Inducing neutralizing antibodies against HIV by native-like envelope trimers Event

We have succeeded in generating stabilized mimics of the native envelope trimer by protein engineering. In contrast to previous envelope-based vaccine candidates, these trimers induce strong and consistent neutralizing antibody responses against the autologous, neutralization-resistant viruses. However, the induction of broadly-reactive neutralizing antibodies is more challenging. A critical step in this process is the activation of naïve B cells expressing germline antibody precursors that have the potential to evolve into broadly neutralizing antibodies.

We have reengineered stabilized native-like envelope trimers to engage germline precursors of broadly-reactive neutralizing antibodies. Immunization experiments in knock-in mouse models expressing broadly neutralizing antibody germline precursors show that these trimers activate germline precursor B cells in vivo. The antibody response in these knock-in mice can be further ‘shaped’ by the design and selection of next-step ‘shaping’ immunogens and ‘polishing’ immunogens. Finally, the design of native-like envelope trimers can also be applied to other viruses including Lassa virus and hepatitis C virus, resulting in neutralizing antibodies against these viruses