PXD033766-1

PXD033766 is an original dataset announced via ProteomeXchange.

Title	Human Immunoglobulin Repertoire-Guided Immunogen Design Targeting HIV V2-Apex Broadly Neutralizing Antibody Precursors
Description	Broadly neutralizing antibodies (bnAbs) to the HIV envelope (Env) V2-apex region are important leads for HIV vaccine design. Most V2-apex bnAbs engage Env with an uncommonly long heavy chain complementarity-determining region 3 (HCDR3), suggesting that rarity of bnAb precursors poses a challenge for vaccine priming. We created precursor sequence definitions for V2-apex HCDR3-dependent bnAbs and searched for related precursors in human antibody heavy chain ultradeep sequencing data from 14 HIV-unexposed donors. We found potential precursors in a majority of donors for only two long-HCDR3 V2-apex bnAbs, PCT64 and PG9, identifying these bnAbs as priority vaccine targets. We then engineered ApexGT Env trimers that bind inferred germlines for PCT64 and PG9 and have higher affinities for bnAbs; determined cryo-EM structures of ApexGT trimers bound to inferred germline and bnAb forms of PCT64 and PG9; and developed an mRNA-encoded cell-surface trimer for our lead ApexGT candidate. The methods and immunogens developed here have promise to assist the development of an HIV vaccine.
HostingRepository	PRIDE
AnnounceDate	2023-03-11
AnnouncementXML	Submission_2023-03-11_06:02:34.869.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD033766
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	SabyasachiBaboo
SpeciesList	scientific name: Human immunodeficiency virus; NCBI TaxID: NCBITaxon:12721; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	N-acetylhexosaminylated residue; 2-pyrrolidone-5-carboxylic acid (Gln); monohydroxylated residue; 1x(18)O labeled deamidated L-asparagine
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-08 04:16:29	ID requested
⏵ 1	2023-03-11 06:02:35	announced
2	2023-11-14 08:43:15	announced	2023-11-14: Updated project metadata.

10.6019/PXD033766;

Willis JR, Berndsen ZT, Ma KM, Steichen JM, Schiffner T, Landais E, Liguori A, Kalyuzhniy O, Allen JD, Baboo S, Omorodion O, Diedrich JK, Hu X, Georgeson E, Phelps N, Eskandarzadeh S, Groschel B, Kubitz M, Adachi Y, Mullin TM, Alavi NB, Falcone S, Himansu S, Carfi A, Wilson IA, Yates JR, Paulson JC, Crispin M, Ward AB, Schief WR, Human immunoglobulin repertoire analysis guides design of vaccine priming immunogens targeting HIV V2-apex broadly neutralizing antibody precursors. Immunity, 55(11):2149-2167.e9(2022) [pubmed]

submitter keyword: HIV Antibodies,AIDS Vaccines, Structural Vaccinology, Immunoinformatics

John R. YatesIII
contact affiliation	Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California 92037 United States
contact email	jyates@scripps.edu
lab head
SabyasachiBaboo
contact affiliation	The Scripps Research Institute, La Jolla, California
contact email	sbaboo@scripps.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/03/PXD033766

PRIDE project URI

• PRIDE
  1. PXD033766
     1. Label: PRIDE project
     2. Name: Human Immunoglobulin Repertoire-Guided Immunogen Design Targeting HIV V2-Apex Broadly Neutralizing Antibody Precursors