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.
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.
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.
The Recombinant Protein Vaccines (gp120 (A, B, C, A/E)) contains equal amounts of 4 gp120 proteins.
PDPHV protein vaccines adjuvant
Brigham and Women's Hospital
Boston, Massachusetts, United States
Emavundleni Clinical Research Site, Desmond Tutu Health Foundation
Cape Town, South Africa
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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Measured through participants' last study visit, at Month 15 or 18, depending on which part of the study participants are enrolled in
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Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
126
PDPHV protein vaccines adjuvant
Sodium Chloride for Injection, USP 0.9%.
Severity of adverse events (AEs)
AEs categorized by MedDRA system organ class, MedDRA preferred term, severity, and assessed relationship to study products
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: Measured at 2 weeks after the last vaccination at month 6.5
ADCC activities
Assessed by GranToxiLux assay
Time frame: Measured at 2 weeks after the last vaccination at month 6.5
Serum neutralizing antibody responses against Tier 1A, Tier 1B, and selected Tier 2 viruses
Assessed by TZM-bl assay
Time frame: 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)
Time frame: Measured at 2 weeks after the last vaccination at month 6.5