HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies

Steichen, Jon M.; Kulp, Daniel W.; Tokatlian, Talar; Escolano, Amelia; Dosenovic, Pia; Stanfield, Robyn L.; McCoy, Laura E.; Ozorowski, Gabriel; Hu, Xiaozhen; Kalyuzhniy, Oleksandr; Briney, Bryan; Schiffner, Torben; Garces, Fernando; Freund, Natalia T.; Gitlin, Alexander D.; Menis, Sergey; Georgeson, Erik; Kubitz, Michael; Adachi, Yumiko; Jones, Meaghan; Mutafyan, Andrew A.; Yun, Dong Soo; Mayer, Christian T.; Ward, Andrew B.; Burton, Dennis R.; Wilson, Ian A.; Irvine, Darrell J.; Nussenzweig, Michel C.; Schief, William R.

doi:10.1016/j.immuni.2016.08.016

Title: HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies

Journal Article · Thu Sep 01 00:00:00 EDT 2016 · Immunity

DOI:https://doi.org/10.1016/j.immuni.2016.08.016· OSTI ID:1392745

Steichen, Jon M.; Kulp, Daniel W.; Tokatlian, Talar; Escolano, Amelia; Dosenovic, Pia; Stanfield, Robyn L.; McCoy, Laura E.; Ozorowski, Gabriel; Hu, Xiaozhen; Kalyuzhniy, Oleksandr; Briney, Bryan; Schiffner, Torben; Garces, Fernando; Freund, Natalia T.; Gitlin, Alexander D.; Menis, Sergey; Georgeson, Erik; Kubitz, Michael; Adachi, Yumiko; Jones, Meaghan more »

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.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER); National Inst. of Allergy and Infectious Diseases; Internation AIDS Vaccine Initiative (IAVI)

Grant/Contract Number:: CHAVI-ID 1UM1AI100663; P01 AI110657; R01 AI084817; P41GM103393

OSTI ID:: 1392745

Alternate ID(s):: OSTI ID: 1368235

Journal Information:: Immunity, Journal Name: Immunity Vol. 45 Journal Issue: 3; ISSN 1074-7613

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 241 works

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