Download MendeleyHIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen.
Jardine, J.G., Kulp, D.W., 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, A.C., Julien, J.P., Wilson, I.A., Burton, D.R., Crotty, S., Schief, W.R.(2016) Science 351: 1458-1463
- PubMed: 27013733
- DOI: https://doi.org/10.1126/science.aad9195
- Primary Citation of Related Structures:
5IFA - PubMed Abstract:
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.
Organizational Affiliation:
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
