GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE326nnn/GSE326649/primary200OKOtherMacaca mulatta Expression profiling by high throughput sequencingOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE326649GEOGSEfalseVaccination elicits HIV broadly neutralizing antibodies in primatesThe 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 an adjuvanted protein 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% 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.2026/06/24GSE326649GSM9636339GSM9636453GSM9636332GSM9636452GSM9636331GSM9636334GSM9636455GSM9636454GSM9636333GSM9636457GSM9636336GSM9636456GSM9636335GSM9636459GSM9636338GSM9636337GSM9636458GSM9636451GSM9636330GSM9636450GSM9636343GSM9636464GSM9636342GSM9636463GSM9636345GSM9636466GSM9636465GSM9636344GSM9636468GSM9636347GSM9636346GSM9636467GSM9636349GSM9636348GSM9636469GSM9636460GSM9636462GSM9636341GSM9636340GSM9636461GSM9785375GSM9785376GSM9785377GSM9636475GSM9636354GSM9636474GSM9636353GSM9636477GSM9636356GSM9636355GSM9636476GSM9636358GSM9785378GSM9785379GSM9636478GSM9636357GSM9636359GSM9636471GSM9636350GSM9636470GSM9636352GSM9636473GSM9636472GSM9636351GSM9785385GSM9636406GSM9636405GSM9785386GSM9785387GSM9636408GSM9785388GSM9636407GSM9785381GSM9785382GSM9636409GSM9785383GSM9785384GSM9636365GSM9636364GSM9636400GSM9636367GSM9636366GSM9636402GSM9636369GSM9785389GSM9636368GSM9636401GSM9636404GSM9636403GSM9636361GSM9636360GSM9636363GSM9636362GSM9785380GSM9636417GSM9636416GSM9636419GSM9636418GSM9785392GSM9636376GSM9636375GSM9636411GSM9636378GSM9636410GSM9636377GSM9636413GSM9636379GSM9636412GSM9636415GSM9636414GSM9636370GSM9636372GSM9636371GSM9636374GSM9636373GSM9785390GSM9785391GSM9636428GSM9636427GSM9636309GSM9636308GSM9636429GSM9636420GSM9636387GSM9636386GSM9636389GSM9636422GSM9636388GSM9636421GSM9636424GSM9636423GSM9636426GSM9636425GSM9636381GSM9636380GSM9636383GSM9636382GSM9636385GSM9636384GSM9636439GSM9636318GSM9636317GSM9636438GSM9636319GSM9636398GSM9636431GSM9636310GSM9636397GSM9636430GSM9636433GSM9636312GSM9636311GSM9636432GSM9636399GSM9636314GSM9636435GSM9636434GSM9636313GSM9636437GSM9636316GSM9636436GSM9636315GSM9636390GSM9636392GSM9636391GSM9636394GSM9636393GSM9636396GSM9636395GSM9636329GSM9636449GSM9636328GSM9636321GSM9636442GSM9636320GSM9636441GSM9636323GSM9636444GSM9636443GSM9636322GSM9636446GSM9636325GSM9636445GSM9636324GSM9636448GSM9636327GSM9636326GSM9636447GSM963644027943326649Macaca mulatta