@article{TEXTUAL,
      recid = {6855},
      author = {Jardine, Joseph G. and Sok, Devin and Julien,  Jean-Philippe and Briney, Bryan and Sarkar, Anita and  Liang, Chi-Hui and Scherer, Erin A. and Henry Dunand,  Carole J. and Adachi, Yumiko and Adachi, Yumiko and  Diwanji, Devan and Hsueh, Jessica and Jones, Meaghan and  Kalyuzhniy, Oleksandr and Kubitz, Michael and Spencer, Skye  and Pauthner, Matthias and Saye-Francisco, Karen L. and  Sesterhenn, Fabian and Wilson, Patrick C. and Galloway,  Denise M. and Stanfield, Robyn L. and Wilson, Ian A. and  Burton, Dennis R. and Schief, William R.},
      title = {Minimally Mutated HIV-1 Broadly Neutralizing Antibodies to  Guide Reductionist Vaccine Design},
      journal = {PLOS Pathogens},
      address = {2016-08-25},
      number = {TEXTUAL},
      abstract = {An optimal HIV vaccine should induce broadly neutralizing  antibodies (bnAbs) that neutralize diverse viral strains  and subtypes. However, potent bnAbs develop in only a small  fraction of HIV-infected individuals, all contain rare  features such as extensive mutation, insertions, deletions,  and/or long complementarity-determining regions, and some  are polyreactive, casting doubt on whether bnAbs to HIV can  be reliably induced by vaccination. We engineered two  potent VRC01-class bnAbs that minimized rare features.  According to a quantitative features frequency analysis,  the set of features for one of these minimally mutated  bnAbs compared favorably with all 68 HIV bnAbs analyzed and  was similar to antibodies elicited by common vaccines. This  same minimally mutated bnAb lacked polyreactivity in four  different assays. We then divided the minimal mutations  into spatial clusters and dissected the epitope components  interacting with those clusters, by mutational and  crystallographic analyses coupled with neutralization  assays. Finally, by synthesizing available data, we  developed a working-concept boosting strategy to select the  mutation clusters in a logical order following a  germline-targeting prime. We have thus developed potent HIV  bnAbs that may be more tractable vaccine goals compared to  existing bnAbs, and we have proposed a strategy to elicit  them. This reductionist approach to vaccine design, guided  by antibody and antigen structure, could be applied to  design candidate vaccines for other HIV bnAbs or protective  Abs against other pathogens.},
      url = {http://knowledge.uchicago.edu/record/6855},
}