We use our accumulated knowledge of the structure and function of the HIV-1 envelope (Env) glycoprotein trimer to design and evaluate recombinant forms of these proteins as immunogens for vaccine development. In the initial stages of the virus replication cycle, the envelope glycoproteins attach HIV-1 to its susceptible target cells, which are predominantly CD4-positive T-cells, macrophages and dendritic cells. The Env trimer then undergoes a series of receptor-mediated conformational changes that enable the virus and cell membranes to fuse, and the virus to infect the cell. The Env glycoproteins are also critical targets for host immunity, particularly virus neutralizing antibodies (NAbs). These antibodies bind to functional Env glycoproteins on the virus surface and block their activity. Inducing broadly active NAbs by immunization with Env glycoproteins would, therefore, be a valuable component of a vaccine to prevent HIV-1 infection. To this end, we have designed and are developing stable, recombinant trimers that faithfully mimic the native, functional trimers that are present on the virus surface. These trimers, called SOSIP glycoproteins, induce narrow-specificity NAbs in test animals, and we are working to broaden these responses. All of this work is carried out as part of a multi-disciplinary team with colleagues in other institutions, including structural biologists and immunologists.