EMD-24853

Single-particle
5.2 Å
EMD-24853 Deposition: 13/09/2021
Map released: 06/04/2022
Last modified: 06/04/2022
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-24853

Modified BG505 SOSIP-based immunogen RC1 in complex with elicited mAb Ab283MUR Fab and 8ANC195 Fab

EMD-24853

Single-particle
5.2 Å
EMD-24853 Deposition: 13/09/2021
Map released: 06/04/2022
Last modified: 06/04/2022
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Mus musculus, Human immunodeficiency virus 1, Homo sapiens
Sample: Elicited Ab283MUR Fab in complex with RC1 SOSIP and bNAb 8ANC195 Fab

Deposition Authors: Abernathy ME , Bjorkman PJ
Sequential immunization of macaques elicits heterologous neutralizing antibodies targeting the V3-glycan patch of HIV-1 Env.
PUBMED: 34818054
DOI: doi:10.1126/scitranslmed.abk1533
ISSN: 1946-6242
Abstract:
Broadly neutralizing antibodies (bNAbs) against HIV-1 develop after prolonged virus and antibody coevolution. Previous studies showed that sequential immunization with a V3-glycan patch germline-targeting HIV-1 envelope trimer (Env) followed by variant Envs can reproduce this process in mice carrying V3-glycan bNAb precursor B cells. However, eliciting bNAbs in animals with polyclonal antibody repertoires is more difficult. We used a V3-glycan immunogen multimerized on virus-like particles (VLPs), followed by boosting with increasingly native-like Env-VLPs, to elicit heterologous neutralizing antibodies in nonhuman primates (NHPs). Structures of antibody/Env complexes after prime and boost vaccinations demonstrated target epitope recognition with apparent maturation to accommodate glycans. However, we also observed increasing off-target antibodies with boosting. Eight vaccinated NHPs were subsequently challenged with simian-human immunodeficiency virus (SHIV), and seven of eight animals became infected. The single NHP that remained uninfected after viral challenge exhibited one of the lowest neutralization titers against the challenge virus. These results demonstrate that more potent heterologous neutralization resulting from sequential immunization is necessary for protection in this animal model. Thus, improved prime-boost regimens to increase bNAb potency and stimulate other immune protection mechanisms are essential for developing anti–HIV-1 vaccines.