Immune Monitoring Reveals Fusion Peptide Priming to Imprint Cross-Clade HIV-Neutralizing Responses with a Characteristic Early B Cell Signature

Cell Rep. 2020 Aug 4;32(5):107981. doi: 10.1016/j.celrep.2020.107981.


The HIV fusion peptide (FP) is a promising vaccine target. FP-directed monoclonal antibodies from vaccinated macaques have been identified that neutralize up to ∼60% of HIV strains; these vaccinations, however, have involved ∼1 year with an extended neutralization-eclipse phase without measurable serum neutralization. Here, in 32 macaques, we test seven vaccination regimens, each comprising multiple immunizations of FP-carrier conjugates and HIV envelope (Env) trimers. Comparisons of vaccine regimens reveal FP-carrier conjugates to imprint cross-clade neutralizing responses and a cocktail of FP conjugate and Env trimer to elicit the earliest broad responses. We identify a signature, appearing as early as week 6 and involving the frequency of B cells recognizing both FP and Env trimer, predictive of vaccine-elicited breadth ∼1 year later. Immune monitoring of B cells in response to vaccination can thus enable vaccine insights even in the absence of serum neutralization, here identifying FP imprinting, cocktail approach, and early signature as means to improve FP-directed vaccine responses.

Keywords: HIV vaccine; NHP; early signature; envelope trimer; fusion peptide; immune monitoring; immunization regimen; immunogen cocktail; imprinting; prime-boost immunization.

Publication types

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

MeSH terms

  • AIDS Vaccines / immunology
  • Animals
  • Antibodies, Neutralizing / immunology*
  • B-Lymphocytes / immunology*
  • HIV Antibodies / immunology*
  • HIV Antigens / immunology
  • HIV Infections / immunology
  • Hemocyanins / metabolism
  • Immunization
  • Macaca mulatta
  • Male
  • Monitoring, Immunologic*
  • Peptides / immunology*
  • Polysaccharides / metabolism
  • Protein Multimerization
  • Recombinant Fusion Proteins / immunology*
  • env Gene Products, Human Immunodeficiency Virus / immunology


  • AIDS Vaccines
  • Antibodies, Neutralizing
  • HIV Antibodies
  • HIV Antigens
  • Peptides
  • Polysaccharides
  • Recombinant Fusion Proteins
  • env Gene Products, Human Immunodeficiency Virus
  • Hemocyanins
  • keyhole-limpet hemocyanin