Immunogenicity of HIV-1 envelope glycoprotein oligomers

We summarize and discuss recent developments regarding the immunogenicity of human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) oligomers, focusing, for the most part, on trimeric, recombinant protein immunogens.

The three-dimensional cryo-electron tomography images of the HIV-1 Env trimeric spike, coupled with previous data demonstrating the impact on envelope glycoprotein (gp120)-transmembrane glycoprotein (gp41) cleavage of the architecture of the Env trimers, provide exciting information that may lead to new avenues for novel immunogen design. Through new processes to map region-specific anti-Env antibodies present in immune serum, it is now possible to define antibody specificities against conformationally sensitive surfaces of Env. A number of strategies designed to counteract the immunodominance of the HIV-1 Env variable regions were attempted, and a recent study demonstrates that immunization with Env trimers provides sterilizing protection against mucosal challenge with virus. Importantly, protection against the challenge virus was associated with in-vitro HIV-1 neutralization titers.

Several studies within the past 18 months provide exciting structural information and the development of tools that have the potential to improve Env trimer design and the analysis of trimer immunogenicity studies. The ability to predict protection against a challenge virus through an in-vitro neutralization screen may be very helpful for evaluation of immunogens to move forward into clinical trials.