and/or alum adjuvants in healthy, HIV-uninfected adults.

Study Overview

• Status: Active, not recruiting
• Conditions: HIV Infections
• Intervention / Treatment: Biological: BG505 SOSIP.664 gp140; Biological: 3M-052-AF; Biological: Alum (Aluminum Hydroxide Suspension); Biological: Placebo; Biological: CpG 1018; Biological: GLA-LSQ; Biological: Trimer 4571

Detailed Description

This study will evaluate the safety and immunogenicity of HIV-1 BG505 SOSIP.664 gp140 with TLR agonist and/or alum adjuvants in healthy, HIV-uninfected adults.

The study will be conducted in three parts (Part A, B and C). Part A will include two groups (Groups 1 and 2), Part B will include four groups (Groups 3, 4, 5, and 6) and Part C will include two groups (Groups 7 and 8).

Participants in Part A will be randomly assigned to receive the BG505 SOSIP.664 gp140 vaccine admixed with 3M-052-AF and alum adjuvant or to receive placebo. Part A participants will be enrolled sequentially in Groups 1 and 2 for dose escalation.

Participants in Part B will be randomly assigned to Groups 3, 4, 5, or 6, to receive the BG505 SOSIP.664 gp140 vaccine with an adjuvant (the specific adjuvant will vary by group) or to receive placebo.

Participants in Part C will be randomly assigned to Groups 7 or 8 to receive the Trimer 4571 (BG505 SOSIP.664 DS gp140) with 3M-052-AF + Alum or to receive placebo.

Participants in Part A will attend 8 months of scheduled clinic visits, and they will be contacted by study staff at Month 14 for follow-up health monitoring. Participants in Part B will attend 18 months of scheduled clinic visits. Participants in Part C will attend 18 months of scheduled clinic visits.

• Study Type: Interventional
• Enrollment (Actual): 127
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Alabama CRS
  • Georgia
    • Atlanta, Georgia, United States, 30308-2012
      • The Ponce de Leon Center CRS
    • Decatur, Georgia, United States, 30030
      • The Hope Clinic of the Emory Vaccine Center CRS
  • Massachusetts
    • Boston, Massachusetts, United States, 02115-6110
      • Brigham and Women's Hospital Vaccine CRS (BWH VCRS)
  • New York
    • New York, New York, United States, 10032
      • Columbia P&S CRS
    • New York, New York, United States, 10065
      • New York Blood Center CRS (Site 31801)
    • Rochester, New York, United States, 14642
      • University of Rochester Vaccines to Prevent HIV Infection CRS
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Prevention CRS
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh CRS
  • Washington
    • Seattle, Washington, United States, 98109-1024
      • Seattle Vaccine and Prevention CRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

General and Demographic Criteria

• Age of 18 through 50 years, inclusive
• Access to a participating HIV Vaccine Trials Network (HVTN) clinical research site (CRS) and willingness to be followed for the planned duration of the study
• Ability and willingness to provide informed consent
• Assessment of understanding: volunteer demonstrates understanding of this; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly
• Agrees not to enroll in another study of an investigational research agent until after the final study contact.
• Good general health as shown by medical history, physical exam, and screening laboratory tests

HIV-Related Criteria:

• Willingness to receive HIV test results
• Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling
• Assessed by the clinic staff as being at "low risk" for HIV infection and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit (see study protocol for more information)

Laboratory Inclusion Values

Hemogram/Complete blood count (CBC)

• Hemoglobin

  • ≥ 11.0 g/dL for volunteers who were assigned female sex at birth
  • ≥ 13.0 g/dL for volunteers who were assigned male sex at birth and transgender males who have been on hormone therapy for more than 6 consecutive months
  • ≥ 12.0 g/dL for transgender females who have been on hormone therapy for more than 6 consecutive months
  • For transgender volunteers who have been on hormone therapy for less than 6 consecutive months, determine hemoglobin eligibility based on the sex assigned at birth.
• White blood cell count = 2,500 to 12,000 cells/mm^3 with normal differential, or differential approved by Investigator of Record (IoR) or designee as not clinically significant
• Total lymphocyte count ≥ 650 cells/mm^3 with normal differential, or differential approved by IoR or designee as not clinically significant
• Remaining differential either within institutional normal range or with IoR or designee approval
• Platelets = 125,000 to 550,000 cells/mm^3

Chemistry

• Alanine aminotransferase (ALT) < 1.25 times the institutional upper limit of normal
• Creatinine < 1.1 times the institutional upper limit of normal

Virology

• Negative HIV-1 and -2 blood test: US volunteers must have a negative U.S. Food and Drug Administration (FDA)-approved enzyme immunoassay (EIA) or chemiluminescent microparticle immunoassay (CMIA).
• Negative hepatitis B surface antigen (HBsAg)
• Negative anti-hepatitis C virus antibodies (anti-HCV), or negative HCV polymerase chain reaction (PCR) if the anti-HCV is positive

Urine

• Normal urine:

  • Negative or trace urine protein, and
  • Negative or trace urine hemoglobin (If trace hemoglobin is present on dipstick, a microscopic urinalysis with red blood cells levels within institutional normal range,)

Reproductive Status

• Volunteers who were assigned female sex at birth: negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test at screening (ie, prior to randomization) and prior to study product administration or any optional study procedure (eg, leukapheresis, fine needle aspirate, bone marrow aspiration, mucosal secretion collection or mucosal biopsy) on the day of study product administration or procedure. Persons who are NOT of reproductive potential due to having undergone hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing.

• Reproductive status: A volunteer who was assigned female sex at birth:

  • Must agree to use effective contraception for sexual activity that could lead to pregnancy from at least 21 days prior to enrollment until 6 months after the final study vaccination. Effective contraception is defined as using the following methods:

    • Condoms (male or female) with or without a spermicide,
    • Diaphragm or cervical cap with spermicide,
    • Intrauterine device (IUD),
    • Hormonal contraception,
    • Tubal ligation, or
    • Any other contraceptive method approved by the HVTN 137 Protocol Safety Review Team (PSRT)
    • Successful vasectomy in any partner assigned male sex at birth (considered successful if a volunteer reports that a male partner has [1] documentation of azoospermia by microscopy, or [2] a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity postvasectomy);
  • Or not be of reproductive potential, such as having reached menopause (no menses for 1 year) or having undergone hysterectomy or bilateral oophorectomy;
  • Or be sexually abstinent.
• Volunteers who were assigned female sex at birth must also agree not to seek pregnancy through alternative methods, such as artificial insemination or in vitro fertilization until 6 months after the last vaccination.

Exclusion Criteria:

General

• Blood products received within 120 days before first vaccination
• Investigational research agents received within 30 days before first vaccination
• Body mass index (BMI) ≥ 40; or BMI ≥ 35 with 2 or more of the following: age > 45, systolic blood pressure > 140 mm Hg, diastolic blood pressure > 90 mm Hg, current smoker, known hyperlipidemia
• Intent to participate in another study of an investigational research agent or any other study that requires non-HVTN HIV antibody testing during the planned duration of the HVTN 137 study
• Pregnant or breastfeeding
• Active duty and reserve US military personnel

Vaccines and other Injections

• HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 137 PSRT will determine eligibility on a case-by-case basis.
• Previous receipt of monoclonal antibodies (mAbs), whether licensed or investigational; the HVTN 137 PSRT will determine eligibility on a case-by-case basis
• Non-HIV experimental vaccine(s) received within the last 1 year in a prior vaccine trial. Exceptions may be made by the HVTN 137 PSRT for vaccines that have subsequently undergone licensure by the FDA. For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 137 PSRT will determine eligibility on a case-by-case basis. For volunteers who have received an experimental vaccine(s) greater than 1 year ago, eligibility for enrollment will be determined by the HVTN 137 PSRT on a case-by-case basis.
• Live attenuated vaccines received within 30 days before first vaccination or scheduled within 30 days after injection (eg, measles, mumps, and rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever; live attenuated influenza vaccine)
• Any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination or scheduled for 14 days after injection (eg, tetanus, pneumococcal, hepatitis virus A or B)
• Previous receipt of HEPLISAV, Shingrix, or RTS,S/AS01B/Mosquirix vaccine received within 30 days prior to first vaccination or scheduled for 30 days after injection.
• Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination

Immune System

• Immunosuppressive medications received within 168 days before first vaccination (Not exclusionary: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; [3] topical corticosteroids for mild, uncomplicated dermatologic condition; or [4] a single course of oral/parenteral prednisone or equivalent at doses ≤ 60 mg/day and length of therapy < 11 days with completion at least 30 days prior to enrollment)
• Serious adverse reactions to vaccines or to vaccine components, including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded from participation: a volunteer who had a non-anaphylactic adverse reaction to pertussis vaccine as a child.)
• Immunoglobulin received within 60 days before first vaccination (for mAb see criterion above)
• Autoimmune disease, current or history
• AESIs: Volunteers who currently have, or have a history of, any condition that could be considered an AESI for the product(s) administered in this protocol (representative examples are listed in the study protocol)
• Immunodeficiency

Clinically significant medical conditions

• Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to:

  • A process that would affect the immune response,
  • A process that would require medication that affects the immune response,
  • Any contraindication to repeated injections or blood draws,
  • A condition that requires active medical intervention or monitoring to avert grave danger to the volunteer's health or well-being during the study period,
  • A condition or process for which signs or symptoms could be confused with reactions to vaccine, or
  • Any condition specifically listed among the exclusion criteria below.
• Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or reactogenicity, or a volunteer's ability to give informed consent
• Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years.
• Current anti-tuberculosis (TB) prophylaxis or therapy

• Asthma other than mild, well-controlled asthma (Symptoms of asthma severity as defined in the most recent National Asthma Education and Prevention Program (NAEPP) Expert Panel report). Exclude a volunteer who:

  • Uses a short-acting rescue inhaler (typically a beta 2 agonist) daily, or
  • Uses moderate/high dose inhaled corticosteroids, or

  • In the past year has either of the following:

    • Greater than 1 exacerbation of symptoms treated with oral/parenteral corticosteroids;
    • Needed emergency care, urgent care, hospitalization, or intubation for asthma
• Diabetes mellitus type 1 or type 2 (Not exclusionary: type 2 cases controlled with diet alone or a history of isolated gestational diabetes.)
• Thyroidectomy, or thyroid disease requiring medication during the last 12 months

• Hypertension:

  • If a person has been found to have elevated blood pressure or hypertension during screening or previously, exclude for blood pressure that is not well controlled. Well-controlled blood pressure is defined in this protocol as consistently < 140 mm Hg systolic and ≤ 90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be ≤ 150 mm Hg systolic and ≤ 100 mm Hg diastolic. For these volunteers, blood pressure must be ≤ 140 mm Hg systolic and ≤ 90 mm Hg diastolic at enrollment.
  • If a person has NOT been found to have elevated blood pressure or hypertension during screening or previously, exclude for systolic blood pressure ≥ 150 mm Hg at enrollment or diastolic blood pressure ≥ 100 mm Hg at enrollment.
• Bleeding disorder (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions)
• Malignancy (Not excluded from participation: Volunteer who has had malignancy excised surgically and who, in the investigator's estimation, has a reasonable assurance of sustained cure, or who is unlikely to experience recurrence of malignancy during the period of the study)
• Seizure disorder: History of seizure(s) within past three years. Also exclude if volunteer has used medications in order to prevent or treat seizure(s) at any time within the past 3 years.
• Asplenia: any condition resulting in the absence of a functional spleen
• History of generalized urticaria, angioedema, or anaphylaxis. (Not exclusionary: angioedema or anaphylaxis to a known trigger with at least 5 years since last reaction to demonstrate satisfactory avoidance of trigger.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

16

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A, Group 1 (T1): BG505 SOSIP.664 gp140 + 3M-052-AF + Alum; Participants will receive 100 mcg of BG505 SOSIP.664 gp140, admixed with 1 mcg of 3M-052-AF and 500 mcg of Aluminum Hydroxide Suspension (Alum), as one intramuscular (IM) injection at Months 0 and 2.	Biological: BG505 SOSIP.664 gp140; Administered by IM injection; Biological: 3M-052-AF; Administered by IM injection; Biological: Alum (Aluminum Hydroxide Suspension); Administered by IM injection
Placebo Comparator: Part A, Group 1 (P1): Placebo; Participants will receive placebo as one IM injection at Months 0 and 2.	Biological: Placebo; Administered by IM injection
Experimental: Part A, Group 2 (T2): BG505 SOSIP.664 gp140 + 3M-052-AF + Alum; Participants will receive 100 mcg of BG505 SOSIP.664 gp140, admixed with 5 mcg of 3M-052-AF and 500 mcg of Alum, as one IM injection at Months 0 and 2.	Biological: BG505 SOSIP.664 gp140; Administered by IM injection; Biological: 3M-052-AF; Administered by IM injection; Biological: Alum (Aluminum Hydroxide Suspension); Administered by IM injection
Placebo Comparator: Part A, Group 2 (P2): Placebo; Participants will receive placebo as one IM injection at Months 0 and 2.	Biological: Placebo; Administered by IM injection
Experimental: Part B, Group 3 (T3): BG505 SOSIP.664 gp140 + CpG 1018 + Alum; Participants will receive 100 mcg of BG505 SOSIP.664 gp140, admixed with 300 mcg of CpG 1018 and 500 mcg of Alum, as one IM injection at Months 0, 2, and 6.	Biological: BG505 SOSIP.664 gp140; Administered by IM injection; Biological: Alum (Aluminum Hydroxide Suspension); Administered by IM injection; Biological: CpG 1018; Administered by IM injection
Placebo Comparator: Part B, Group 3 (P3): Placebo; Participants will receive placebo as one IM injection at Months 0, 2, and 6.	Biological: Placebo; Administered by IM injection
Experimental: Part B, Group 4 (T4): BG505 SOSIP.664 gp140 + 3M-052-AF + Alum; Participants will receive 100 mcg of BG505 SOSIP.664 gp140, admixed with either 1 mcg or 5 mcg of 3M-052-AF (the highest tolerated dose from Part A), and 500 mcg of Alum, as one IM injection at Months 0, 2, and 6.	Biological: BG505 SOSIP.664 gp140; Administered by IM injection; Biological: 3M-052-AF; Administered by IM injection; Biological: Alum (Aluminum Hydroxide Suspension); Administered by IM injection
Placebo Comparator: Group 4 (P4): Placebo; Participants will receive placebo as one IM injection at Months 0, 2, and 6.	Biological: Placebo; Administered by IM injection
Experimental: Part B, Group 5 (T5): BG505 SOSIP.664 gp140 + GLA-LSQ; Participants will receive 100 mcg of BG505 SOSIP.664 gp140, admixed with GLA-LSQ (GLA 5 mcg, and QS-21 2 mcg), as one IM injection at Months 0, 2, and 6.	Biological: BG505 SOSIP.664 gp140; Administered by IM injection; Biological: GLA-LSQ; Administered by IM injection
Placebo Comparator: Part B, Group 5 (P5): Placebo; Participants will receive placebo as one IM injection at Months 0, 2, and 6.	Biological: Placebo; Administered by IM injection
Experimental: Part B, Group 6 (T6): BG505 SOSIP.664 gp140 + Alum; Participants will receive 100 mcg of BG505 SOSIP.664 gp140, admixed with 500 mcg of Alum, administered as one IM injection at Months 0, 2, and 6.	Biological: BG505 SOSIP.664 gp140; Administered by IM injection; Biological: Alum (Aluminum Hydroxide Suspension); Administered by IM injection
Placebo Comparator: Part B, Group 6 (P6): Placebo; Participants will receive placebo as one IM injection at Months 0, 2, and 6.	Biological: Placebo; Administered by IM injection
Experimental: Part C, Group 7 (T7): BG505 SOSIP.664 gp140 + Alum; Participants will receive BG505 SOSIP.664 gp140, 100 mcg admixed with 3M-052-AF, 3 mcg and Alum, 500 mcg to be administered as one 0.5-mL dose intramuscularly (IM) at months 0, 2, and 6.	Biological: BG505 SOSIP.664 gp140; Administered by IM injection; Biological: 3M-052-AF; Administered by IM injection; Biological: Alum (Aluminum Hydroxide Suspension); Administered by IM injection
Placebo Comparator: Part C, Group 7 (P7): Placebo; Participants will receive placebo as one IM injection at Months 0, 2, and 6.	Biological: Placebo; Administered by IM injection
Experimental: Part C, Group 8 (T8): Trimer 4571 + Alum; Participants will receive Trimer 4571, 100 mcg admixed with 3M-052-AF, 5 mcg and Alum, 500 mcg to be administered as one 0.5-mL dose IM at months 0, 2, and 6.	Biological: 3M-052-AF; Administered by IM injection; Biological: Alum (Aluminum Hydroxide Suspension); Administered by IM injection; Biological: Trimer 4571; Administered by IM injection
Placebo Comparator: Part C, Group 8 (P8): Placebo; Participants will receive placebo as one IM injection at Months 0, 2, and 6.	Biological: Placebo; Administered by IM injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of signs and symptoms of local reactogenicity (Part A)	Local symptoms include pain and/or tenderness at the injection site.	Measured for 7 days after each injection
Frequency of signs and symptoms of systemic reactogenicity (Part A)	Systemic symptoms include increased body temperature, malaise and/or fatigue, myalgia, headache, chills, arthralgia, and nausea.	Measured for 7 days after each injection
Frequency of adverse events (AEs) (Part A)	Summarized using Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class and preferred terms	Measured through Month 14
Frequency of expedited AEs (EAEs) (Part A)	Summarized using MedDRA System Organ Class and preferred terms	Measured through Month 14
Frequency of AEs of special interest (AESIs) (Part A)	Summarized using MedDRA System Organ Class and preferred terms	Measured through Month 14
Frequency of signs and symptoms of local reactogenicity (Part B)	Local symptoms include pain and/or tenderness at the injection site.	Measured for 7 days after each injection
Frequency of signs and symptoms of systemic reactogenicity (Part B)	Systemic symptoms include increased body temperature, malaise and/or fatigue, myalgia, headache, chills, arthralgia, and nausea.	Measured for 7 days after each injection
Frequency of AEs (Part B)	Summarized using MedDRA System Organ Class and preferred terms	Measured through Month 18
Frequency of EAEs (Part B)	Summarized using MedDRA System Organ Class and preferred terms	Measured through Month 18
Frequency of AESIs (Part B)	Summarized using MedDRA System Organ Class and preferred terms	Measured through Month 18
Response rate of serum antibody neutralization of autologous (HIV-1 BG505) and other heterologous Tier 2 HIV-1 strains (Part B)	As measured by TZM-bl assay	Measured 2 weeks after the second and third vaccinations (through Month 6.5)
Magnitude of serum antibody neutralization of autologous (HIV-1 BG505) and other heterologous Tier 2 HIV-1 strains (Part B)	As measured by TZM-bl assay	Measured 2 weeks after the second and third vaccinations (through Month 6.5)
Frequency of signs and symptoms of local reactogenicity (Part C)	Local symptoms include pain and/or tenderness at the injection site.	Measured for 7 days after each injection
Frequency of signs and symptoms of systemic reactogenicity (Part C)	Systemic symptoms include increased body temperature, malaise and/or fatigue, myalgia, headache, chills, arthralgia, and nausea.	Measured for 7 days after each injection
Frequency of AEs (Part C)	Summarized using Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class and preferred terms	Measured through Month 18
Frequency of EAEs (Part C)	Summarized using MedDRA System Organ Class and preferred terms	Measured through Month 18
Frequency of AESIs (Part C)	Summarized using MedDRA System Organ Class and preferred terms	Measured through Month 18
Response rate of serum antibody neutralization of autologous (HIV-1 BG505) and other heterologous Tier 2 HIV-1 strains (Part C)	As measured by TZM-bl assay	Measured 2 weeks after the second and third vaccinations (through Month 6.5)
Magnitude of serum antibody neutralization of autologous (HIV-1 BG505) and other heterologous Tier 2 HIV-1 strains (Part C)	As measured by TZM-bl assay	Measured 2 weeks after the second and third vaccinations (through Month 6.5)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate of serum antibody neutralization of autologous (HIV-1 BG505.664) and other heterologous Tier 2 HIV-1 strains (Part A)	As measured by the TZM-bl assay	Measured 2 weeks after the second vaccination (Month 2.5)
Magnitude of serum antibody neutralization of autologous (HIV-1 BG505.664) and other heterologous Tier 2 HIV-1 strains (Part A)	As measured by the TZM-bl assay	Measured 2 weeks after the second vaccination (Month 2.5)
Response rate of serum IgG binding antibodies to BG505 SOSIP.664 gp140 (Part A)	As measured by binding antibody multiplex assay (BAMA)	Measured 2 weeks after the second vaccination (Month 2.5)
Magnitude of serum IgG binding antibodies to BG505 SOSIP.664 gp140 (Part A)	As measured by BAMA	Measured 2 weeks after the second vaccination (Month 2.5)
Response rate of IgG+ B cells binding to BG505 SOSIP.664 gp140 tetramers (Part A)	As measured by multiparameter flow cytometry	Measured 2 weeks after the second vaccination (Month 2.5)
Magnitude of IgG+ B cells binding to BG505 SOSIP.664 gp140 tetramers (Part A)	As measured by multiparameter flow cytometry	Measured 2 weeks after the second vaccination (Month 2.5)
Percent HIV Env-specific CD4+ T cells in blood (Part A)	As measured by multiparameter flow cytometry	Measured 2 weeks post second vaccination (Month 2.5)
Response rate of serum antibody neutralization of autologous (HIV-1 BG505) and other heterologous Tier 2 HIV-1 strains (Part B)	As measured by TZM-bl assay	Measured 6 and 12 months post third vaccination (through Month 18)
Magnitude of serum antibody neutralization of autologous (HIV-1 BG505) and other heterologous Tier 2 HIV-1 strains (Part B)	As measured by TZM-bl assay	Measured 6 and 12 months post third vaccination (through Month 18)
Response rate of IgG binding antibody responses to HIV BG505 SOSIP.664 gp140, and HIV-1 gp120 and gp140 variant strains (to determine off-target non-neutralizing Abs) (Part B)	As measured by BAMA	Measured 2 weeks after the second vaccination and 2 weeks, 6 months, and 12 months after the third vaccination (through Month 18)
Magnitude of IgG binding antibody responses to HIV BG505 SOSIP.664 gp140, and HIV-1 gp120 and gp140 variant strains (to determine off-target non-neutralizing Abs) (Part B)	As measured by BAMA	Measured 2 weeks after the second vaccination and 2 weeks, 6 months, and 12 months after the third vaccination (through Month 18)
Breadth of IgG binding antibody responses to HIV BG505 SOSIP.664 gp140, and HIV-1 gp120 and gp140 variant strains (to determine off-target non-neutralizing Abs) (Part B)	As measured by BAMA	Measured 2 weeks after the second vaccination and 2 weeks, 6 months, and 12 months after the third vaccination (through Month 18)
Response rate of memory IgG+ B cells binding to BG505 SOSIP.664 gp140 tetramers (Part B)	As measured by multiparameter flow cytometry	Measured 2 weeks after the second vaccination and 2 weeks, 6 months, and 12 months after the third vaccination (through Month 18)
Magnitude of memory IgG+ B cells binding to BG505 SOSIP.664 gp140 tetramers (Part B)	As measured by multiparameter flow cytometry	Measured 2 weeks after the second vaccination and 2 weeks, 6 months, and 12 months after the third vaccination (through Month 18)
Response rate of BG505 SOSIP.664 gp140-specific plasmablasts (Part B)	As measured by multiparameter flow cytometry	Measured 1 week after the second and third vaccinations (through Month 6.25)
Magnitude of BG505 SOSIP.664 gp140-specific plasmablasts (Part B)	As measured by multiparameter flow cytometry	Measured 1 week after the second and third vaccinations (through Month 6.25)
Percent HIV Env-specific cytokine-expressing CD4+ T cells in blood (Part B)	Assessed by intracellular cytokine staining (ICS) multiparameter flow cytometry and polyfunctional subset analysis	Measured 2 weeks after the second vaccination and 2 weeks, 6 months, and 12 months after the third vaccination (through Month 18)
Alterations in blood leukocyte populations during the innate response (Part B)	Assessed relative to prevaccine levels (Day 0)	Measured Days 0, 1, 3 and 7
Alterations in RNAseq expression of leukocyte and/or immune cells (Part B)	Assessed through lymphocyte populations, natural killer (NK) cells, dendritic cell (DC) subsets, monocytes subsets, and granulocytes relative to prevaccine levels (Day 0)	Measured Days 0, 1, 3, and 7
Alterations of concentrations of immune cytokines and chemokines (Part B)	Assessed by levels of serum samples relative to prevaccine levels (Day 0)	Measured postvaccination Days 0, 1, 3, 7
Blood cell subpopulation dynamics (Part B)	Assessed by multiparameter flow cytometry, gene expression alterations by RNAseq/transcripts and soluble cytokine/inflammatory mediator alterations comparing day of last vaccination and day of visit for moderate to severe reactogenicity	Measured through Month 18
Response rate of serum antibody neutralization of autologous (HIV-1 BG505) and other heterologous Tier 2 HIV-1 strains (Part C)	As measured by TZM-bl assay	Measured 6 and 12 months post third vaccination (through Month 18)
Magnitude of serum antibody neutralization of autologous (HIV-1 BG505) and other heterologous Tier 2 HIV-1 strains (Part C)	As measured by TZM-bl assay	Measured 6 and 12 months post third vaccination (through Month 18)
Compare the peak and durability of serum binding antibody responses elicited by BG505 SOSIP.664 gp140 adjuvanted with 3 mcg of 3M-052-AF+Alum, and by Trimer 4571 adjuvanted with 5 mcg of 3M-052-AF+Alum with Part B groups		Measured through Month 18
Response rate of IgG binding antibody responses to HIV BG505 SOSIP.664 gp140, and HIV-1 gp120 and gp140 variant strains (to determine off-target non-neutralizing Abs) (Part C)	As measured by BAMA	Measured 2 weeks after the second vaccination and 2 weeks, 6 months, and 12 months after the third vaccination (through Month 18)
Magnitude of IgG binding antibody responses to HIV BG505 SOSIP.664 gp140, and HIV-1 gp120 and gp140 variant strains (to determine off-target non-neutralizing Abs) (Part C)	As measured by BAMA	Measured 2 weeks after the second vaccination and 2 weeks, 6 months, and 12 months after the third vaccination (through Month 18)
Breadth of IgG binding antibody responses to HIV BG505 SOSIP.664 gp140, and HIV-1 gp120 and gp140 variant strains (to determine off-target non-neutralizing Abs) (Part C)	As measured by BAMA	Measured 2 weeks after the second vaccination and 2 weeks, 6 months, and 12 months after the third vaccination (through Month 18)
Compare the peak and durability of BG505 SOSIP.664 gp140-specific B cells elicited by BG505 SOSIP.664 gp140 adjuvanted with 3 mcg of 3M-052-AF+Alum, and by Trimer 4571 adjuvanted with 5 mcg of 3M-052-AF+Alum with Part B groups		Measured through Month 18
Response rate of memory IgG+ B cells binding to BG505 SOSIP.664 gp140 tetramers (Part C)	As measured by multiparameter flow cytometry	Measured 2 weeks after the second vaccination and 2 weeks, 6 months, and 12 months after the third vaccination (through Month 18)
Magnitude of memory IgG+ B cells binding to BG505 SOSIP.664 gp140 tetramers (Part C)	As measured by multiparameter flow cytometry	Measured 2 weeks after the second vaccination and 2 weeks, 6 months, and 12 months after the third vaccination (through Month 18)
Response rate of BG505 SOSIP.664 gp140-specific plasmablasts (Part C)	As measured by multiparameter flow cytometry	Measured 1 week after the second and third vaccinations (through Month 6.25)
Magnitude of BG505 SOSIP.664 gp140-specific plasmablasts (Part C)	As measured by multiparameter flow cytometry	Measured 1 week after the second and third vaccinations (through Month 6.25)
Evaluate Env-specific CD4+ T-helper subpopulations, phenotypes and functions (Part C)		Measured through Month 18
Percent HIV Env-specific cytokine-expressing CD4+ T cells in blood (Part C)	Assessed by intracellular cytokine staining (ICS) multiparameter flow cytometry and polyfunctional subset analysis	Measured 2 weeks after the second vaccination and 2 weeks, 6 months, and 12 months after the third vaccination (through Month 18)
Compare the innate immune responses elicited by BG505 SOSIP.664 gp140 adjuvanted with 3 mcg of 3M-052-AF+Alum, and by Trimer 4571 adjuvanted with 5 mcg of 3M-052-AF+Alum after the first vaccination, and correlate with adaptive immune responses		Measured through Month 18
Alterations in blood leukocyte populations during the innate response (Part C)	Assessed relative to prevaccine levels (Day 0)	Measured Days 0, 1, 3 and 7
Alterations in RNAseq expression of leukocyte and/or immune cells (Part C)	Assessed through lymphocyte populations, natural killer (NK) cells, dendritic cell (DC) subsets, monocytes subsets, and granulocytes relative to prevaccine levels (Day 0)	Measured Days 0, 1, 3, and 7
Alterations of concentrations of immune cytokines and chemokines (Part C)	Assessed by levels of serum samples relative to prevaccine levels (Day 0)	Measured Days 0, 1, 3, and 7
Characterize systemic inflammatory markers among participants with moderate to severe reactogenicity after any vaccination		Measured through Month 18
Blood cell subpopulation dynamics (Part C)	Assessed by multiparameter flow cytometry, gene expression alterations by RNAseq/transcripts and soluble cytokine/inflammatory mediator alterations comparing day of last vaccination and day of visit for moderate to severe reactogenicity	Measured through Month 18

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Fred Hutchinson Cancer Center; International AIDS Vaccine Initiative; HIV Vaccine Trials Network; Dynavax Technologies Corporation; Access to Advanced Health Institute (AAHI)
• Investigators: Study Chair: M. Juliana McElrath, Seattle Vaccine Trials Unit; Study Chair: Nadine Rouphael, Emory University

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2020
• Primary Completion (Estimated): November 4, 2024
• Study Completion (Estimated): November 4, 2024

Study Registration Dates

• First Submitted: November 22, 2019
• First Submitted That Met QC Criteria: November 22, 2019
• First Posted (Actual): November 26, 2019

Study Record Updates

• Last Update Posted (Actual): June 12, 2023
• Last Update Submitted That Met QC Criteria: June 9, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Immunologic Factors; Gastrointestinal Agents; Adjuvants, Immunologic; Antacids; Aluminum Hydroxide; 1018 oligonucleotide; MEDI9197
• Other Study ID Numbers: HVTN 137; 38559 (Registry Identifier: DAIDS-ES Registry Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No