HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen

• Autores: Joseph G. Jardine, Daniel W. Kulp, Colin Havenar Daughton, Anita Sarkar
• Localización: Science, ISSN 0036-8075, Vol. 351, Nº 6280, 2016, págs. 1458-1463
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • 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.