Mapping Polyclonal Antibody Responses in Non-human Primates Vaccinated with HIV Env Trimer Subunit Vaccines

Cell Rep. 2020 Mar 17;30(11):3755-3765.e7. doi: 10.1016/j.celrep.2020.02.061.


Rational immunogen design aims to focus antibody responses to vulnerable sites on primary antigens. Given the size of these antigens, there is, however, potential for eliciting unwanted, off-target responses. Here, we use our electron microscopy polyclonal epitope mapping approach to describe the antibody specificities elicited by immunization of non-human primates with soluble HIV envelope trimers and subsequent repeated viral challenge. An increased diversity of epitopes recognized and the approach angle by which these antibodies bind constitute a hallmark of the humoral response in most protected animals. We also show that fusion peptide-specific antibodies are likely responsible for some neutralization breadth. Moreover, cryoelectron microscopy (cryo-EM) analysis of a fully protected animal reveals a high degree of clonality within a subset of putatively neutralizing antibodies, enabling a detailed molecular description of the antibody paratope. Our results provide important insights into the immune response against a vaccine candidate that entered into clinical trials in 2019.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibody Formation / immunology*
  • Cross Reactions / immunology
  • Cryoelectron Microscopy
  • Epitopes / chemistry
  • Epitopes / immunology
  • HEK293 Cells
  • HIV Antibodies / chemistry
  • HIV Antibodies / immunology*
  • Humans
  • Immunity, Humoral
  • Macaca mulatta
  • Models, Molecular
  • Protein Multimerization*
  • Vaccination*
  • Vaccines, Subunit / immunology*
  • env Gene Products, Human Immunodeficiency Virus / immunology*


  • Antibodies, Neutralizing
  • Epitopes
  • HIV Antibodies
  • Vaccines, Subunit
  • env Gene Products, Human Immunodeficiency Virus