Engineering antibody-like inhibitors to prevent and treat HIV-1 infection

Curr Opin HIV AIDS. 2017 May;12(3):294-301. doi: 10.1097/COH.0000000000000367.


Purpose of review: Here we discuss recently developed HIV-1 entry inhibitors that can target multiple epitopes on the HIV-1 envelope glycoprotein (Env), with an emphasis on eCD4-Ig. Some of these inhibitors are more potent and broader than any single antibody characterized to date. We also discuss the use of recombinant adeno-associated virus (rAAV) vectors as a platform for long-term expression of these inhibitors.

Recent findings: Much of the exterior of HIV-1 Env can be targeted by broadly neutralizing antibodies (bNAbs). Recent studies combine the variable regions or Fabs from different bNAbs, often with the receptor-mimetic components, to create broad, potent, and hard-to-escape inhibitors. rAAV vectors can express these inhibitors for years in vivo, highlighting their ability to prevent or treat HIV-1 infection.

Summary: By targeting multiple epitopes on Env, bispecific and antibody-like inhibitors can be broader and more potent than bNAbs. These inhibitors can provide long-term protection from, and perhaps suppression of, HIV-1 if they are administered by a delivery platform, like rAAV vectors, but only after rAAV limitations are addressed.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / immunology
  • Dependovirus / genetics
  • Dependovirus / metabolism
  • HIV Antibodies / administration & dosage*
  • HIV Antibodies / genetics*
  • HIV Antibodies / immunology
  • HIV Infections / drug therapy*
  • HIV Infections / genetics
  • HIV Infections / immunology
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • HIV-1 / immunology
  • HIV-1 / physiology
  • Humans
  • env Gene Products, Human Immunodeficiency Virus / antagonists & inhibitors
  • env Gene Products, Human Immunodeficiency Virus / genetics
  • env Gene Products, Human Immunodeficiency Virus / immunology


  • Anti-HIV Agents
  • HIV Antibodies
  • env Gene Products, Human Immunodeficiency Virus