Abstract
Original language | English |
---|---|
Article number | 101003 |
Journal | Cell Reports Medicine |
Volume | 4 |
Issue number | 4 |
DOIs | |
Publication status | Published - 18 Apr 2023 |
Keywords
- HIV-1 Env
- NGS
- bNAbs
- deletions
- germline-targeting
- insertions
- mouse model
- neutralizing antibodies
- vaccines
Access to Document
Other files and links
Cite this
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver
}
In: Cell Reports Medicine, Vol. 4, No. 4, 101003, 18.04.2023.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Germline-targeting HIV-1 Env vaccination induces VRC01-class antibodies with rare insertions
AU - Caniels, Tom G.
AU - Medina-Ramírez, Max
AU - Zhang, Jinsong
AU - Sarkar, Anita
AU - Kumar, Sonu
AU - LaBranche, Alex
AU - Derking, Ronald
AU - Allen, Joel D.
AU - Snitselaar, Jonne L.
AU - Capella-Pujol, Joan
AU - Sánchez, Iván del Moral
AU - Yasmeen, Anila
AU - Diaz, Marilyn
AU - Aldon, Yoann
AU - Bijl, Tom P. L.
AU - Venkatayogi, Sravani
AU - Martin Beem, Joshua S.
AU - Newman, Amanda
AU - Jiang, Chuancang
AU - Lee, Wen-Hsin
AU - Pater, Maarten
AU - Burger, Judith A.
AU - van Breemen, Mariëlle J.
AU - de Taeye, Steven W.
AU - Rantalainen, Kimmo
AU - LaBranche, Celia
AU - Saunders, Kevin O.
AU - Montefiori, David
AU - Ozorowski, Gabriel
AU - Ward, Andrew B.
AU - Crispin, Max
AU - Moore, John P.
AU - Klasse, Per Johan
AU - Haynes, Barton F.
AU - Wilson, Ian A.
AU - Wiehe, Kevin
AU - Verkoczy, Laurent
AU - Sanders, Rogier W.
N1 - Funding Information: We are grateful to the staff of Advanced Photon Source BL 23-IDD for assistance. GM/CA@APS has been funded by the National Cancer Institute ( ACB-12002 ) and the National Institute of General Medical Sciences ( AGM-12006 , P30GM138396 ). This research used resources of the Advanced Photon Sciences under contract no. DE-AC02-06CH11357 . This work is supported by the Netherlands Organisation for Scientific Research (N.W.O.) Vici grant (R.W.S.); Bill & Melinda Gates Foundation , Collaboration for AIDS Vaccine Discovery (C.A.V.D.) grants INV-002022 (R.W.S.) and OPP1115782 / INV-002916 (A.B.W.); Fondation Dormeur, Vaduz (R.W.S.); and grants from the NIAID , Division of AIDS , NIH UM1 grants for the Duke Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery (CHAVI-ID; UM1530AI100645 and Consortia for HIV/AIDS Vaccine Development [ CHAVD ]) UM1AI144371 to B.F.H. and R01 grant AI087202 (L.K.V.). P.J.K. and J.P.M. are supported by R01 AI036082 and A.B.W., I.A.W., R.W.S., P.J.K., and J.P.M. are supported by a HIVRAD P01 AI110657 grant. M.C. is funded by the International AIDS Vaccine Initiative (IAVI) through grant INV-008352 and the Bill & Melinda Gates Foundation OPP1153692 . Funding for the neutralization assays was provided by NIH / NIAID contract #HHSN272201800004C . Funding Information: We are grateful to the staff of Advanced Photon Source BL 23-IDD for assistance. GM/CA@APS has been funded by the National Cancer Institute (ACB-12002) and the National Institute of General Medical Sciences (AGM-12006, P30GM138396). This research used resources of the Advanced Photon Sciences under contract no. DE-AC02-06CH11357. This work is supported by the Netherlands Organisation for Scientific Research (N.W.O.) Vici grant (R.W.S.); Bill & Melinda Gates Foundation, Collaboration for AIDS Vaccine Discovery (C.A.V.D.) grants INV-002022 (R.W.S.) and OPP1115782/INV-002916 (A.B.W.); Fondation Dormeur, Vaduz (R.W.S.); and grants from the NIAID, Division of AIDS, NIH UM1 grants for the Duke Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery (CHAVI-ID; UM1530AI100645 and Consortia for HIV/AIDS Vaccine Development [CHAVD]) UM1AI144371 to B.F.H. and R01 grant AI087202 (L.K.V.). P.J.K. and J.P.M. are supported by R01 AI036082 and A.B.W. I.A.W. R.W.S. P.J.K. and J.P.M. are supported by a HIVRAD P01 AI110657 grant. M.C. is funded by the International AIDS Vaccine Initiative (IAVI) through grant INV-008352 and the Bill & Melinda Gates Foundation OPP1153692. Funding for the neutralization assays was provided by NIH/NIAID contract #HHSN272201800004C. Conceptualization: M.M.-R. R.D. B.F.H. L.W. L.K.V. and R.W.S.; investigation: T.G.C. M.M.-R. J.Z. A.S. A.S.K. A.L. R.D. J.A. J.L.S. J.C.P. I.d.M.S. A.Y. M.D. Y.A. T.P.L.B. S.V. J.M.B. A.N. C.J. W.-H.L. M.P. J.A.B. M.J.v.B. and P.J.K.; methodology: T.G.C. M.M.-R. J.Z. A.S. S.K. M.P. M.C. P.J.K. I.A.W. K.W. L.K.V. and R.W.S.; project administration: T.G.C. M.M.-R. K.W. L.K.V. and R.W.S.; supervision: C.L. D.M. G.O. A.B.W. M.C. J.P.M. P.J.K. B.F.H. I.A.W. K.W. L.K.V. and R.W.S.; writing – original draft: T.G.C. L.K.V. and R.W.S.; review and editing: all authors. Amsterdam UMC has filed a patent application related to germline-targeting HIV-1 Env trimers. Publisher Copyright: © 2023 The Author(s)
PY - 2023/4/18
Y1 - 2023/4/18
N2 - Targeting germline (gl-) precursors of broadly neutralizing antibodies (bNAbs) is acknowledged as an important strategy for HIV-1 vaccines. The VRC01-class of bNAbs is attractive because of its distinct genetic signature. However, VRC01-class bNAbs often require extensive somatic hypermutation, including rare insertions and deletions. We describe a BG505 SOSIP trimer, termed GT1.2, to optimize binding to gl-CH31, the unmutated common precursor of the CH30-34 bNAb lineage that acquired a large CDRH1 insertion. The GT1.2 trimer activates gl-CH31 naive B cells in knock-in mice, and B cell responses could be matured by selected boosting immunogens to generate cross-reactive Ab responses. Next-generation B cell sequencing reveals selection for VRC01-class mutations, including insertions in CDRH1 and FWR3 at positions identical to VRC01-class bNAbs, as well as CDRL1 deletions and/or glycine substitutions to accommodate the N276 glycan. These results provide proof of concept for vaccine-induced affinity maturation of B cell lineages that require rare insertions and deletions.
AB - Targeting germline (gl-) precursors of broadly neutralizing antibodies (bNAbs) is acknowledged as an important strategy for HIV-1 vaccines. The VRC01-class of bNAbs is attractive because of its distinct genetic signature. However, VRC01-class bNAbs often require extensive somatic hypermutation, including rare insertions and deletions. We describe a BG505 SOSIP trimer, termed GT1.2, to optimize binding to gl-CH31, the unmutated common precursor of the CH30-34 bNAb lineage that acquired a large CDRH1 insertion. The GT1.2 trimer activates gl-CH31 naive B cells in knock-in mice, and B cell responses could be matured by selected boosting immunogens to generate cross-reactive Ab responses. Next-generation B cell sequencing reveals selection for VRC01-class mutations, including insertions in CDRH1 and FWR3 at positions identical to VRC01-class bNAbs, as well as CDRL1 deletions and/or glycine substitutions to accommodate the N276 glycan. These results provide proof of concept for vaccine-induced affinity maturation of B cell lineages that require rare insertions and deletions.
KW - HIV-1 Env
KW - NGS
KW - bNAbs
KW - deletions
KW - germline-targeting
KW - insertions
KW - mouse model
KW - neutralizing antibodies
KW - vaccines
UR - http://www.scopus.com/inward/record.url?scp=85152368267&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.xcrm.2023.101003
DO - https://doi.org/10.1016/j.xcrm.2023.101003
M3 - Article
C2 - 37044090
SN - 2666-3791
VL - 4
JO - Cell Reports Medicine
JF - Cell Reports Medicine
IS - 4
M1 - 101003
ER -