PXD015168-1

PXD015168 is an original dataset announced via ProteomeXchange.

Title	Overcoming steric restrictions of VRC01 HIV-1 neutralizing antibodies through immunization
Description	Broadly HIV-1 neutralizing VRC01-class antibodies target the CD4-binding site of Env. They are derived from VH1-2*02 antibody heavy chains paired with rare light chains expressing five amino acid long CDRL3s. They have been isolated from infected subjects but have not yet been elicited by immunization. Env-derived immunogens capable of binding the germline forms of VRC01 B cell receptors on naïve B cells have been designed and evaluated in knock-in mice. However, the elicited antibodies cannot bypass glycans present on the conserved position N276 of Env, which restricts access to the CD4-binding site. Efforts to guide the appropriate maturation of these antibodies by sequential immunization have not yet been successful. Here, we report on a two-step immunization scheme that led to the maturation of VRC01-like antibodies capable of accommodating the N276 glycan and displaying autologous tier 2 neutralizing activities. Our results are relevant to clinical trials aiming to elicit VRC01 antibodies.
HostingRepository	PRIDE
AnnounceDate	2020-05-26
AnnouncementXML	Submission_2020-05-26_15:01:44.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD015168
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Andrew Borst
SpeciesList	scientific name: Human immunodeficiency virus 1; NCBI TaxID: 11676;
ModificationList	Carboxymethyl; Oxidation
Instrument	Orbitrap Fusion ETD

Revision	Datetime	Status	ChangeLog Entry
0	2019-08-27 05:51:55	ID requested
⏵ 1	2020-05-26 15:01:45	announced

Parks KR, MacCamy AJ, Trichka J, Gray M, Weidle C, Borst AJ, Khechaduri A, Takushi B, Agrawal P, Guenaga J, Wyatt RT, Coler R, Seaman M, LaBranche C, Montefiori DC, Veesler D, Pancera M, McGuire A, Stamatatos L, Overcoming Steric Restrictions of VRC01 HIV-1 Neutralizing Antibodies through Immunization. Cell Rep, 29(10):3060-3072.e7(2019) [pubmed]

submitter keyword: HIV, Glycan, N276, bNAb, VRC01, Antibody, Immunization, 426c core, Mice

David Veesler
contact affiliation	Assistant Professor, Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA
contact email	dveesler@uw.edu
lab head
Andrew Borst
contact affiliation	University of Washington
contact email	borsta2@uw.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD015168
     1. Label: PRIDE project
     2. Name: Overcoming steric restrictions of VRC01 HIV-1 neutralizing antibodies through immunization