Vaccine elicitation of HIV broadly neutralizing antibodies from engineered B cells

Nat Commun. 2020 Nov 17;11(1):5850. doi: 10.1038/s41467-020-19650-8.

Abstract

HIV broadly neutralizing antibodies (bnAbs) can suppress viremia and protect against HIV infection. However, their elicitation is made difficult by low frequencies of appropriate precursor B cell receptors and the complex maturation pathways required to generate bnAbs from these precursors. Antibody genes can be engineered into B cells for expression as both a functional antigen receptor on cell surfaces and as secreted antibody. Here, we show that HIV bnAb-engineered primary mouse B cells can be adoptively transferred and vaccinated in immunocompetent mice resulting in the expansion of durable bnAb memory and long-lived plasma cells. Somatic hypermutation after immunization indicates that engineered cells have the capacity to respond to an evolving pathogen. These results encourage further exploration of engineered B cell vaccines as a strategy for durable elicitation of HIV bnAbs to protect against infection and as a contributor to a functional HIV cure.

Publication types

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

MeSH terms

  • AIDS Vaccines / immunology*
  • Animals
  • Antibodies, Monoclonal / blood
  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / immunology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / physiology
  • B-Lymphocytes / transplantation
  • Broadly Neutralizing Antibodies / blood
  • Broadly Neutralizing Antibodies / genetics
  • Broadly Neutralizing Antibodies / immunology*
  • Female
  • Genetic Engineering / methods
  • HEK293 Cells
  • HIV Antibodies / blood
  • HIV Antibodies / genetics
  • HIV Antibodies / immunology
  • HIV Infections
  • Humans
  • Immunization
  • Immunologic Memory / genetics
  • Lymphocyte Activation
  • Mice, Inbred C57BL
  • Somatic Hypermutation, Immunoglobulin

Substances

  • AIDS Vaccines
  • Antibodies, Monoclonal
  • Broadly Neutralizing Antibodies
  • HIV Antibodies
  • VRC01 monoclonal antibody