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TitleStabilized HIV-1 envelope immunization induces neutralizing antibodies to the CD4bs and protects macaques against mucosal infection.
Journal, issue, pagesSci Transl Med, Vol. 14, Issue 661, Page eabo5598, Year 2022
Publish dateSep 7, 2022
AuthorsKevin O Saunders / Robert J Edwards / Kedamawit Tilahun / Kartik Manne / Xiaozhi Lu / Derek W Cain / Kevin Wiehe / Wilton B Williams / Katayoun Mansouri / Giovanna E Hernandez / Laura Sutherland / Richard Scearce / Robert Parks / Maggie Barr / Todd DeMarco / Chloe M Eater / Amanda Eaton / Georgeanna Morton / Benjamin Mildenberg / Yunfei Wang / R Wes Rountree / Mark A Tomai / Christopher B Fox / M Anthony Moody / S Munir Alam / Sampa Santra / Mark G Lewis / Thomas N Denny / George M Shaw / David C Montefiori / Priyamvada Acharya / Barton F Haynes /
PubMed AbstractA successful HIV-1 vaccine will require induction of a polyclonal neutralizing antibody (nAb) response, yet vaccine-mediated induction of such a response in primates remains a challenge. We found ...A successful HIV-1 vaccine will require induction of a polyclonal neutralizing antibody (nAb) response, yet vaccine-mediated induction of such a response in primates remains a challenge. We found that a stabilized HIV-1 CH505 envelope (Env) trimer formulated with a Toll-like receptor 7/8 agonist induced potent HIV-1 polyclonal nAbs that correlated with protection from homologous simian-human immunodeficiency virus (SHIV) infection. The serum dilution that neutralized 50% of virus replication (ID titer) required to protect 90% of macaques was 1:364 against the challenge virus grown in primary rhesus CD4 T cells. Structural analyses of vaccine-induced nAbs demonstrated targeting of the Env CD4 binding site or the N156 glycan and the third variable loop base. Autologous nAb specificities similar to those elicited in macaques by vaccination were isolated from the human living with HIV from which the CH505 Env immunogen was derived. CH505 viral isolates were isolated that mutated the V1 to escape both the infection-induced and vaccine-induced antibodies. These results define the specificities of a vaccine-induced nAb response and the protective titers of HIV-1 vaccine-induced nAbs required to protect nonhuman primates from low-dose mucosal challenge by SHIVs bearing a primary transmitted/founder Env.
External linksSci Transl Med / PubMed:36070369 / PubMed Central
MethodsEM (single particle)
Resolution10.4 - 18.4 Å
Structure data

EMDB-24619:
Negative stain electron microscopy single particle reconstruction of monoclonal antibody DH1024 Fab in complex with HIV-1 Env CH505 SOSIP trimer
Method: EM (single particle) / Resolution: 15.0 Å

EMDB-24620:
Negative stain electron microscopy single particle reconstruction of monoclonal antibody DH1025.1 Fab in complex with HIV-1 Env CH505 SOSIP trimer
Method: EM (single particle) / Resolution: 10.4 Å

EMDB-24621:
Negative stain electron microscopy single particle reconstruction of monoclonal antibody DH1027 Fab in complex with HIV-1 Env CH505 SOSIP trimer.
Method: EM (single particle) / Resolution: 18.4 Å

EMDB-24622:
Negative stain electron microscopy single particle reconstruction of monoclonal antibody DH1028 Fab in complex with HIV-1 Env CH505 SOSIP trimer.
Method: EM (single particle) / Resolution: 12.9 Å

EMDB-24623:
Negative stain electron microscopy single particle reconstruction of monoclonal antibody DH950 Fab in complex with HIV-1 Env CH505 SOSIP trimer.
Method: EM (single particle) / Resolution: 15.4 Å

Source
  • Human immunodeficiency virus 2
  • Macaca mulatta (Rhesus monkey)
  • Human immunodeficiency virus 1
  • Homo sapiens (human)

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