Human immunoglobulin repertoire analysis guides design of vaccine priming immunogens targeting HIV V2-apex broadly neutralizing antibody precursors

Accepted/In Press date: 31 August 2022

e-pub ahead of print date: 29 September 2022

Published date: 8 November 2022

Additional Information: This work was supported by the IAVI Neutralizing Antibody Center through the Collaboration for AIDS Vaccine Discovery grants OPP1084519 , OPP1196345 / INV-008813 , OPP1147787 , and INV-034657 funded by the Bill and Melinda Gates Foundation (to M.C., I.A.W., A.B.W., and W.R.S.), National Institute of Allergy and Infectious Diseases ( NIAID ) UM1 Al100663 ( Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery), and UM1 AI144462 ( Scripps Consortium for HIV/AIDS Vaccine Development) (to I.A.W., A.B.W., and W.R.S.) and by the Ragon Institute of MGH, MIT, and Harvard (to W.R.S.). Funding Information: This work was supported by the IAVI Neutralizing Antibody Center through the Collaboration for AIDS Vaccine Discovery grants OPP1084519, OPP1196345/INV-008813, OPP1147787, and INV-034657 funded by the Bill and Melinda Gates Foundation (to M.C. I.A.W. A.B.W. and W.R.S.), National Institute of Allergy and Infectious Diseases (NIAID) UM1 Al100663 (Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery), and UM1 AI144462 (Scripps Consortium for HIV/AIDS Vaccine Development) (to I.A.W. A.B.W. and W.R.S.) and by the Ragon Institute of MGH, MIT, and Harvard (to W.R.S.). J.R.W. and K.M.M. designed ApexGT immunogens. Z.T.B. conducted EM studies. J.M.S. assisted ApexGT immunogen design and, with T.S. developed the MD39 gp151 immunogen platform. J.R.W. wrote bioinformatic applications and conducted precursor frequency analysis. E.L. provided information about the PCT64 lineage prior to its original publication. A.L. conducted ELISA studies. O.K. conducted surface plasmon resonance (SPR) studies. J.D.A. S.B. and J.K.D. conducted mass-spec glycan profiling studies. O.O. solved the crystal structure of apo PCT64 LMCA. X.H. conducted differential scanning calorimetry (DSC) and size-exclusion chromatography with multi-angle light scattering (SECMALS) studies. S.E. and K.M.M. conducted the cell surface antigenic profiling studies. E.G. N.P. S.E. M.K. Y.A. T.-M.M. and N.B.A. produced all proteins, antibodies, and Fabs for all reported studies. B.G. supervised reagent production. S.F. S.H. and A.C. provided mRNA. I.A.W. supervised crystal structure determination. J.R.Y. J.C.P. and M.C. supervised glycan profiling. A.B.W. supervised ns- and cryo-EM studies. W.R.S. conceived the studies with J.R.W. K.M.M. and J.M.S. and W.R.S. supervised the studies. J.R.W. Z.T.B. and W.R.S. wrote the paper. K.M.M. J.M.S. S.H. A.C. and A.B.W. helped write the paper. J.R.W. K.M.M. J.M.S. and W.R.S. are named inventors on patent applications filed by Scripps and IAVI regarding ApexGT immunogens in this manuscript. Publisher Copyright: © 2022 The Author(s)

Local EPrints ID: 472336

URI: http://eprints.soton.ac.uk/id/eprint/472336

DOI: doi:10.1016/j.immuni.2022.09.001

ISSN: 1097-4180

PURE UUID: 4530aab9-fe13-4cb4-bf56-e75bde8e7c4e

ORCID for Joel D Allen: orcid.org/0000-0003-2547-968X

ORCID for Max Crispin: orcid.org/0000-0002-1072-2694

Date deposited: 01 Dec 2022 17:49

Last modified: 17 Mar 2024 04:09