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 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.