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

Participants will be enrolled in Group 1 to group 5. Within each group, participants willbe randomly assigned to either Treatment or Placebo Control.Group 1 (Sentinel group) will be enrolled first to test the safety of the proteinvaccines mixed with the Alhydrogel adjuvant. Participants in Group 1 (Treatment) willreceive polyvalent gp120 (A, B, C, A/E) protein vaccines mixed with Alhydrogel in thenon‐dominant arm at months 0, and 3. Participants in Group 1 (Control) will receiveplacebo at months 0, and 3.The Safety Monitoring Board (SMB) will evaluate the safety profile of volunteers in Group1 in two weeks after the 2nd dose. The Alhydrogel adjuvanted Protein Vaccines boosts ingroup 2 and group 4 can only proceed after SMB reviews the safety data from Group 1 andapproves to the use of Alhydrogel in these studies.Participants in Group 2 (Treatment) will receive env (A, B, C, A/E)/gag (C) DNA Vaccinesin the dominant arm at months 0, and 1, followed by gp120 (A, B, C, A/E) Protein Vaccinesmixed with Alhydrogel boosts in the non‐dominant arm at Months 3, and 6. Participants inGroup 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 Vaccinesin the dominant arm at months 0, and 1, followed by gp120 (A, B, C, A/E) Protein Vaccinesmixed with GLA‐SE boosts in the non‐dominant arm at Months 3, and 6. Participants inGroup 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 Vaccinesin the dominant arm at months 0, and 1, followed by gp120 (A, B, C, A/E) Protein Vaccinesmixed with Alhydrogel boosts in the non‐dominant arm AND env (A, B, C, A/E)/gag (C) DNAVaccines in the dominant arm at Months 3, and 6. Participants in Group 4 (Control) willreceive placebo at Months 0, 1, 3, and 6.Participants in Group 5 (Treatment) will receive env (A, B, C, A/E)/gag (C) DNA Vaccinesin the dominant arm at months 0, and 1, followed by gp120 (A, B, C, A/E) Protein Vaccinesmixed with GLA‐SE boosts in the non‐dominant arm AND env (A, B, C, A/E)/gag (C) DNAVaccines in the dominant arm at Months 3, and 6. Participants in Group 5 (Control) willreceive 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, and15. 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 urinecollection, HIV testing, risk reduction counselling, and questionnaires.