HIV PreventionPhase 2NCT07675629
Evaluating the Safety and Immunogenicity of Polyvalent DNA and Recombinant gp120 Protein HIV Vaccine (PDPHV) in Healthy, HIV-uninfected Adults
A Phase 2 study testing PDPHV Plasmid DNA Vaccines (env (A, B, C, A/E)/gag (C)), PDPHV Recombinant Protein Vaccines (gp120 (A, B, C, A/E)) and Alhydrogel adjuvant in people with HIV Prevention, run by Worcester HIV Vaccine at 2 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV Prevention
- What is being tested?
- PDPHV Plasmid DNA Vaccines (env (A, B, C, A/E)/gag (C)), PDPHV Recombinant Protein Vaccines (gp120 (A, B, C, A/E)) and Alhydrogel adjuvant
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 126 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 1 Sep 2026to Aug 2029
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age of 18 to 55 years
- Access to a trial site and willingness to be followed for the planned duration of the study.
- Ability and willingness to provide informed consent
- Demonstrates an understanding of the study
- 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
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- 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.
- Hemoglobin ≥ 11.0 g/dL for volunteers who were born female, ≥ 12.0 g/dL for volunteers who were born male
- White blood cell count = 3,000 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 450,000/mm3
- Chemistry panel: ALT< 1.25 times the institutional upper limit of normal; creatinine < 1.1 times institutional upper limit of normal.
- Negative HIV-1 and -2 blood test
- Negative Hepatitis B surface antigen (HBsAg)
- Negative anti-Hepatitis C virus antibodies (anti-HCV)
- 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)
- 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.
- 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.
- 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.
Who cannot join
- Blood products received within 120 days before first vaccination.
- Investigational research agents received within 30 days before first vaccination.
- Body mass index (BMI) ≥ 40.
- Intent to participate in another study of an investigational research agent or any other study that requires HIV antibody testing.
- Pregnant or breastfeeding.
- Active duty and reserve US military personnel.
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- HIV vaccine(s) received in a prior HIV vaccine trial.
- 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.
- Live attenuated vaccines, other than the influenza vaccine, received within 30 days before first vaccination or scheduled within 14 days after injection.
- Any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination.
- Allergy treatment with antigen injections within 30 days before the first vaccination or those that are scheduled within 14 days after the first vaccination
- Immunosuppressive medications received within 168 days before the first vaccination.
- 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.
- Immunoglobulin received within 60 days before the first vaccination.
- 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.
- Immunodeficiency.
- 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.
- Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or reactogenicity, or a volunteer's ability to give informed consent.
- Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years.
- Current anti-tuberculosis (TB) prophylaxis or therapy.
- Asthma other than mild, well-controlled asthma
- Diabetes mellitus type 1 or type 2, including cases controlled with diet alone. (Not excluded: history of isolated gestational diabetes.)
- 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.
- 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.
- Bleeding disorder diagnosed by a doctor.
- Malignancy.
- Seizure disorder: History of seizure(s) within past three years.
- Asplenia: any condition resulting in the absence of a functional spleen.
- History of hereditary angioedema, acquired angioedema, or idiopathic angioedema.
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Stephen Walsh
South Africa1 site
Emavundleni Clinical Research Site, Desmond Tutu Health Foundation
Cape Town
Conasagrie Nair
About this study
Official title: 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.
Read the 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.
- Conditions
- HIV Prevention
- Being tested
- PDPHV Plasmid DNA Vaccines (env (A, B, C, A/E)/gag (C)), PDPHV Recombinant Protein Vaccines (gp120 (A, B, C, A/E)), Alhydrogel adjuvant, GLA-SE adjuvant, Placebo for DNA Vaccines, Protein Vaccines and Adjuvants
- Keywords
- HIV-1, vaccine, antibody, human study
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PDPHV Plasmid DNA Vaccines (env (A, B, C, A/E)/gag (C))Biological
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.
PDPHV Recombinant Protein Vaccines (gp120 (A, B, C, A/E))Biological
The Recombinant Protein Vaccines (gp120 (A, B, C, A/E)) contains equal amounts of 4 gp120 proteins.
Alhydrogel adjuvantBiological
PDPHV protein vaccines adjuvant
GLA-SE adjuvantBiological
PDPHV protein vaccines adjuvant
Placebo for DNA Vaccines, Protein Vaccines and AdjuvantsBiological
Sodium Chloride for Injection, USP 0.9%.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 (Treatment): Protein Vaccines/Alhydrogel | Experimental | 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. Receives: Biological: PDPHV Recombinant Protein Vaccines (gp120 (A, B, C, A/E)); Biological: Alhydrogel adjuvant |
| Group 1 (Control) | Placebo comparator | 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. Receives: Biological: Placebo for DNA Vaccines, Protein Vaccines and Adjuvants |
| Group 2 (Treatment): DNA Vaccines prime, Protein Vaccines/Alhydrogel boost | Experimental | 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. Receives: Biological: PDPHV Plasmid DNA Vaccines (env (A, B, C, A/E)/gag (C)); Biological: PDPHV Recombinant Protein Vaccines (gp120 (A, B, C, A/E)); Biological: Alhydrogel adjuvant |
| Group 2 (Control) | Placebo comparator | 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. Receives: Biological: Placebo for DNA Vaccines, Protein Vaccines and Adjuvants |
| Group 3 (Treatment): DNA Vaccines prime, Protein Vaccines/GLA-SE | Experimental | 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. Receives: Biological: PDPHV Plasmid DNA Vaccines (env (A, B, C, A/E)/gag (C)); Biological: PDPHV Recombinant Protein Vaccines (gp120 (A, B, C, A/E)); Biological: GLA-SE adjuvant |
| Group 3 (Control) | Placebo comparator | 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. Receives: Biological: Placebo for DNA Vaccines, Protein Vaccines and Adjuvants |
| Group 4 (Treatment): DNA Vaccines prime, Protein Vaccines/Alhydrogel + DNA Vaccines boost | Experimental | 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. Receives: Biological: PDPHV Plasmid DNA Vaccines (env (A, B, C, A/E)/gag (C)); Biological: PDPHV Recombinant Protein Vaccines (gp120 (A, B, C, A/E)); Biological: Alhydrogel adjuvant |
| Group 4 (Control) | Placebo comparator | 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. Receives: Biological: Placebo for DNA Vaccines, Protein Vaccines and Adjuvants |
| Group 5 (Treatment): DNA Vaccines prime, Protein Vaccines/GLA-SE + DNA vaccines boost | Experimental | 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. Receives: Biological: PDPHV Plasmid DNA Vaccines (env (A, B, C, A/E)/gag (C)); Biological: PDPHV Recombinant Protein Vaccines (gp120 (A, B, C, A/E)); Biological: GLA-SE adjuvant |
| Group 5 (Control) | Placebo comparator | 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. Receives: Biological: Placebo for DNA Vaccines, Protein Vaccines and Adjuvants |
What is being measured
The primary outcome is the main question the study is designed to answer.
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: 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: 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: 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: 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: 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: 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: 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: 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: Measured at 2 weeks after the last vaccination at month 6.5
ADCC activities
Assessed by GranToxiLux assay
Measured: Measured at 2 weeks after the last vaccination at month 6.5
Secondary outcomes (2)
Serum neutralizing antibody responses against Tier 1A, Tier 1B, and selected Tier 2 viruses
Assessed by TZM-bl assay
Measured: 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: Measured at 2 weeks after the last vaccination at month 6.5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2026
- Study start1 Sep 2026 (estimated)
- Primary completion31 Aug 2028 (estimated)
- Study completionAug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV PreventionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 126 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Worcester HIV Vaccine
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Desmond Tutu Health Foundation, Brigham and Women's Hospital
- Responsible party
- Sponsor
- Investigators
- Conasagrie Nair, PhD, MD, Principal investigator, Desmond Tutu Health FoundationStephen Walsh, PhD, MD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07675629
- Sponsor's protocol ID
- WHV238
- Status last verified
- Jun 2026
- First submitted
- 9 Jun 2026
- Last updated
- 30 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.