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Germline-targeting HIV-1 Env vaccination induces VRC01-class antibodies with rare insertions.

Publication ,  Journal Article
Caniels, TG; Medina-Ramírez, M; Zhang, J; Sarkar, A; Kumar, S; LaBranche, A; Derking, R; Allen, JD; Snitselaar, JL; Capella-Pujol, J; Diaz, M ...
Published in: Cell Rep Med
April 18, 2023

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.

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Published In

Cell Rep Med

DOI

EISSN

2666-3791

Publication Date

April 18, 2023

Volume

4

Issue

4

Start / End Page

101003

Location

United States

Related Subject Headings

  • Vaccination
  • Mice
  • HIV-1
  • HIV Seropositivity
  • HIV Antibodies
  • Broadly Neutralizing Antibodies
  • Antibodies, Neutralizing
  • Animals
  • 32 Biomedical and clinical sciences
 

Citation

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Caniels, T. G., Medina-Ramírez, M., Zhang, J., Sarkar, A., Kumar, S., LaBranche, A., … Sanders, R. W. (2023). Germline-targeting HIV-1 Env vaccination induces VRC01-class antibodies with rare insertions. Cell Rep Med, 4(4), 101003. https://doi.org/10.1016/j.xcrm.2023.101003
Caniels, Tom G., Max Medina-Ramírez, Jinsong Zhang, Anita Sarkar, Sonu Kumar, Alex LaBranche, Ronald Derking, et al. “Germline-targeting HIV-1 Env vaccination induces VRC01-class antibodies with rare insertions.Cell Rep Med 4, no. 4 (April 18, 2023): 101003. https://doi.org/10.1016/j.xcrm.2023.101003.
Caniels TG, Medina-Ramírez M, Zhang J, Sarkar A, Kumar S, LaBranche A, et al. Germline-targeting HIV-1 Env vaccination induces VRC01-class antibodies with rare insertions. Cell Rep Med. 2023 Apr 18;4(4):101003.
Caniels, Tom G., et al. “Germline-targeting HIV-1 Env vaccination induces VRC01-class antibodies with rare insertions.Cell Rep Med, vol. 4, no. 4, Apr. 2023, p. 101003. Pubmed, doi:10.1016/j.xcrm.2023.101003.
Caniels TG, Medina-Ramírez M, Zhang J, Sarkar A, Kumar S, LaBranche A, Derking R, Allen JD, Snitselaar JL, Capella-Pujol J, Sánchez IDM, Yasmeen A, Diaz M, Aldon Y, Bijl TPL, Venkatayogi S, Martin Beem JS, Newman A, Jiang C, Lee W-H, Pater M, Burger JA, van Breemen MJ, de Taeye SW, Rantalainen K, LaBranche C, Saunders KO, Montefiori D, Ozorowski G, Ward AB, Crispin M, Moore JP, Klasse PJ, Haynes BF, Wilson IA, Wiehe K, Verkoczy L, Sanders RW. Germline-targeting HIV-1 Env vaccination induces VRC01-class antibodies with rare insertions. Cell Rep Med. 2023 Apr 18;4(4):101003.

Published In

Cell Rep Med

DOI

EISSN

2666-3791

Publication Date

April 18, 2023

Volume

4

Issue

4

Start / End Page

101003

Location

United States

Related Subject Headings

  • Vaccination
  • Mice
  • HIV-1
  • HIV Seropositivity
  • HIV Antibodies
  • Broadly Neutralizing Antibodies
  • Antibodies, Neutralizing
  • Animals
  • 32 Biomedical and clinical sciences