Interdomain Stabilization Impairs CD4 Binding and Improves Immunogenicity of the HIV-1 Envelope Trimer (Cell Host & Microbe)

Binding to CD4 compromises the native antigenic state of the HIV-1 envelope trimer. Zhang et al. rationally designed interdomain-locked trimers that elicited the production of tier-2 neutralizing antibodies against glycan-repaired virus and were resistant to CD4-induced disruption of immunogenicity. This strategy provides a widely applicable template for HIV-1 Env-based vaccines.