Identification and characterization of a naturally occurring, efficiently cleaved, membrane-bound, clade A HIV-1 Env, suitable for immunogen design, with properties comparable to membrane-bound BG505

Virology. 2017 Oct:510:22-28. doi: 10.1016/j.virol.2017.07.001. Epub 2017 Jul 6.


Efficient cleavage of HIV-1 Env gp160 into its constituent subunits correlates with selective binding to neutralizing antibodies and are the closest mimetic of native, functional Envs. This was first demonstrated with the clade B Env, JRFL. The correlation between efficient cleavage and selective binding to neutralizing antibodies is the guiding principle for immunogen design for HIV vaccine. We have recently reported that Envs 4-2.J41 (clade C) and JRCSF (clade B) are also efficiently cleaved and show similar properties. However, an efficiently cleaved, membrane-bound clade A Env suitable for genetic vaccination has not been directly demonstrated. Here we report that BG505 and a new clade A Env, QB726.70M.ENV.C4 (or A5) are efficiently cleaved on cell membrane. A5 shows desirable antigenic properties comparable with BG505 on cell surface. A5SOSIP in supernatant displays majority of bNAb binding epitopes. Thus, both BG505 and A5 Envs can be used in DNA prime-protein boost vaccination studies.

Keywords: Broadly neutralizing antibodies; Clade A; Efficiently cleaved; Envelope; HIV-1.

Publication types

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

MeSH terms

  • Antibodies, Neutralizing / immunology*
  • Cell Membrane / metabolism
  • Epitopes / immunology
  • HIV Antibodies / immunology*
  • HIV Antigens / immunology*
  • HIV Antigens / metabolism*
  • Protein Binding
  • Proteolysis*
  • env Gene Products, Human Immunodeficiency Virus / immunology*
  • env Gene Products, Human Immunodeficiency Virus / metabolism*


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