Safety and Immunogenicity of Clade C ALVAC and gp120 HIV Vaccine (HVTN107)

A Phase 1/2a Partially Double-blinded, Randomized Clinical Trial to Characterize the Safety and Immunogenicity of Clade C ALVAC-HIV (vCP2438) and Bivalent Subtype C gp120 Alone, With MF59 Adjuvant, and With Alum Adjuvant in Healthy, HIV-uninfected Adult Participants

The purpose of this study is to evaluate the safety and immune response to an HIV clade C vaccine and to an MF59- or alum-adjuvanted clade C Env protein in healthy, HIV-uninfected adults.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Biological: ALVAC-HIV (vCP2438); Biological: Bivalent Subtype C gp120/MF59; Biological: Bivalent Subtype C gp120 admixed with Al(OH)3 Suspension; Biological: Bivalent Subtype C gp120

Detailed Description

This study will evaluate the safety, tolerability, and immunogenicity to vCP2438 (an HIV clade C vaccine) and to an unadjuvanted or MF59- or alum-adjuvanted bivalent clade C gp120 in healthy, HIV-uninfected adults.

The study will enroll healthy, HIV-uninfected participants aged 18 to 40 years. Participants will be randomly assigned to one of 4 groups. [describe further]

Study visits will include a physical examination, an interview and/or questionnaire, HIV testing and HIV risk-reduction counseling, and urine and blood collection. A subset of participants will provide rectal fluid, cervical fluid, semen, or stool samples.

• Study Type: Interventional
• Enrollment (Actual): 132
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Mozambique
  • Maputo, Mozambique
    • Polana Canico Health Research and Training Center (CISPOC), National Institute of Health (INS) CRS
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 1862
      • Soweto HVTN CRS
    • Johannesburg, Gauteng, South Africa, 1632
      • Aurum Tembisa CRS
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa, 4013
      • eThekwini CRS
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7750
      • Emavundleni CRS
• Zimbabwe
  • Mashonaland East Province
    • Chitungwiza, Mashonaland East Province, Zimbabwe
      • Seke South CRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

General and Demographic Criteria

1. Age of 18 to 40 years
2. Access to a participating HVTN CRS and willingness to be followed for the planned duration of the study
3. Ability and willingness to provide informed consent
4. Assessment of understanding: volunteer demonstrates understanding of this study; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly
5. Agrees not to enroll in another study of an investigational research agent

6. Good general health as shown by medical history, physical exam, and screening laboratory tests

   HIV-Related Criteria:

7. Willingness to receive HIV test results
8. Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling.

9. 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.

   Laboratory Inclusion Values

   Hemogram/Complete blood count (CBC)

10. Hemoglobin ≥ 11.0 g/dL for volunteers who were born female, ≥ 13.0 g/dL for volunteers who were born male
11. White blood cell count = 3,300 to 12,000 cells/mm^3
12. Total lymphocyte count ≥ 800 cells/mm^3
13. Remaining differential either within institutional normal range or with site physician approval

14. Platelets = 125,000 to 550,000/mm^3

    Chemistry

15. Chemistry panel: ALT, AST, and ALP < 1.25 times the institutional upper limit of normal; creatinine ≤ institutional upper limit of normal.

    Virology

16. Negative HIV-1 and -2 blood test: Sites may use locally available assays that have been approved by HVTN Laboratory Operations.
17. Negative Hepatitis B surface antigen (HBsAg)
18. Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV polymerase chain reaction (PCR) if the anti-HCV is positive Urine

19. Normal urine:

    • Negative urine glucose, and
    • 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

20. Volunteers who were born female: negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test performed prior to vaccination on the day of initial vaccination. Persons who are NOT of reproductive potential due to having undergone total hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing.

21. Reproductive status: A volunteer who was born female must:

    • Agree to consistently use effective contraception for sexual activity that could lead to pregnancy from at least 21 days prior to enrollment through the last required protocol clinic visit. Effective contraception is defined as using condoms (male or female), or diaphragm or cervical cap, PLUS 1 of the following methods: Intrauterine device (IUD), Hormonal contraception (in accordance with Republic of South Africa: National Contraception Clinical Guidelines), successful vasectomy in the male partner (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 any other contraceptive method approved by the HVTN 107 Protocol Safety Review Team
    • Or not be of reproductive potential, such as having reached menopause (no menses for 1 year) or having undergone hysterectomy, bilateral oophorectomy, or tubal ligation;
    • Or be sexually abstinent.

22. Volunteers who were born female must also agree not to seek pregnancy through alternative methods, such as artificial insemination or in vitro fertilization until after the last required protocol clinic visit

    Other

23. Volunteers who were born female consenting to provide cervical samples: pap smear within the 3 years prior to enrollment, with the latest result reported as normal or ASCUS (atypical squamous cells of undetermined significance); for those 21 years and older that have not had a pap smear within the last 3 years prior to enrollment, must be willing to undergo a pap smear with the result reported as normal or ASCUS prior to sample collection.

Exclusion Criteria:

General

1. Blood products received within 120 days before first vaccination
2. Investigational research agents received within 30 days before first vaccination
3. Body mass index (BMI) ≥ 40; or BMI ≥ 35 with 2 or more of the following: systolic blood pressure > 140 mm Hg, diastolic blood pressure > 90 mm Hg, current smoker, known hyperlipidemia
4. 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 107 study

5. Pregnant or breastfeeding

   Vaccines and other Injections

6. HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 107 PSRT will determine eligibility on a case-by-case basis.
7. Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine trial. Exceptions may be made for vaccines that have subsequently undergone licensure in a volunteer's country of residence. For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 107 PSRT will determine eligibility on a case-by-case basis. For volunteers who have received an experimental vaccine(s) greater than 5 years ago, eligibility for enrollment will be determined by the HVTN 107 PSRT on a case-by-case basis.
8. Live attenuated vaccines other than influenza vaccine received within 30 days before first vaccination or scheduled within 14 days after injection (eg, measles, mumps, and rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever)
9. Influenza vaccine or any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (eg, tetanus, pneumococcal, Hepatitis A or B)

10. Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination

    Immune System

11. Immunosuppressive medications received within 168 days before first vaccination. (Not exclusionary: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; [3] topical corticosteroids for mild, uncomplicated dermatitis; or [4] a single course of oral/parenteral corticosteroids at doses < 2 mg/kg/day and length of therapy < 11 days with completion at least 30 days prior to enrollment.)
12. Serious adverse reactions to vaccines or to vaccine components such as eggs, egg products, or neomycin, 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 nonanaphylactic adverse reaction to pertussis vaccine as a child.)
13. Immunoglobulin received within 60 days before first vaccination
14. Autoimmune disease

15. Immunodeficiency

    Clinically significant medical conditions

16. Untreated or incompletely treated syphilis infection

17. 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.
18. 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
19. 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.
20. Current anti-tuberculosis (TB) prophylaxis or therapy

21. 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.
22. Diabetes mellitus type 1 or type 2, including cases controlled with diet alone. (Not excluded: history of isolated gestational diabetes.)
23. Thyroidectomy, or thyroid disease requiring medication during the last 12 months

24. 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 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.
25. Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions)
26. 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)
27. 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.
28. Asplenia: any condition resulting in the absence of a functional spleen
29. History of hereditary angioedema, acquired angioedema, or idiopathic angioedema.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1: ALVAC-HIV + gp120/MF59; Participants will receive the ALVAC-HIV (vCP2438) vaccine in the left deltoid at months 0, 1, 3, 6, and 12, and Bivalent Subtype C gp120/MF59 in the right deltoid at months 3, 6, and 12. All injections are via needle and syringe.	Biological: ALVAC-HIV (vCP2438); Expresses the gene products ZM96 gp120 (clade C strain) linked to the sequences encoding the HIV-1 transmembrane (TM) anchor sequence of gp41 (28 amino acids clade B LAI strain) and gag and pro (clade B LAI strain); formulated as a lyophilized vaccine for injection at a viral titer ≥ 1 × 10^6 cell culture infectious dose (CCID)50 and < 1 × 10^8 CCID50 (nominal dose of 10^7 CCID50) and reconstituted with 1mL of sterile sodium chloride solution (NaCl 0.4%) for intramuscular (IM) injection as a single dose; Biological: Bivalent Subtype C gp120/MF59; Consists of 2 subtype C recombinant monomeric proteins, TV1.C gp120 Env and 1086.C gp120 Env, each at a dose of 100 mcg, mixed with MF59 adjuvant (an oil-in-water emulsion); delivered as a 0.5 mL IM injection
Active Comparator: Group 2: ALVAC-HIV + gp120/Al(OH)3; Participants will receive the ALVAC-HIV (vCP2438) vaccine in the left deltoid at months 0, 1, 3, 6, and 12, and Bivalent Subtype C gp120 admixed with Al(OH)3 Suspension in the right deltoid at months 3, 6, and 12. All injections are via needle and syringe.	Biological: ALVAC-HIV (vCP2438); Expresses the gene products ZM96 gp120 (clade C strain) linked to the sequences encoding the HIV-1 transmembrane (TM) anchor sequence of gp41 (28 amino acids clade B LAI strain) and gag and pro (clade B LAI strain); formulated as a lyophilized vaccine for injection at a viral titer ≥ 1 × 10^6 cell culture infectious dose (CCID)50 and < 1 × 10^8 CCID50 (nominal dose of 10^7 CCID50) and reconstituted with 1mL of sterile sodium chloride solution (NaCl 0.4%) for intramuscular (IM) injection as a single dose; Biological: Bivalent Subtype C gp120 admixed with Al(OH)3 Suspension; Consists of 2 subtype C recombinant monomeric proteins, TV1.C gp120 Env and 1086.C gp120 Env, each at a dose of 100 mcg, admixed with Aluminum Hydroxide Suspension (~625 mcg aluminum content); delivered as a 0.5 mL IM injection
Active Comparator: Group 3: ALVAC-HIV + gp120/MF59; Participants will receive the ALVAC-HIV (vCP2438) vaccine in the left deltoid and Bivalent Subtype C gp120/MF59 in the right deltoid at months 0, 1, 6, and 12. All injections are via needle and syringe.	Biological: ALVAC-HIV (vCP2438); Expresses the gene products ZM96 gp120 (clade C strain) linked to the sequences encoding the HIV-1 transmembrane (TM) anchor sequence of gp41 (28 amino acids clade B LAI strain) and gag and pro (clade B LAI strain); formulated as a lyophilized vaccine for injection at a viral titer ≥ 1 × 10^6 cell culture infectious dose (CCID)50 and < 1 × 10^8 CCID50 (nominal dose of 10^7 CCID50) and reconstituted with 1mL of sterile sodium chloride solution (NaCl 0.4%) for intramuscular (IM) injection as a single dose; Biological: Bivalent Subtype C gp120/MF59; Consists of 2 subtype C recombinant monomeric proteins, TV1.C gp120 Env and 1086.C gp120 Env, each at a dose of 100 mcg, mixed with MF59 adjuvant (an oil-in-water emulsion); delivered as a 0.5 mL IM injection
Active Comparator: Group 4: ALVAC-HIV + gp120; Participants will receive the ALVAC-HIV (vCP2438) vaccine in the left deltoid at months 0, 1, 3, 6, and 12, and Bivalent Subtype C gp120 in the right deltoid at months 3, 6, and 12. All injections are via needle and syringe.	Biological: ALVAC-HIV (vCP2438); Expresses the gene products ZM96 gp120 (clade C strain) linked to the sequences encoding the HIV-1 transmembrane (TM) anchor sequence of gp41 (28 amino acids clade B LAI strain) and gag and pro (clade B LAI strain); formulated as a lyophilized vaccine for injection at a viral titer ≥ 1 × 10^6 cell culture infectious dose (CCID)50 and < 1 × 10^8 CCID50 (nominal dose of 10^7 CCID50) and reconstituted with 1mL of sterile sodium chloride solution (NaCl 0.4%) for intramuscular (IM) injection as a single dose; Biological: Bivalent Subtype C gp120; Consists of 2 subtype C recombinant monomeric proteins, TV1.C gp120 Env and 1086.C gp120 Env, each at a dose of 100 mcg, mixed with sodium chloride for injection, 0.9%; delivered as a 0.5 mL IM injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Vaccine-induced Systemic IgG Ab Binding to the 3 gp120 Env Proteins Contained in the Vaccine Regimen (ZM96, TV1.C, and 1086.C) in Group 1 and Group 2	Serum IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:50 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI < 1 is set to 1, and net MFI > 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen > 5,000 MFI, or baseline net MFI > 6,500. Samples from post-enrollment visits have positive responses if they meet three criteria: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of baseline net MFI), (2) net MFI values are greater than 3 times baseline net MFI, and (3) experimental antigen MFI values are greater than 3 times baseline MFI.	Measured at Month 6.5
Level of Vaccine-induced Systemic IgG Ab Binding to the 3 gp120 Env Proteins Contained in the Vaccine Regimen (ZM96, TV1.C, and 1086.C) in Group 1 and Group 2	Serum IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:50 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI < 1 is set to 1, and net MFI > 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen > 5,000 MFI, or baseline net MFI > 6,500. Comparisons were performed among positive responders only (positivity criteria are described in Outcome 1).	Measured at Month 6.5
Occurrence of Vaccine-induced Serum IgA Ab Binding to the 3 gp120 Env Proteins Contained in the Vaccine Regimen (ZM96, TV1.C, and 1086.C) in Group 1 and Group 3	Serum IgA responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:10 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI < 1 is set to 1, and net MFI > 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen > 5,000 MFI, or baseline net MFI > 6,500. Samples from post-enrollment visits have positive responses if they meet three criteria: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of baseline net MFI), (2) net MFI values are greater than 3 times baseline net MFI, and (3) experimental antigen MFI values are greater than 3 times baseline MFI.	Measured at Month 6.5
Level of Vaccine-induced Serum IgA Ab Binding to the 3 gp120 Env Proteins Contained in the Vaccine Regimen (ZM96, TV1.C, and 1086.C) in Group 1 and Group 3	Serum IgA responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:10 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI < 1 is set to 1, and net MFI > 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen > 5,000 MFI, or baseline net MFI > 6,500. Comparisons were performed among positive responders only (positivity criteria are described in Outcome 1).	Measured at Month 6.5
Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Pain and/or Tenderness	Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017]. The maximum grade observed for each symptom over the time frame is presented.	Measured through Month Measured through 3 days after each vaccine dose at Months 0, 1, 3, 6, and 12
Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Erythema and/or Induration	Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017]. The maximum grade observed for each symptom over the time frame is presented.	Measured through Month Measured through 3 days after each vaccine dose at Months 0, 1, 3, 6, and 12
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms	Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017]. The following symptoms are considered as systemic reactogenicity if the onset date was within the periods of assessment specified in the protocol: malaise and/or fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia, and body temperature. The item Max. Systemic Symptoms is the maximum of the individual systemic reactogenicities excluding body temperature for a participant.	Measured through Month Measured through 3 days after each vaccine dose at Months 0, 1, 3, 6, and 12
Number of Participants Reporting Adverse Events (AEs), by Relationship to Study Product	For participants reporting multiple AEs over the time frame, the maximum relationship is counted.	Measured through 30 days after each vaccine dose at Months 0, 1, 3, 6, and 12
Number of Participants Reporting Adverse Events (AEs), by Severity Grade	For participants reporting multiple AEs over the time frame, the maximum severity grade is counted.	Measured through 30 days after each vaccine dose at Months 0, 1, 3, 6, and 12
Number of Participants Reporting Serious Adverse Events (SAEs)	Measured as outlined in Version 2.0 (January 2010) of the Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual).	Measured through Month 18
Number of Participants Reporting Adverse Events of Special Interest (AESIs)	There were no adverse events of special interest reported by any participant.	Measured through Month 18
Chemistry and Hematology Laboratory Measures - ALT (SGPT), AST, Alkaline Phosphatase	For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.	Measured during screening, Days 7, 42, 98, 182, 378, and 455
Chemistry and Hematology Laboratory Measures - Creatinine	For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.	Measured during screening, Days 7, 42, 98, 182, 378, and 455
Chemistry and Hematology Laboratory Measures - Hemoglobin	For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.	Measured during screening, Days 7, 42, 98, 182, 378, and 455
Chemistry and Hematology Laboratory Measures - Lymphocytes, Neutrophils	For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.	Measured during screening, Days 0, 1, 3, 7, 42, 84, 85, 87, 91, 98, 182, 378, and 455
Chemistry and Hematology Laboratory Measures - Platelets, WBC	For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.	Measured during screening, Days 0, 1, 3, 7, 42, 84, 85, 87, 91, 98, 182, 378, and 455
Numbers of Participants With Grade 1 or Higher Local Laboratory Results	The number (percentage) of participants with local laboratory values recorded as meeting Grade 1 AE criteria or above as specified in the DAIDS AE Grading Table were tabulated by treatment arm for each post-vaccination time point.	Measured during screening, Days 0, 1, 3, 7, 42, 84, 85, 87, 91, 98, 182, 378, and 455
Number of Participants With Early Study Termination Associated With an AE or Reactogenicity	There were no early study terminations associated with an AE or reactogenicity reported by any participant.	Measured through Month 18
Number of Participants With Study Product Discontinuation Associated With an AE or Reactogenicity	From the study product discontinuation form, study product discontinuation reasons are tabulated by treatment arm.	Measured through Month 18
Number of Participants Reporting New Chronic Conditions (Requiring Medical Intervention for >= 30 Days)	New chronic conditions are adverse events that require medical intervention for >= 30 days.	Measured through Month 18

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Vaccine-induced Serum IgG Ab Binding to the 3 gp120 Env Proteins Contained in the Vaccine Regimen (ZM96, TV1.C, and 1086.C)	Serum IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:50 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI < 1 is set to 1, and net MFI > 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen > 5,000 MFI, or baseline net MFI > 6,500. Samples from post-enrollment visits have positive responses if they meet three criteria: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of baseline net MFI), (2) net MFI values are greater than 3 times baseline net MFI, and (3) experimental antigen MFI values are greater than 3 times baseline MFI.	Measured at Months 6.5 and 12.
Level of Vaccine-induced Serum IgG Ab Binding to the 3 gp120 Env Proteins Contained in the Vaccine Regimen (ZM96, TV1.C, and 1086.C)	Serum IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:50 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI < 1 is set to 1, and net MFI > 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen > 5,000 MFI, or baseline net MFI > 6,500. Summary was calculated among positive responders only (positivity criteria are described in Outcome 1).	Measured at Months 6.5 and 12.
Occurrence of Vaccine-induced Serum IgG Ab Binding to V2 Env Proteins	Serum IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:50 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI < 1 is set to 1, and net MFI > 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen > 5,000 MFI, or baseline net MFI > 6,500. Samples from post-enrollment visits have positive responses if they meet three criteria: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of baseline net MFI), (2) net MFI values are greater than 3 times baseline net MFI, and (3) experimental antigen MFI values are greater than 3 times baseline MFI.	Measured at Months 6.5 and 12.
Level of Vaccine-induced Serum IgG Ab Binding to V2 Env Proteins	Serum IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:50 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI < 1 is set to 1, and net MFI > 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen > 5,000 MFI, or baseline net MFI > 6,500. Summary was calculated among positive responders only (positivity criteria are described in Outcome 1).	Measured at Months 6.5 and 12.
Vaccine-induced Occurrence of CD4+ T-cells Expressing Markers in Response to HIV Proteins Included in the Vaccine	PBMC samples are stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing markers (IFNg and/or IL-2) after peptide stimulation minus % cells expressing markers after no stimulation. A contingency table is constructed to assess response: stimulation (peptide/none) vs. marker expression (yes/no). A one-sided Fisher's exact test is applied, testing if the number of cells positive for the marker is equal in the stimulated vs. unstimulated cells. A discrete Bonferroni adjustment is made over the peptide pools. Response is positive if adjusted p-value <=0.00001. Any Env magnitude is the maximum of 1086 gp120, TV1 gp120, and Env ZM96 magnitudes. Any HIV magnitude is the sum of Any Env and LAI Gag magnitudes. Data are excluded if blood draw date was outside the visit window, participant was HIV-infected, PBMC viability or T-cell count were low, or negative control was high.	Measured at Months 6.5, 12, 12.5, and 18
Vaccine-induced Percentage of CD4+ T-cells Expressing Markers in Response to HIV Proteins Included in the Vaccine	PBMC samples are stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing markers (IFNg and/or IL-2) after peptide stimulation minus % cells expressing markers after no stimulation. A contingency table is constructed to assess response: stimulation (peptide/none) vs. marker expression (yes/no). A one-sided Fisher's exact test is applied, testing if the number of cells positive for the marker is equal in the stimulated vs. unstimulated cells. A discrete Bonferroni adjustment is made over the peptide pools. Response is positive if adjusted p-value <=0.00001. Any Env magnitude is the maximum of 1086 gp120, TV1 gp120, and Env ZM96 magnitudes. Any HIV magnitude is the sum of Any Env and LAI Gag magnitudes. Data are excluded if blood draw date was outside the visit window, participant was HIV-infected, PBMC viability or T-cell count were low, or negative control was high.	Measured at Months 6.5, 12, 12.5, and 18
Occurrence of Vaccine-induced Serum IgG3 Ab Binding to Env Proteins	Serum IgG3 responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:40 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI < 1 is set to 1, and net MFI > 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen > 5,000 MFI, or baseline net MFI > 6,500. Samples from post-enrollment visits have positive responses if they meet three criteria: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of baseline net MFI), (2) net MFI values are greater than 3 times baseline net MFI, and (3) experimental antigen MFI values are greater than 3 times baseline MFI.	Measured at Months 6.5 and 12.
Level of Vaccine-induced Serum IgG3 Ab Binding to Env Proteins	Serum IgG3 responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:40 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI < 1 is set to 1, and net MFI > 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen > 5,000 MFI, or baseline net MFI > 6,500. Summary was calculated among positive responders only (positivity criteria are described in Outcome 1).	Measured at Months 6.5 and 12.
Occurrence of Vaccine-induced Serum IgA Ab Binding to Env Proteins	Serum IgA responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:10 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI < 1 is set to 1, and net MFI > 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen > 5,000 MFI, or baseline net MFI > 6,500. Samples from post-enrollment visits have positive responses if they meet three criteria: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of baseline net MFI), (2) net MFI values are greater than 3 times baseline net MFI, and (3) experimental antigen MFI values are greater than 3 times baseline MFI.	Measured at Months 6.5 and 12.
Level of Vaccine-induced Serum IgA Ab Binding to Env Proteins	Serum IgA responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:10 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI < 1 is set to 1, and net MFI > 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen > 5,000 MFI, or baseline net MFI > 6,500. Summary was calculated among positive responders only (positivity criteria are described in Outcome 1).	Measured at Months 6.5 and 12.
Occurrence of Vaccine-induced Serum IgG Ab Binding to the 3 gp120 Env Proteins Contained in the Vaccine Regimen (ZM96, TV1.C, and 1086.C)	Serum IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:50 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI < 1 is set to 1, and net MFI > 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen > 5,000 MFI, or baseline net MFI > 6,500. Samples from post-enrollment visits have positive responses if they meet three criteria: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of baseline net MFI), (2) net MFI values are greater than 3 times baseline net MFI, and (3) experimental antigen MFI values are greater than 3 times baseline MFI.	Measured at Months 12.5 and 18.
Level of Vaccine-induced Serum IgG Ab Binding to the 3 gp120 Env Proteins Contained in the Vaccine Regimen (ZM96, TV1.C, and 1086.C)	Serum IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:50 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI < 1 is set to 1, and net MFI > 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen > 5,000 MFI, or baseline net MFI > 6,500. Summary was calculated among positive responders only (positivity criteria are described in Outcome 1).	Measured at Months 12.5 and 18.
Occurrence of Vaccine-induced Serum IgG Ab Binding to V2 Env Proteins	Serum IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:50 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI < 1 is set to 1, and net MFI > 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen > 5,000 MFI, or baseline net MFI > 6,500. Samples from post-enrollment visits have positive responses if they meet three criteria: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of baseline net MFI), (2) net MFI values are greater than 3 times baseline net MFI, and (3) experimental antigen MFI values are greater than 3 times baseline MFI.	Measured at Months 12.5 and 18.
Level of Vaccine-induced Serum IgG Ab Binding to V2 Env Proteins	Serum IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:50 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI < 1 is set to 1, and net MFI > 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen > 5,000 MFI, or baseline net MFI > 6,500. Summary was calculated among positive responders only (positivity criteria are described in Outcome 1).	Measured at Months 12.5 and 18.
Occurrence of Vaccine-induced Serum IgG3 Ab Binding to Env Proteins	Serum IgG3 responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:40 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI < 1 is set to 1, and net MFI > 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen > 5,000 MFI, or baseline net MFI > 6,500. Samples from post-enrollment visits have positive responses if they meet three criteria: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of baseline net MFI), (2) net MFI values are greater than 3 times baseline net MFI, and (3) experimental antigen MFI values are greater than 3 times baseline MFI.	Measured at Months 12.5 and 18.
Level of Vaccine-induced Serum IgG3 Ab Binding to Env Proteins	Serum IgG3 responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:40 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI < 1 is set to 1, and net MFI > 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen > 5,000 MFI, or baseline net MFI > 6,500. Summary was calculated among positive responders only (positivity criteria are described in Outcome 1).	Measured at Months 12.5 and 18.
HIV-specific CD4+ T Cell Polyfunctionality by ICS - Functionality Scores	COMPASS uses a Bayesian hierarchical framework to model all observed functional cell subsets and select those most likely to exhibit antigen-specific responses. Cell-subset responses are quantified by posterior probabilities. The functionality score (FS) summarizes, as a single number for each participant, the proportion of antigen-specific cell subsets among all measured subsets, irrespective of degree of functionality. FS ranges from zero to one. FS will assign a higher score to participants that exhibit antigen specificity in more cell subsets irrespective of their degree of functionality.	Measured at Months 6.5, 12, 12.5, and 18
HIV-specific CD4+ T Cell Polyfunctionality by ICS - Polyfunctionality Scores	COMPASS uses a Bayesian hierarchical framework to model all observed functional cell subsets and select those most likely to exhibit antigen-specific responses. Cell-subset responses are quantified by posterior probabilities. The polyfunctionality score (PFS) summarizes, as a single number for each participant, the proportion of antigen-specific cell subsets among all measured subsets, weighted by the degree of functionality of the corresponding subset. PFS ranges from zero to one. PFS will assign a higher score to participants with antigen-specific cell subsets of higher degree.	Measured at Months 6.5, 12, 12.5, and 18

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: GlaxoSmithKline; Sanofi Pasteur, a Sanofi Company; HIV Vaccine Trials Network
• Investigators: Study Chair: Kathy Mngadi, Centre for the AIDS Programme of Research in South Africa; Study Chair: Paul Goepfert, University of Alabama at Birmingham

Publications and helpful links

General Publications

• Moodie Z, Li SS, Giorgi EE, Williams LD, Dintwe O, Carpp LN, Chen S, Seaton KE, Sawant SS, Zhang L, Heptinstall J, Liu S, Grunenberg N, Tomaka F, Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Ake JA, Vasan S, Pantaleo G, Frank I, Baden LR, Goepfert PA, Keefer M, Chirenje M, Hosseinipour MC, Mngadi K, Laher F, Garrett N, Bekker LG, De Rosa S, Andersen-Nissen E, Kublin JG, Lu S, Gilbert PB, Gray GE, Corey L, McElrath MJ, Tomaras GD. A polyvalent DNA prime with matched polyvalent protein/GLA-SE boost regimen elicited the most robust and broad IgG and IgG3 V1V2 binding antibody and CD4+ T cell responses among 13 HIV vaccine trials. Emerg Microbes Infect. 2025 Dec;14(1):2485317. doi: 10.1080/22221751.2025.2485317. Epub 2025 Apr 7.
• Moodie Z, Andersen-Nissen E, Grunenberg N, Dintwe OB, Omar FL, Kee JJ, Bekker LG, Laher F, Naicker N, Jani I, Mgodi NM, Hunidzarira P, Sebe M, Miner MD, Polakowski L, Ramirez S, Nebergall M, Takuva S, Sikhosana L, Heptinstall J, Seaton KE, De Rosa S, Diazgranados CA, Koutsoukos M, Van Der Meeren O, Barnett SW, Kanesa-Thasan N, Kublin JG, Tomaras GD, McElrath MJ, Corey L, Mngadi K, Goepfert P; HVTN 107 Protocol Team. Safety and immunogenicity of a subtype C ALVAC-HIV (vCP2438) vaccine prime plus bivalent subtype C gp120 vaccine boost adjuvanted with MF59 or alum in healthy adults without HIV (HVTN 107): A phase 1/2a randomized trial. PLoS Med. 2024 Mar 19;21(3):e1004360. doi: 10.1371/journal.pmed.1004360. eCollection 2024 Mar.

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2017
• Primary Completion (Actual): December 12, 2019
• Study Completion (Actual): December 12, 2019

Study Registration Dates

• First Submitted: September 13, 2017
• First Submitted That Met QC Criteria: September 13, 2017
• First Posted (Actual): September 15, 2017

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: HIV
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; HIV Infections; AIDSVAX
• Other Study ID Numbers: HVTN 107

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
• product manufactured in and exported from the U.S.: Yes