Safety of and Immune Response to Vaccination With 2 Experimental HIV Vaccines in Healthy Adults

NCT02109354 | Completed Phase 1 DMC

• 1 other identifier: HVTN 097
• Study Type: interventional
• Target: 202
• Locations: 1 country
• Sites: 3

Brief Summary

The HIV Vaccine Trials Network (HVTN) is doing a study to test 2 experimental HIV vaccines in combination with 2 licensed vaccines for tetanus and hepatitis B. HIV is the virus that causes AIDS. Tetanus is an infection that causes muscular spasms. Hepatitis B is a virus that can cause liver failure. About 100 people will take part in this study at multiple sites. The US National Institutes of Health (NIH) is paying for the study. We are doing this study to answer several questions.

• Are the HIV study vaccines safe to give to people?
• Are people able to take the HIV study vaccines without becoming too uncomfortable?
• How do people's immune systems respond to the HIV study vaccines? (Your immune system protects you from disease.)
• Can people's immune responses to a tetanus or hepatitis B vaccines help us understand how their immune systems might respond to the HIV study vaccines?
• Is there a common immune response to licensed vaccines like the tetanus and hepatitis B vaccines?

Conditions

HIV Infection

Keywords

HIV infection; Vaccine

Outcome Measures

Primary Outcomes (10)

• Frequency of local and systemic reactogenicity signs and symptoms, laboratory measures of safety, and a line listing of all AEs meeting DAIDS criteria for expedited reporting.

  13.5 months

• HIV-specific total IgG and IgA binding antibody responses as assessed by multiplex assay

  2 weeks following the final vaccination of ALVAC-HIV + AIDSVAX B/E.

• Neutralizing antibody magnitude and breadth against tier 1 and tier 2 HIV-1 isolates as assessed by area under the magnitude-breadth curves

  2 weeks following the final vaccination of ALVAC-HIV + AIDSVAX B/E.

• Magnitude and frequency of HIV-specific CD4+ and CD8+ T-cell responses as assessed by flow cytometry at 2 weeks following the final vaccination of ALVACHIV + AIDSVAX B/E.

  2 weeks post final vaccination of ALVACHIV + AIDSVAX B/E

• Frequency of severe local and systemic reactogenicity signs and symptoms (pain, tenderness, erythema, induration, fever, malaise/fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia)

  3 days after each vaccine dose

• Frequency of AEs by body system, Medical Dictionary for Regulatory Activities (MedDRA) preferred term, severity, and assessed relationship to study products

  30 days after each vaccine dose

• Frequency of SAEs, adverse events of special interest (AESIs; Appendix K), and new chronic conditions (requiring medical intervention for ≥ 30 days) throughout the study

  19.5 months

• Composite of safety laboratory measures: white blood cells, neutrophils, lymphocytes, hemoglobin, platelets, alanine aminotransferase, aspartate aminotransferase, alkaline phosphate, and creatinine at baseline and following vaccinations

  19.5 months

• Frequency of AEs leading to early participant withdrawal or early discontinuation of study products administration throughout the study.

  19.5 months

• Occurrence and level of vaccine-induced IgG binding Ab to gp120 and V1V2 scaffold

  2 week sand 6 months post first-boost

Secondary Outcomes (18)

• Anti-V1/V2 IgG binding antibody responses as assessed by multiplex assay

  2 weeks following the final vaccination of ALVAC-HIV + AIDSVAX B/E

• Titers of antibody-dependent cellular cytotoxicity (ADCC) or antibody-dependent cellular viral inhibition (ADCVI)-mediating antibodies

  2 weeks following the final vaccination of ALVAC-HIV + AIDSVAX B/E.

• HIV-specific IgG subclass (IgG1-IgG4) characterization as determined by HIV-1 multiplex Ab assay

  2 weeks following the final vaccination of ALVAC-HIV + AIDSVAX B/E.

• Avidity indices for Env-specific antibodies

  2 weeks following the final vaccination of ALVAC-HIV + AIDSVAX B/E.

• HIV-capturing non-neutralizing antibodies as assessed by competitive virus capture assay

  2 weeks following the final vaccination of ALVAC-HIV + AIDSVAX B/E.

Study Arms (3)

HIV Regimen + Tetanus and HBV Vaccines

ACTIVE COMPARATOR

Participants will receive a tetanus vaccine injection (tetanus toxoid vaccine), followed by 2 injection of an experimental canarypox HIV vaccine (ALVAC-HIV; months 1, 2), than 2 injection of a protein HIV vaccine boost (AIDSVAX B/E; months 4, 7), followed by a hepatitis B vaccine series (months 7.5, 8.5, 13)

Biological: ALVAC-HIV; Biological: AIDSVAX B/E; Biological: Hepatitis B vaccine; Biological: Tetanus toxoid vaccine

HIV Vaccine Regimen

ACTIVE COMPARATOR

Participants will receive a placebo for tetanus vaccine by injection (placebo tetanus toxoid vaccine), followed by 2 injection of an experimental canarypox HIV vaccine (ALVAC-HIV; months 1, 2), than 2 injection of a protein HIV vaccine boost (AIDSVAX B/E; months 4, 7), followed by a placebo for hepatitis B vaccine series (months 7.5, 8.5, 13)

Biological: ALVAC-HIV; Biological: AIDSVAX B/E; Biological: Placebo for hepatitis B vaccine; Biological: Placebo for tetanus vaccine

Tetanus and HBV Vaccines

PLACEBO COMPARATOR

Participants will receive a tetanus vaccine injection (tetanus toxoid vaccine), followed by 2 injection of a placebo for the experimental canarypox HIV vaccine (placebo for ALVAC-HIV; months 1, 2), than 2 injection of a placebo protein HIV vaccine boost (placebo for AIDSVAX B/E; months 4, 7), followed by a hepatitis B vaccine series (months 7.5, 8.5, 13)

Biological: Placebo for ALVAC-HIV; Biological: Placebo for AIDSVAX B/E; Biological: Hepatitis B vaccine; Biological: Tetanus toxoid vaccine

Interventions

ALVAC-HIV BIOLOGICAL

Formulated as a lyophilized vaccine for injection and is reconstituted with 1.05 mL of sterile Sodium Chloride solution (0.4% NaCl) for a single 1 mL dose of \>1.0 x 106 CCID50/mL, to administer intramuscularly (IM).

Also known as: vCP1521

HIV Regimen + Tetanus and HBV Vaccines; HIV Vaccine Regimen

AIDSVAX B/E BIOLOGICAL

300 mcg of subtype B (MN) HIV gp120 glycoprotein and 300 mcg of subtype E (A244) HIV gp120 glycoprotein adsorbed onto 600 mcg of aluminum hydroxide gel adjuvant. Each vial contains 1.2 mL of sterile suspension, to administer 1 mL IM.

Also known as: gp120

HIV Regimen + Tetanus and HBV Vaccines; HIV Vaccine Regimen

Placebo for ALVAC-HIV BIOLOGICAL

A sterile, lyophilized product that consists of a mixture of virus stabilizer, and freeze drying medium and is reconstituted with 1.05 mL of sterile Sodium Chloride (0.4% NaCl) for a single 1 mL dose, to administer IM.

Tetanus and HBV Vaccines

Placebo for AIDSVAX B/E BIOLOGICAL

Sodium Chloride for Injection, 0.9% administered IM.

Tetanus and HBV Vaccines

Hepatitis B vaccine BIOLOGICAL

Each 1 mL dose contains 20 mcg of hepatitis B surface antigen (HBsAg) adsorbed onto 500 mcg aluminum as aluminum hydroxide, to administer IM.

Also known as: HBV vaccine, ENGERIX-B

HIV Regimen + Tetanus and HBV Vaccines; Tetanus and HBV Vaccines

Tetanus toxoid vaccine BIOLOGICAL

The active ingredient is tetanus toxoid (≥ 40 I.U. / 0.5 mL) adsorbed on aluminium hydroxide dihydrate (600 mcg of aluminium), to administer IM.

Also known as: Tetanus vaccine, Tetavax

HIV Regimen + Tetanus and HBV Vaccines; Tetanus and HBV Vaccines

Placebo for hepatitis B vaccine BIOLOGICAL

Sodium Chloride for Injection, 0.9% administered IM.

HIV Vaccine Regimen

Placebo for tetanus vaccine BIOLOGICAL

Sodium Chloride for Injection, 0.9% administered IM.

HIV Vaccine Regimen

Eligibility Criteria

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

You may qualify if:

• 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
• Willingness to receive tetanus and Hepatitis B vaccination
• Willingness to receive HIV test results
• Willingness to discuss HIV infection risks, amenable to HIV risk reduction counseling, and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit
• Assessed by the clinic staff as being at "low risk" for HIV infection
• 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/mm3
• Total lymphocyte count ≥ 800 cells/mm3
• Remaining differential either within institutional normal range or with site physician approval
• Platelets = 125,000 to 550,000/mm3

You may not qualify if:

• 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 during the planned duration of the HVTN 097 study
• Pregnant, breastfeeding or lactating
• History of Hepatitis B viral infection
• History of tetanus disease 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 097 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 by the South Africa Medicines Control Council (MCC). For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 097 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 097 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, pneumococcal, Hepatitis A)
• Any requirement to receive an HBV vaccine other than the HBV vaccine given during the study period.
• Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination
• Known to have received a tetanus vaccination within the last 5 years prior to first vaccination.
• Immunosuppressive medications received within 168 days before first vaccination. (Not excluded: \[1\] 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.

Sponsors & Collaborators

• HIV Vaccine Trials Network: lead

Study Sites (3)

Emavundleni Desmond Tutu HIV Centre CRS

Cape Town, Western Cape, 7750, South Africa

Location

Aurum Institute for Health Research

Klerksdorp, 2570, South Africa

Location

Perinatal HIV Research Unit

Soweto, 2013, South Africa

Location

Related Publications (3)

• 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

• Zhao LP, Fiore-Gartland A, Carpp LN, Cohen KW, Rouphael N, Fleurs L, Dintwe O, Zhao M, Moodie Z, Fong Y, Garrett N, Huang Y, Innes C, Janes HE, Lazarus E, Michael NL, Nitayaphan S, Pitisuttithum P, Rerks-Ngarm S, Robb ML, De Rosa SC, Corey L, Gray GE, Seaton KE, Yates NL, McElrath MJ, Frahm N, Tomaras GD, Gilbert PB. Landscapes of binding antibody and T-cell responses to pox-protein HIV vaccines in Thais and South Africans. PLoS One. 2020 Jan 30;15(1):e0226803. doi: 10.1371/journal.pone.0226803. eCollection 2020.

  PMID: 31999736 DERIVED

• Lazarus EM, Otwombe K, Adonis T, Sebastian E, Gray G, Grunenberg N, Roux S, Churchyard G, Innes C, Laher F. Uptake of genital mucosal sampling in HVTN 097, a phase 1b HIV vaccine trial in South Africa. PLoS One. 2014 Nov 17;9(11):e112303. doi: 10.1371/journal.pone.0112303. eCollection 2014.

  PMID: 25401780 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

AIDSVAX; AIDSVAX B-E; HIV Envelope Protein gp120; Hepatitis B Vaccines; Engerix-B; Tetanus Toxoid

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

Intervention Hierarchy (Ancestors)

HIV Antigens; Antigens, Viral; Viral Proteins; Proteins; Amino Acids, Peptides, and Proteins; env Gene Products, Human Immunodeficiency Virus; Gene Products, env; Retroviridae Proteins; Human Immunodeficiency Virus Proteins; Viral Envelope Proteins; Viral Structural Proteins; Antigens; Biological Factors; Viral Hepatitis Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Toxoids

Study Officials

• Glenda Gray, MD

  Perinatal HIV Research Unit

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: December 12, 2013
• First Posted: April 9, 2014
• Study Start: June 18, 2013
• Primary Completion: February 2, 2015
• Study Completion: February 2, 2015
• Last Updated: June 21, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (3)