Safety and Immunogenicity of Clade C ALVAC and gp120 HIV Vaccine

NCT03284710 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: HVTN 107
• Study Type: interventional
• Target: 132
• Locations: 3 countries
• Sites: 6

Brief Summary

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.

Conditions

HIV Infections

Keywords

HIV

Outcome Measures

Primary Outcomes (20)

• 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

• 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

• 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

Secondary Outcomes (18)

• 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)

  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)

  Measured at Months 6.5 and 12.

• Occurrence of Vaccine-induced Serum IgG Ab Binding to V2 Env Proteins

  Measured at Months 6.5 and 12.

• Level of Vaccine-induced Serum IgG Ab Binding to V2 Env Proteins

  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

  Measured at Months 6.5, 12, 12.5, and 18

Study Arms (4)

Group 1: ALVAC-HIV + gp120/MF59

ACTIVE COMPARATOR

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); Biological: Bivalent Subtype C gp120/MF59

Group 2: ALVAC-HIV + gp120/Al(OH)3

ACTIVE COMPARATOR

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); Biological: Bivalent Subtype C gp120 admixed with Al(OH)3 Suspension

Group 3: ALVAC-HIV + gp120/MF59

ACTIVE COMPARATOR

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); Biological: Bivalent Subtype C gp120/MF59

Group 4: ALVAC-HIV + gp120

ACTIVE COMPARATOR

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); Biological: Bivalent Subtype C gp120

Interventions

ALVAC-HIV (vCP2438) BIOLOGICAL

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

Group 1: ALVAC-HIV + gp120/MF59; Group 2: ALVAC-HIV + gp120/Al(OH)3; Group 3: ALVAC-HIV + gp120/MF59; Group 4: ALVAC-HIV + gp120

Bivalent Subtype C gp120/MF59 BIOLOGICAL

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

Group 1: ALVAC-HIV + gp120/MF59; Group 3: ALVAC-HIV + gp120/MF59

Bivalent Subtype C gp120 admixed with Al(OH)3 Suspension BIOLOGICAL

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

Group 2: ALVAC-HIV + gp120/Al(OH)3

Bivalent Subtype C gp120 BIOLOGICAL

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

Group 4: ALVAC-HIV + gp120

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• General and Demographic Criteria
• Age of 18 to 40 years
• Access to a participating HVTN 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 study; 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
• 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.
• Hemogram/Complete blood count (CBC)
• Hemoglobin ≥ 11.0 g/dL for volunteers who were born female, ≥ 13.0 g/dL for volunteers who were born male
• White blood cell count = 3,300 to 12,000 cells/mm\^3
• Total lymphocyte count ≥ 800 cells/mm\^3

You may not qualify if:

• 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: 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 107 study
• Pregnant or breastfeeding
• 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 107 PSRT will determine eligibility on a case-by-case basis.
• 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.
• 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)
• 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)
• Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination
• Immune System
• 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.)
• Immunoglobulin received within 60 days before first vaccination

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• HIV Vaccine Trials Network: collaborator
• Sanofi Pasteur, a Sanofi Company: collaborator
• GlaxoSmithKline: collaborator

Study Sites (6)

Polana Canico Health Research and Training Center (CISPOC), National Institute of Health (INS) CRS

Maputo, Mozambique

Location

Aurum Tembisa CRS

Johannesburg, Gauteng, 1632, South Africa

Location

Soweto HVTN CRS

Johannesburg, Gauteng, 1862, South Africa

Location

eThekwini CRS

Durban, KwaZulu-Natal, 4013, South Africa

Location

Emavundleni CRS

Cape Town, Western Cape, 7750, South Africa

Location

Seke South CRS

Chitungwiza, Mashonaland East Province, Zimbabwe

Location

Related Publications (2)

• 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.

  PMID: 40190112 DERIVED

• 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.

  PMID: 38502656 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

AIDSVAX

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Yunda Huang, PhD, Multiple Principal Investigator, HVTN Statistical and Data Management Center
• Organization: Fred Hutchinson Cancer Center

hvtn.covpn.sdmc@hvtn.org

206-667-5780

Study Officials

• Paul Goepfert

  University of Alabama at Birmingham

  STUDY CHAIR

• Kathy Mngadi

  Centre for the AIDS Programme of Research in South Africa

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2017
• First Posted: September 15, 2017
• Study Start: June 19, 2017
• Primary Completion: December 12, 2019
• Study Completion: December 12, 2019
• Last Updated: May 4, 2026
• Results First Posted: February 18, 2021

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

MO (1); ZA (4); ZI (1)