Glycosylation of the HIV-1 Env V1V2 loop to form a native-like structure may not be essential with a nanoparticle vaccine

Karch, Christopher P; Matyas, Gary R; Burkhard, Peter; Beck, Zoltan

A major effort has been undertaken to understand the role of glycans in respect to broadly neutralizing antibodies (bnAbs) to the Env protein of HIV-1 [26] . Some of these antibodies directly interact with glycans. A well-known bnAb that exclusively recognizes the glycosylation pattern is 2G12 [23] . Most of the bnAbs interacting with both the glycan and the amino acid sequence of gp120 have structural features, such as long CDRH3 loops, to penetrate the glycan shield [27] . Binding to the virus and neutralization by many of these bnAbs primarily depend on the quaternary structure of the protein, which can, however, be affected by the presence of the glycans. Between 10 and 30% of people infected with HIV-1 develop bnAbs with cross-clade neutralizing activity within 3 years of infection but while controlling the infection, it does not result in sterilizing immunity [28] . Considering that only a small fraction of antibodies to HIV-1 elicit broadly neutralizing function, the low concentration of these bnAbs in vivo, and their late occurrence during disease progression; a potentially different approach to generate bnAbs for an effective prophylactic vaccine may be necessary [26] . It raises the question: is it possible to induce high titer bnAbs with high binding affinity to the virus with an Env immunogen that is not glycosylated, but maintains the conformation of the protein?