Stable immunogens comprising portions of the inner domain (ID) of the Human Immunodeficiency Virus (HIV-1) gp120 protein are provided. These ID immunogens selectively present the gp120 C1/C2 region in its CD4-bound state within a minimal structure. These ID immunogens can be used to vaccinate subjects against infection with HIV, the causative agent of Acquired Immunodeficiency Syndrome (AIDS). The immunogens can also be used as targets in screening to identify small molecule or peptide inhibitors that block HIV-1 viral entry and attachment steps, and as probes for identifying gp120 C1/C2 region-specific antibodies.
