Models of RNA virus evolution and their roles in vaccine design

Ojosnegros, Samuel; Beerenwinkel, Niko

Besides genetic heterogeneity, the development of an efficient vaccine against HIV remains elusive because of the difficulties of inducing an efficient immune response [98, 136] . Individuals who control infection display a strong cellular response [137] [138] [139] . Many experimental vaccines have failed in directing the effector response to a more cellular profile [140] . Furthermore, HIV infection induces a low titer of neutralizing antibodies [141, 142] . Gp120 and gp41 are the HIV proteins exposed at the surface of the virion. These proteins are responsible for the attachment of HIV to the cell surface and the virus has developed several strategies to avoid recognition and blocking by antibodies. The region of the protein that interacts with the CD4 cellular receptor is a hypervariable loop. A great number of antibody-escape mutants are mapped to this region of the HIV genome. The loop however, is highly glycosylated and it is only exposed at the surface of the protein in the precise moment of the interaction with the cellular receptor [143] . These two combined features complicate the fitting of potentially neutralizing antibodies [142] .