Presentation of HIV-1 envelope glycoprotein trimers on diverse nanoparticle platforms

Philip J.M. Brouwer, Rogier W. Sanders

We will discuss recent advances in the development of nanoparticle vaccines presenting HIV-1 envelope trimer vaccines and the immunological mechanisms by which they act. The multivalent presentation of Env trimers on nanoparticles is a promising strategy to increase Env immunogenicity. Recent studies have shed light on how Env nanoparticles increase lymph node trafficking and germinal center formation by using the lectin-mediated complement pathway and enhancing the interaction with naïve B cells. Meanwhile, research on different nanoparticle platforms has resulted in improved designs, such as liposomes with improved stability, and the emergence of novel platforms such as protein nanoparticles that self-assemble in vitro. Immmunogenicity studies with these nanoparticles delineate the advantages and expose the limitations of the different nanoparticle platforms. It is becoming increasingly clear that HIV-1 vaccine research might benefit greatly from using nanoparticles presenting Env trimers, particularly during the priming stage of immunization. Among the different nanoparticles that are being pursued, in vitro-assembling nanoparticles allow for greater control of Env quality making them a promising nanoparticle platform.