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Publication Abstract from PubMed

Induction of broadly neutralizing antibodies (bnAbs) is a major HIV vaccine goal. Germline-targeting immunogens aim to initiate bnAb induction by activating bnAb germline precursor B cells. Critical unmet challenges are to determine whether bnAb precursor naive B cells bind germline-targeting immunogens and occur at sufficient frequency in humans for reliable vaccine responses. Using deep mutational scanning and multitarget optimization, we developed a germline-targeting immunogen (eOD-GT8) for diverse VRC01-class bnAbs. We then used the immunogen to isolate VRC01-class precursor naive B cells from HIV-uninfected donors. Frequencies of true VRC01-class precursors, their structures, and their eOD-GT8 affinities support this immunogen as a candidate human vaccine prime. These methods could be applied to germline targeting for other classes of HIV bnAbs and for Abs to other pathogens.

HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen.,Jardine JG, Kulp DW, Havenar-Daughton C, Sarkar A, Briney B, Sok D, Sesterhenn F, Ereno-Orbea J, Kalyuzhniy O, Deresa I, Hu X, Spencer S, Jones M, Georgeson E, Adachi Y, Kubitz M, deCamp AC, Julien JP, Wilson IA, Burton DR, Crotty S, Schief WR Science. 2016 Mar 25;351(6280):1458-63. doi: 10.1126/science.aad9195. PMID:27013733^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.