PXD075109

PXD075109 is an original dataset announced via ProteomeXchange.

Title	Vaccination elicits HIV broadly neutralizing antibodies in nonhuman primates
Description	The high antigenic diversity of HIV has been a major obstacle to development of a broadly protective vaccine. Nevertheless, protective HIV broadly neutralizing antibodies (bnAbs) exist and have been proposed as templates for vaccine development1-6. Germline-targeting is a conceptually radical vaccine design approach to elicit bnAbs, aiming to prime rare bnAb-precursor B cells possessing pre-determined human genetic and structural features shared with template bnAbs, and then guide B cell affinity maturation to potent bnAb evolution with heterologous boosters7-11. Although the approach has shown promise in clinical12-17 and pre-clinical18-34 studies, it faces many immunological challenges and, to date, has not succeeded in generating bnAbs in humans or nontransgenic animals. Here, we report a germline-targeting vaccine tested in outbred nonhuman primates that successfully generated bnAb-class memory B cells and sera capable of neutralizing diverse HIV clinical isolates. bnAb clonal lineages were generated in 50% or more of animals, achieving up to 46% neutralization breadth compared to the reference bnAb. Vaccine-induced bnAbs exhibited precise structural mimicry of human bnAb interactions with HIV envelope (Env), matching the germline-targeting predictions. Furthermore, serum bnAb activity developed in 44% of animals; in the most striking instance serum bnAb titers reached levels expected to confer protection against diverse HIV isolates. These results demonstrate proof of principle that germline-targeting vaccines can reproducibly elicit prespecified classes of bnAbs to prespecified epitopes under endogenous conditions, supporting further optimization of this approach for HIV vaccine development. Simultaneously, these results also demonstrate fundamental immunological findings, including that exceptionally rare B cells can be primed and recruited into germinal centers, competitive within germinal centers, affinity matured for extended periods, differentiated into memory B cells, boosted repeatedly with new immunogens, and differentiated into large numbers of bnAb plasma cells.
HostingRepository	MassIVE
AnnounceDate	2026-06-29
AnnouncementXML	Submission_2026-06-29_16:52:16.646.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sabyasachi Baboo
SpeciesList	scientific name: Human immunodeficiency virus 1; NCBI TaxID: 11676; scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	HexNAc; Deamidated:18O(1); Oxidation; 2-pyrrolidone-5-carboxylic acid (Gln)
Instrument	Q Exactive HF-X; Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-02 15:31:13	ID requested
⏵ 1	2026-06-29 16:52:17	announced

no publication

submitter keyword: HIV, Env, nonhuman primate, germline targeting vaccine, broadly neutralizing antibody (bnAb), DeGlyPHER, site-specific N-glycan analysis, DatasetType:Proteomics

John R. Yates III
contact affiliation	The Scripps Research Institute
contact email	jyates@scripps.edu
lab head
Sabyasachi Baboo
contact affiliation	The Scripps Research Institute, La Jolla, CA
contact email	sbaboo@scripps.edu
dataset submitter

MassIVE dataset URI

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