Structural topology defines protective CD8 ⁺ T cell epitopes in the HIV proteome

Structure-based immunogen design Vaccine design for highly mutable pathogens is hindered by a paucity of conserved immunogenic epitopes. Gaiha et al. employed a structure-based technique using network theory to assign scores to protein structure in order to infer mutational constraints (see the Perspective by McMichael and Carrington). The authors validated the method on proteins with published functional outcomes and then assessed mutational constraints within the HIV proteome. Highly networked residues strongly associated with immune control of HIV infection and may lead to protective immunogens for pathogens for which there is currently no efficient vaccine. Science , this issue p. 480 ; see also p. 438