Antibody Lineages with Vaccine-Induced Antigen-Binding Hotspots Develop Broad HIV Neutralization

Cell. 2019 Jul 25;178(3):567-584.e19. doi: 10.1016/j.cell.2019.06.030.


The vaccine-mediated elicitation of antibodies (Abs) capable of neutralizing diverse HIV-1 strains has been a long-standing goal. To understand how broadly neutralizing antibodies (bNAbs) can be elicited, we identified, characterized, and tracked five neutralizing Ab lineages targeting the HIV-1-fusion peptide (FP) in vaccinated macaques over time. Genetic and structural analyses revealed two of these lineages to belong to a reproducible class capable of neutralizing up to 59% of 208 diverse viral strains. B cell analysis indicated each of the five lineages to have been initiated and expanded by FP-carrier priming, with envelope (Env)-trimer boosts inducing cross-reactive neutralization. These Abs had binding-energy hotspots focused on FP, whereas several FP-directed Abs induced by immunization with Env trimer-only were less FP-focused and less broadly neutralizing. Priming with a conserved subregion, such as FP, can thus induce Abs with binding-energy hotspots coincident with the target subregion and capable of broad neutralization.

Keywords: B cell ontogeny; HIV-1 vaccine; broadly neutralizing antibody; fusion peptide; immune monitoring; interaction hotspot; multidonor antibody class.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • AIDS Vaccines / immunology*
  • Amino Acid Sequence
  • Animals
  • Antibodies, Neutralizing / chemistry
  • Antibodies, Neutralizing / classification
  • Antibodies, Neutralizing / immunology*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism
  • Crystallography, X-Ray
  • Female
  • HEK293 Cells
  • HIV Antibodies / chemistry
  • HIV Antibodies / classification
  • HIV Antibodies / immunology*
  • HIV-1 / metabolism
  • Humans
  • Macaca mulatta
  • Male
  • Peptides / chemistry
  • Peptides / immunology*
  • Protein Structure, Tertiary
  • env Gene Products, Human Immunodeficiency Virus / chemistry
  • env Gene Products, Human Immunodeficiency Virus / immunology
  • env Gene Products, Human Immunodeficiency Virus / metabolism


  • AIDS Vaccines
  • Antibodies, Neutralizing
  • HIV Antibodies
  • Peptides
  • env Gene Products, Human Immunodeficiency Virus