HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies
Name
Irvine_HIV vaccine.pdf
Size
2.65 MB
Format
Adobe PDF
Checksum (MD5)
f4ee2f67c25921574df5584bbccb18e1
Author(s)
Steichen, Jon M.
Kulp, Daniel W.
Escolano, Amelia
Dosenovic, Pia
Stanfield, Robyn L.
McCoy, Laura E.
Ozorowski, Gabriel
Hu, Xiaozhen
Kalyuzhniy, Oleksandr
Briney, Bryan
Date Issued
September 2016
Journal
Immunity
Publisher
Elsevier
Citation
Steichen, Jon M., Daniel W. Kulp, Talar Tokatlian, Amelia Escolano, Pia Dosenovic, Robyn L. Stanfield, Laura E. McCoy, et al. “HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies.” Immunity 45, no. 3 (September 2016): 483–496.
Version
Final published version
Abstract
Broadly neutralizing antibodies (bnAbs) against the N332 supersite of the HIV envelope (Env) trimer are the most common bnAbs induced during infection, making them promising leads for vaccine design. Wild-type Env glycoproteins lack detectable affinity for supersite-bnAb germline precursors and are therefore unsuitable immunogens to prime supersite-bnAb responses. We employed mammalian cell surface display to design stabilized Env trimers with affinity for germline-reverted precursors of PGT121-class supersite bnAbs. The trimers maintained native-like antigenicity and structure, activated PGT121 inferred-germline B cells ex vivo when multimerized on liposomes, and primed PGT121-like responses in PGT121 inferred-germline knockin mice. Design intermediates have levels of epitope modification between wild-type and germline-targeting trimers; their mutation gradient suggests sequential immunization to induce bnAbs, in which the germline-targeting prime is followed by progressively less-mutated design intermediates and, lastly, with native trimers. The vaccine design strategies described could be utilized to target other epitopes on HIV or other pathogens.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution 4.0 International License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.immuni.2016.08.016
