Anti-idiotypic antibodies elicit anti-HIV-1-specific B cell responses

J Exp Med. 2019 Oct 7;216(10):2316-2330. doi: 10.1084/jem.20190446. Epub 2019 Jul 25.


Human anti-HIV-1 broadly neutralizing antibodies (bNAbs) protect against infection in animal models. However, bNAbs have not been elicited by vaccination in diverse wild-type animals or humans, in part because B cells expressing the precursors of these antibodies do not recognize most HIV-1 envelopes (Envs). Immunogens have been designed that activate these B cell precursors in vivo, but they also activate competing off-target responses. Here we report on a complementary approach to expand specific B cells using an anti-idiotypic antibody, iv8, that selects for naive human B cells expressing immunoglobulin light chains with 5-amino acid complementarity determining region 3s, a key feature of anti-CD4 binding site (CD4bs)-specific VRC01-class antibodies. In mice, iv8 induced target cells to expand and mature in the context of a polyclonal immune system and produced serologic responses targeting the CD4bs on Env. In summary, the results demonstrate that an anti-idiotypic antibody can specifically recognize and expand rare B cells that express VRC01-class antibodies against HIV-1.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / immunology*
  • Antibodies, Neutralizing / immunology*
  • B-Lymphocytes / immunology*
  • HIV Antibodies / immunology*
  • HIV Envelope Protein gp160 / genetics
  • HIV Envelope Protein gp160 / immunology*
  • HIV Infections / genetics
  • HIV Infections / immunology*
  • HIV-1 / immunology*
  • Humans
  • Mice
  • Mice, Transgenic


  • Antibodies, Anti-Idiotypic
  • Antibodies, Neutralizing
  • HIV Antibodies
  • HIV Envelope Protein gp160

Associated data

  • GENBANK/MK611925
  • GENBANK/MK611928
  • PDB/6MFT