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TitleImmunization with germ line-targeting SOSIP trimers elicits broadly neutralizing antibody precursors in infant macaques.
Journal, issue, pagesSci Immunol, Vol. 9, Issue 98, Page eadm7097, Year 2024
Publish dateAug 30, 2024
AuthorsAshley N Nelson / Xiaoying Shen / Sravani Vekatayogi / Shiyu Zhang / Gabriel Ozorowski / Maria Dennis / Leigh M Sewall / Emma Milligan / Dominique Davis / Kaitlyn A Cross / Yue Chen / Jelle van Schooten / Joshua Eudailey / John Isaac / Saad Memon / Carolyn Weinbaum / Hongmei Gao / Sherry Stanfield-Oakley / Alliyah Byrd / Suni Chutkan / Stella Berendam / Kenneth Cronin / Anila Yasmeen / S Alam / Celia C LaBranche / Kenneth Rogers / Lisa Shirreff / Albert Cupo / Ronald Derking / Francois Villinger / Per Johan Klasse / Guido Ferrari / Wilton B Williams / Michael G Hudgens / Andrew B Ward / David C Montefiori / Koen K A Van Rompay / Kevin Wiehe / John P Moore / Rogier W Sanders / Kristina De Paris / Sallie R Permar /
PubMed AbstractAdolescents are a growing population of people living with HIV. The period between weaning and sexual debut presents a low-risk window for HIV acquisition, making early childhood an ideal time for ...Adolescents are a growing population of people living with HIV. The period between weaning and sexual debut presents a low-risk window for HIV acquisition, making early childhood an ideal time for implementing an immunization regimen. Because the elicitation of broadly neutralizing antibodies (bnAbs) is critical for an effective HIV vaccine, our goal was to assess the ability of a bnAb B cell lineage-designed HIV envelope SOSIP (protein stabilized by a disulfide bond between gp120-gp41-named "SOS"-and an isoleucine-to-proline point mutation-named "IP"-at residue 559) to induce precursor CD4 binding site (CD4bs)-targeting bnAbs in early life. Infant rhesus macaques received either a BG505 SOSIP, based on the infant BG505 transmitted/founder virus, or the CD4bs germ line-targeting BG505 SOSIP GT1.1 ( = 5 per group). Although both strategies induced durable, high-magnitude plasma autologous virus neutralization responses, only GT1.1-immunized infants ( = 3 of 5) exhibited VRC01-like CD4bs bnAb precursor development. Thus, a multidose immunization regimen with bnAb lineage-designed SOSIPs shows promise for inducing early B cell responses with the potential to mature into protective HIV bnAbs before sexual debut.
External linksSci Immunol / PubMed:39213340
MethodsEM (single particle)
Resolution25.0 - 30.0 Å
Structure data

EMDB-41869: BG505.664 SOSIP in complex with polyclonal antibodies from NHP 8131 (gp120 glycan hole, gp41 glycan hole/fusion peptide and trimer base epitopes)
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-41870: BG505.664 Env SOSIP in complex with polyclonal antibodies from NHP 8131 (gp120-gp120 interface epitope)
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-41871: BG505.664 Env SOSIP in complex with polyclonal antibodies from NHP 8147 (C3/V5, V1/V2/V3 apex, gp41 glycan hole/fusion peptide and trimer base epitopes)
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-41872: BG505.664 Env SOSIP in complex with polyclonal antibodies from NHP 8147 (gp120 glycan hole epitope)
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-41972: GT1.1 SOSIP in complex with wk39 polyclonal antibodies from NHP A12N030 (CD4bs, C3V5 and base epitopes)
Method: EM (single particle) / Resolution: 30.0 Å

EMDB-41973: GT1.1 SOSIP in complex with wk39 polyclonal antibodies from NHP A12N030 (gp41GH/FP and base epitopes)
Method: EM (single particle) / Resolution: 30.0 Å

EMDB-41974: GT1.1 SOSIP in complex with wk39 polyclonal antibodies from NHP DC8G (gp41GH/FP and gp120GH epitopes)
Method: EM (single particle) / Resolution: 30.0 Å

EMDB-41975: GT1.1 SOSIP in complex with wk39 polyclonal antibodies from NHP DC8G (gp120GH and base epitopes)
Method: EM (single particle) / Resolution: 30.0 Å

EMDB-41976: GT1.1 SOSIP in complex with wk39 polyclonal antibodies from NHP DC8G (V1V2V3 and gp120GH epitopes)
Method: EM (single particle) / Resolution: 30.0 Å

EMDB-41977: GT1.1 SOSIP-CC2 in complex with wk80 polyclonal antibodies from NHP 8229 (V1V2V3, C3V5, CD4bs, gp41GH/FP and base epitopes)
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-41978: GT1.1 SOSIP-CC2 in complex with wk80 polyclonal antibodies from NHP 8239 (gp120GH, gp41GH/FP, CD4bs, and base epitopes)
Method: EM (single particle) / Resolution: 25.0 Å

Source
  • Human immunodeficiency virus 1
  • Macaca (macaques)
  • Macaca mulatta (Rhesus monkey)

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