Molecular insights into antibody-mediated protection against the prototypic simian immunodeficiency virus.
Fangzhu ZhaoZachary T BerndsenNuria Pedreño-LopezAlison BurnsJoel D AllenShawn BarmanWen-Hsin LeeSrirupa ChakrabortySandrasegaram GnanakaranLeigh M SewallGabriel OzorowskiOliver LimboSophie Ge SongPeter YongSean CallaghanJessica CoppolaKim L WeisgrauJeffrey D LifsonRebecca NedellecThomas B VoigtFernanda LaurinoJohan LouwBrandon C RosenMichael J RicciardiMax CrispinRonald C DesrosiersEva G RakaszDavid I WatkinsRaiees AndrabiAndrew B WardDennis R BurtonDevin SokPublished in: Nature communications (2022)
SIVmac239 infection of macaques is a favored model of human HIV infection. However, the SIVmac239 envelope (Env) trimer structure, glycan occupancy, and the targets and ability of neutralizing antibodies (nAbs) to protect against SIVmac239 remain unknown. Here, we report the isolation of SIVmac239 nAbs that recognize a glycan hole and the V1/V4 loop. A high-resolution structure of a SIVmac239 Env trimer-nAb complex shows many similarities to HIV and SIVcpz Envs, but with distinct V4 features and an extended V1 loop. Moreover, SIVmac239 Env has a higher glycan shield density than HIV Env that may contribute to poor or delayed nAb responses in SIVmac239-infected macaques. Passive transfer of a nAb protects macaques from repeated intravenous SIVmac239 challenge at serum titers comparable to those described for protection of humans against HIV infection. Our results provide structural insights for vaccine design and shed light on antibody-mediated protection in the SIV model.
Keyphrases
- antiretroviral therapy
- hiv infected
- high resolution
- hiv positive
- human immunodeficiency virus
- hepatitis c virus
- hiv aids
- advanced non small cell lung cancer
- endothelial cells
- transcription factor
- hiv testing
- mass spectrometry
- high dose
- low dose
- cell surface
- dengue virus
- epidermal growth factor receptor
- high speed
- electron transfer
- solar cells