title: Development of broadly neutralizing antibodies from autologous neutralizing antibody responses in HIV infection.
abstract: OBJECTIVE
  Detailed genetic and structural characterization has revealed that broadly neutralizing antibodies (bnAbs) against HIV-1 have unusually high levels of somatic hypermutation, long CDRH3 domains, and the ability to target one of four sites of vulnerability on the HIV-1 envelope (Env) glycoproteins. A current priority is to understand how bnAbs are generated during natural infection, and translate this information into immunogens that can elicit bnAb following vaccination.
  
  
  RESULTS
  Strain-specific neutralizing antibodies can acquire broad neutralizing capacity when the transmitted/founder Env or a specific Env variant is recognized by an unmutated rearranged germline that has the capacity to develop bnAb-like features. This event could be relatively infrequent, as only certain germlines appear to possess inherent features needed for bnAb activity. Furthermore, the glycosylation pattern and diversity of circulating HIV-1 Envs, as well as the state of the B-cell compartment, may influence the activation and maturation of certain antibody lineages.
  
  
  CONCLUSIONS
  Collectively, studies over the last year have suggested that the development of HIV-1 Env immunogens that bind and activate bnAb-like germlines is feasible. However, more information about the features of Env variants and the host factors that lead to breadth during natural infection are needed to elicit bnAbs through immunization.
authors.affiliation: aEmory Vaccine Center at Yerkes National Primate Research Center bDepartment of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA cCentre for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Services dUniversity of the Witwatersrand, Johannesburg eCenter for the AIDS Program of Research (CAPRISA), South Africa.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Derdeyn
authors.forename: Penny L
authors.initials: PL
authors.lastname: Moore
authors.forename: Lynn
authors.initials: L
authors.lastname: Morris
mesh_terms: D057134:Antibodies, Neutralizing / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015483:HIV Antibodies / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus