Evaluating the Safety and Immunogenicity of Polyvalent DNA and Recombinant gp120 Protein HIV Vaccine (PDPHV) in Healthy, HIV-uninfected Adults

Phase 2a Clinical Trial to Evaluate the Safety and Immunogenicity of Polyvalent Env (A, B, C, A/E) / Gag (C) DNA and gp120 (A, B, C, A/E) Protein HIV-1 Vaccines (PDPHV) With Either Alhydrogel or GLA-SE in Healthy Adults Living Without HIV

The purpose of the study is to evaluate the safety, tolerability, and immunogenicity of polyvalent env (A,B,C,A/E)/gag (C) DNA prime and gp120 (A,B,C,A/E) protein HIV-1 vaccines boost (PDPHV) with either Alhydrogel or GLA-SE in healthy, HIV-uninfected adults.

Volunteers will receive either the PDPHV or the placebo (normal saline) by intramuscular injections. Some volunteers will receive Alhydrogel and others will receive GLA-SE as part of the protein boost.

Study Overview

• Status: Not yet recruiting
• Conditions: HIV Prevention
• Intervention / Treatment: Biological: PDPHV Recombinant Protein Vaccines (gp120 (A, B, C, A/E)); Biological: Alhydrogel adjuvant; Biological: Placebo for DNA Vaccines, Protein Vaccines and Adjuvants; Biological: PDPHV Plasmid DNA Vaccines (env (A, B, C, A/E)/gag (C)); Biological: GLA-SE adjuvant

Detailed Description

Participants will be enrolled in Group 1 to group 5. Within each group, participants will be randomly assigned to either Treatment or Placebo Control.

Group 1 (Sentinel group) will be enrolled first to test the safety of the protein vaccines mixed with the Alhydrogel adjuvant. Participants in Group 1 (Treatment) will receive polyvalent gp120 (A, B, C, A/E) protein vaccines mixed with Alhydrogel in the non-dominant arm at months 0, and 3. Participants in Group 1 (Control) will receive placebo at months 0, and 3.

The Safety Monitoring Board (SMB) will evaluate the safety profile of volunteers in Group 1 in two weeks after the 2nd dose. The Alhydrogel adjuvanted Protein Vaccines boosts in group 2 and group 4 can only proceed after SMB reviews the safety data from Group 1 and approves to the use of Alhydrogel in these studies.

Participants in Group 2 (Treatment) will receive env (A, B, C, A/E)/gag (C) DNA Vaccines in the dominant arm at months 0, and 1, followed by gp120 (A, B, C, A/E) Protein Vaccines mixed with Alhydrogel boosts in the non-dominant arm at Months 3, and 6. Participants in Group 2 (Control) will receive placebo at Months 0, 1, 3, and 6.

Participants in Group 3 (Treatment) will receive env (A, B, C, A/E)/gag (C) DNA Vaccines in the dominant arm at months 0, and 1, followed by gp120 (A, B, C, A/E) Protein Vaccines mixed with GLA-SE boosts in the non-dominant arm at Months 3, and 6. Participants in Group 3 (Control) will receive placebo at Months 0, 1, 3, and 6.

Participants in Group 4 (Treatment) will receive env (A, B, C, A/E)/gag (C) DNA Vaccines in the dominant arm at months 0, and 1, followed by gp120 (A, B, C, A/E) Protein Vaccines mixed with Alhydrogel boosts in the non-dominant arm AND env (A, B, C, A/E)/gag (C) DNA Vaccines in the dominant arm at Months 3, and 6. Participants in Group 4 (Control) will receive placebo at Months 0, 1, 3, and 6.

Participants in Group 5 (Treatment) will receive env (A, B, C, A/E)/gag (C) DNA Vaccines in the dominant arm at months 0, and 1, followed by gp120 (A, B, C, A/E) Protein Vaccines mixed with GLA-SE boosts in the non-dominant arm AND env (A, B, C, A/E)/gag (C) DNA Vaccines in the dominant arm at Months 3, and 6. Participants in Group 5 (Control) will receive placebo at Months 0, 1, 3, and 6.

Study visits for participants in Group 1 will occur at Months 0, 0.5, 3, 3.5, 6, 9, and 15. Study visits for participants in Group 2 to Group 5 will occur at Monthes 0, 0.5, 1, 1.5, 3, 3.5, 6, 6.5, 12 and 18. Visits may include physical examination, blood and urine collection, HIV testing, risk reduction counselling, and questionnaires.

• Study Type: Interventional
• Enrollment (Estimated): 126
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Project manager; Phone Number: 508-282-9447; Email: WHV.doc@whvaccine.com

Study Locations

• South Africa
  • Cape Town, South Africa
    • Emavundleni Clinical Research Site, Desmond Tutu Health Foundation
    • Principal Investigator: Conasagrie Nair
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
      • Principal Investigator: Stephen Walsh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age of 18 to 55 years
2. Access to a trial site and willingness to be followed for the planned duration of the study.
3. Ability and willingness to provide informed consent
4. Demonstrates an understanding of the study
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
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.
10. Hemoglobin ≥ 11.0 g/dL for volunteers who were born female, ≥ 12.0 g/dL for volunteers who were born male
11. White blood cell count = 3,000 to 12,000 cells/mm3
12. Total lymphocyte count > 800 cells/mm3
13. Remaining differential either within institutional normal range or with site physician approval
14. Platelets = 125,000 to 450,000/mm3
15. Chemistry panel: ALT< 1.25 times the institutional upper limit of normal; creatinine < 1.1 times institutional upper limit of normal.
16. Negative HIV-1 and -2 blood test
17. Negative Hepatitis B surface antigen (HBsAg)
18. Negative anti-Hepatitis C virus antibodies (anti-HCV)

19. Urinalysis

    • Negative or trace urine glucose, and
    • Negative or trace urine protein, and
    • Negative, trace, or 1+ urine hemoglobin (if 1+ hemoglobin is present on dipstick in the absence of menstruation, a microscopic urinalysis with red blood cells morphology within institutional normal range)
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.

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 until at least 3 months after last vaccination.;
    • 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 (verified by medical records where available, or based on the judgement of the local investigator);
    • Or have no male sexual partner.
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 at least 3 months after last vaccination.

Exclusion Criteria:

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.
4. Intent to participate in another study of an investigational research agent or any other study that requires HIV antibody testing.
5. Pregnant or breastfeeding.
6. Active duty and reserve US military personnel.
7. HIV vaccine(s) received in a prior HIV vaccine trial.
8. Non-HIV experimental vaccine(s) received within the last 1 year in a prior vaccine trial unless the vaccine subsequently received regulatory approval or emergency authorization.
9. Live attenuated vaccines, other than the influenza vaccine, received within 30 days before first vaccination or scheduled within 14 days after injection.
10. Any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination.
11. Allergy treatment with antigen injections within 30 days before the first vaccination or those that are scheduled within 14 days after the first vaccination
12. Immunosuppressive medications received within 168 days before the first vaccination.
13. Serious adverse reactions to vaccines or to vaccine components, including a history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain.
14. Immunoglobulin received within 60 days before the first vaccination.
15. Autoimmune disease, connective tissue disease, or history of vasculitis. A volunteer with a history of a potential immune-mediated medical condition (PIMMC), either active or remote. Not exclusionary: (1) remote history of Bell's palsy (>2 years ago) not associated with other neurologic symptoms; (2) mild psoriasis or other mild, uncomplicated, localized or dermatologic condition that does not require ongoing systemic treatment; (3) remote history (>10 years ago) of Kawasaki disease without sequelae; and (4) celiac disease well controlled for 6 months with diet only.
16. Immunodeficiency.
17. Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health as per the investigator's judgement.
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
22. Diabetes mellitus type 1 or type 2, including cases controlled with diet alone. (Not excluded: history of isolated gestational diabetes.)
23. Uncontrolled thyroid disease, recent thyroidectomy, or new onset hypothyroidism or hyperthyroidism, defined as new or changing doses of thyroid medication within 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 (defined as ≥ 90 mmHg diastolic or ≥ 140 mmHg systolic after 10 minutes' rest).
    • If a person has NOT been found to have elevated blood pressure or hypertension during screening or previously, exclude for systolic blood pressure ≥ 140 mm Hg at enrollment or diastolic blood pressure ≥ 90 mm Hg at enrollment. One repeat attempt at measurement on a different date is allowed.
25. Bleeding disorder diagnosed by a doctor.
26. Malignancy.
27. Seizure disorder: History of seizure(s) within past three 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: Quadruple

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 (Treatment): Protein Vaccines/Alhydrogel; Participants will receive 400 mcg Recombinant Protein Vaccines admixed with 800 mcg Alhydrogel adjuvant to be administered as a 1 mL (IM) injection in the deltoid of the NON-DOMINANT arm at months 0 and 3.	Biological: PDPHV Recombinant Protein Vaccines (gp120 (A, B, C, A/E)); The Recombinant Protein Vaccines (gp120 (A, B, C, A/E)) contains equal amounts of 4 gp120 proteins.; Biological: Alhydrogel adjuvant; PDPHV protein vaccines adjuvant
Placebo Comparator: Group 1 (Control); Participants will receive Placebo to be administered as a 1 mL (IM) injection in the deltoid of the NON-DOMINANT arm at months 3 and 6.	Biological: Placebo for DNA Vaccines, Protein Vaccines and Adjuvants; Sodium Chloride for Injection, USP 0.9%.
Experimental: Group 2 (Treatment): DNA Vaccines prime, Protein Vaccines/Alhydrogel boost; Participants will receive 2000 mcg Plasmid DNA Vaccines to be administered as a 0.8 mL (IM) injection in the deltoid of the DOMINANT arm at months 0 and 1; and 400 mcg Recombinant Protein Vaccines admixed with 800 mcg Alhydrogel, to be administered as a 1 mL (IM) injection in the deltoid of the NON-DOMINANT arm at months 3 and 6.	Biological: PDPHV Recombinant Protein Vaccines (gp120 (A, B, C, A/E)); The Recombinant Protein Vaccines (gp120 (A, B, C, A/E)) contains equal amounts of 4 gp120 proteins.; Biological: Alhydrogel adjuvant; PDPHV protein vaccines adjuvant; Biological: PDPHV Plasmid DNA Vaccines (env (A, B, C, A/E)/gag (C)); The polyvalent DNA Vaccines contains equal amounts of 5 individual DNA plasmid components utilizing the same vector pSW3891. Four plasmids each containing a codon optimized gp120 gene sequence from HIV-1 subtype A, B, C and CRF01_AE consensus, and a fifth plasmid containing a codon optimized gag gene from subtype C.
Placebo Comparator: Group 2 (Control); Participants will receive Placebo to be administered as a 0.8 mL (IM) injection in the deltoid of the DOMINANT arm at Months 0 and 1; And Placebo to be administered as a 1 mL (IM) injection in the deltoid of the NON-DOMINANT arm at months 3 and 6.	Biological: Placebo for DNA Vaccines, Protein Vaccines and Adjuvants; Sodium Chloride for Injection, USP 0.9%.
Experimental: Group 3 (Treatment): DNA Vaccines prime, Protein Vaccines/GLA-SE; Participants will receive 2000 mcg Plasmid DNA Vaccine to be administered as a 0.8 mL (IM) injection in the deltoid of the DOMINANT arm at months 0, and 1; and 400 mcg Recombinant Protein Vaccines admixed with 5 mcg GLA-SE, to be administered as a 1 mL (IM) injection in the deltoid of the NON-DOMINANT arm at months 3 and 6.	Biological: PDPHV Recombinant Protein Vaccines (gp120 (A, B, C, A/E)); The Recombinant Protein Vaccines (gp120 (A, B, C, A/E)) contains equal amounts of 4 gp120 proteins.; Biological: PDPHV Plasmid DNA Vaccines (env (A, B, C, A/E)/gag (C)); The polyvalent DNA Vaccines contains equal amounts of 5 individual DNA plasmid components utilizing the same vector pSW3891. Four plasmids each containing a codon optimized gp120 gene sequence from HIV-1 subtype A, B, C and CRF01_AE consensus, and a fifth plasmid containing a codon optimized gag gene from subtype C.; Biological: GLA-SE adjuvant; PDPHV protein vaccines adjuvant
Placebo Comparator: Group 3 (Control); Participants will receive Placebo to be administered as a 0.8 mL (IM) injection in the deltoid of the DOMINANT arm at Months 0, and 1; and Placebo to be administered as a 1 mL (IM) injection in the deltoid of the NON-DOMINANT arm at months 3 and 6.	Biological: Placebo for DNA Vaccines, Protein Vaccines and Adjuvants; Sodium Chloride for Injection, USP 0.9%.
Experimental: Group 4 (Treatment): DNA Vaccines prime, Protein Vaccines/Alhydrogel + DNA Vaccines boost; Participants will receive 2000 mcg Plasmid DNA Vaccines to be administered as a 0.8 mL (IM) injection in the deltoid of the DOMINANT arm at months 0, 1, 3, and 6; and 400 mcg Recombinant Protein Vaccines admixed with 800 mcg Alhydrogel, to be administered as a 1 mL (IM) injection in the deltoid of the NON-DOMINANT arm at months 3 and 6.	Biological: PDPHV Recombinant Protein Vaccines (gp120 (A, B, C, A/E)); The Recombinant Protein Vaccines (gp120 (A, B, C, A/E)) contains equal amounts of 4 gp120 proteins.; Biological: Alhydrogel adjuvant; PDPHV protein vaccines adjuvant; Biological: PDPHV Plasmid DNA Vaccines (env (A, B, C, A/E)/gag (C)); The polyvalent DNA Vaccines contains equal amounts of 5 individual DNA plasmid components utilizing the same vector pSW3891. Four plasmids each containing a codon optimized gp120 gene sequence from HIV-1 subtype A, B, C and CRF01_AE consensus, and a fifth plasmid containing a codon optimized gag gene from subtype C.
Placebo Comparator: Group 4 (Control); Participants will receive Placebo to be administered as a 0.8 mL (IM) injection in the deltoid of the DOMINANT arm at Months 0, 1, 3, and 6; and Placebo for to be administered as a 1 mL (IM) injection in the deltoid of the NON-DOMINANT arm at months 3 and 6.	Biological: Placebo for DNA Vaccines, Protein Vaccines and Adjuvants; Sodium Chloride for Injection, USP 0.9%.
Experimental: Group 5 (Treatment): DNA Vaccines prime, Protein Vaccines/GLA-SE + DNA vaccines boost; Participants will receive 2000 mcg Plasmids DNA Vaccines to be administered as a 0.8 mL (IM) injection in the deltoid of the DOMINANT arm at months 0, 1, 3, and 6; and 400 mcg Recombinant Protein Vaccines admixed with 5 mcg GLA-SE, to be administered as a 1 mL (IM) injection in the deltoid of the NON-DOMINANT arm at months 3 and 6.	Biological: PDPHV Recombinant Protein Vaccines (gp120 (A, B, C, A/E)); The Recombinant Protein Vaccines (gp120 (A, B, C, A/E)) contains equal amounts of 4 gp120 proteins.; Biological: PDPHV Plasmid DNA Vaccines (env (A, B, C, A/E)/gag (C)); The polyvalent DNA Vaccines contains equal amounts of 5 individual DNA plasmid components utilizing the same vector pSW3891. Four plasmids each containing a codon optimized gp120 gene sequence from HIV-1 subtype A, B, C and CRF01_AE consensus, and a fifth plasmid containing a codon optimized gag gene from subtype C.; Biological: GLA-SE adjuvant; PDPHV protein vaccines adjuvant
Placebo Comparator: Group 5 (Control); Participants will receive Placebo to be administered as a 0.8 mL (IM) injection in the deltoid of the DOMINANT arm at Months 0, 1, 3, and 6; and Placebo to be administered as a 0.9 mL (IM) injection into the deltoid of the NON-DOMINANT arm at months 3 and 6.	Biological: Placebo for DNA Vaccines, Protein Vaccines and Adjuvants; Sodium Chloride for Injection, USP 0.9%.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of local injection site (including DTH) reactogenicity signs and symptoms	Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017	Measured through participants' last study visit, at Month 15 or 18, depending on which part of the study participants are enrolled in
Frequency of systemic reactogenicity signs and symptoms	Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017	Measured through participants' last study visit, at Month 15 or 18, depending on which part of the study participants are enrolled in
Frequency of adverse events (AEs)	AEs categorized by Medical Dictionary for Regulatory Activities (MedDRA) system organ class, MedDRA preferred term, severity, and assessed relationship to study products	Measured through participants' last study visit, at Month 15 or 18, depending on which part of the study participants are enrolled in
Severity of local injection site (including DTH) reactogenicity signs and symptoms	Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017	Measured through participants' last study visit, at Month 15 or 18, depending on which part of the study participants are enrolled in
Severity of systemic reactogenicity signs and symptoms	Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017	Measured through participants' last study visit, at Month 15 or 18, depending on which part of the study participants are enrolled in
Severity of adverse events (AEs)	AEs categorized by MedDRA system organ class, MedDRA preferred term, severity, and assessed relationship to study products	Measured through participants' last study visit, at Month 15 or 18, depending on which part of the study participants are enrolled in
Number of participants with early discontinuation of vaccinations	Tabulated by reason and treatment arm	Measured through participants' last study visit, at Month 15 or 18, depending on which part of the study participants are enrolled in
Magnitude of serum HIV-1 Env-specific IgG responses	Assessed by ELISA or Binding Antibody Multiplex Assay	Measured at 2 weeks after the last vaccination at month 6.5
Breadth of gp70-V1V2 IgG and gp120 IgA	Assessed by ELISA or Binding Antibody Multiplex Assay.	Measured at 2 weeks after the last vaccination at month 6.5
ADCC activities	Assessed by GranToxiLux assay	Measured at 2 weeks after the last vaccination at month 6.5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum neutralizing antibody responses against Tier 1A, Tier 1B, and selected Tier 2 viruses	Assessed by TZM-bl assay	Measured at 2 weeks after the last vaccination at month 6.5
Frequency of HIV-1 specific CD4+ and CD8+ T-cell responses	Assessed by intracellular cytokine staining (ICS)	Measured at 2 weeks after the last vaccination at month 6.5

Collaborators and Investigators

• Sponsor: Worcester HIV Vaccine
• Collaborators: Brigham and Women's Hospital; Desmond Tutu Health Foundation
• Investigators: Principal Investigator: Conasagrie Nair, PhD, MD, Desmond Tutu Health Foundation; Principal Investigator: Stephen Walsh, PhD, MD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: June 9, 2026
• First Submitted That Met QC Criteria: June 25, 2026
• First Posted (Actual): June 30, 2026

Study Record Updates

• Last Update Posted (Actual): June 30, 2026
• Last Update Submitted That Met QC Criteria: June 25, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: HIV-1; vaccine; antibody; human study
• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Genome Components; Genome; Genetic Structures; Genetic Phenomena; Biological Products; Complex Mixtures; Vaccines; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Antigens; Genes; HIV Antigens; Antigens, Viral; Viral Proteins; env Gene Products, Human Immunodeficiency Virus; Gene Products, env; Retroviridae Proteins; Human Immunodeficiency Virus Proteins; Viral Envelope Proteins; Viral Structural Proteins; Genes, Viral; Genes, Microbial; Genome, Microbial; Genome, Viral; Vaccines, DNA; glucopyranosyl lipid-A; Genes, env; HIV Envelope Protein gp120
• Other Study ID Numbers: WHV238

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data obtained through this study may be provided to qualified researchers with academic interest. Data will be deidentified, and access requires approval of a research proposal, execution of a Data Sharing Agreement, and IRB approval. Requests can be submitted starting 9 months after publication and will be available for up to 24 months.

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