|Title||HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Jardine JG, Kulp DW, Havenar-Daughton C, Sarkar A, Briney B, Sok D, Sesterhenn F, Ereño-Orbea J, Kalyuzhniy O, Deresa I, Hu X, Spencer S, Jones M, Georgeson E, Adachi Y, Kubitz M, DeCamp AC, Julien J-P, Wilson IA, Burton DR, Crotty S, Schief WR|
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 naïve 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 naïve 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.
|Grant List||P01 AI094419 / AI / NIAID NIH HHS / United States |
P01 AI110657 / AI / NIAID NIH HHS / United States
P41GM103393 / GM / NIGMS NIH HHS / United States
R01 AI084817 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen.