HIV-1 Therapeutic Inhibits Viral Entry

Soluble forms (sCD4) of human CD4, the HIV-1 primary receptor, are potent HIV-1 entry inhibitors. Both four-domain (D1-4) and two-domain (D1D2) sCD4 and their fusion proteins have been tested as candidate therapeutics in animal models and in human clinical trials and were well tolerated by patients with no significant clinical or immunologic toxicities and exhibited significant inhibitory activities. However, their activities were transient and the virus rapidly rebound. Additionally, sCD4 is known to interact with the class II major histocompatibility complex (MHCII) and, at low concentrations, it could enhance the HIV-1 infectivity. Researchers at the National Cancer Institute’s Nanobiology Program generated a novel polypeptide comprising a single human CD4 domain (mD1.22) that is highly soluble, stable and shows significantly increased neutralizing activity without measurable interaction with MHCII.

Competitive Advantages:

• Enhanced safety profile due to a lack of measurable interaction with MHCII
• Can be solubly expressed in E. coli with high yields leading to decreased production costs

Commercial Applications:

• As a prophylactic or an HIV therapeutic when conjugated with cytotoxic molecules
• Reagents for the rapid detection of HIV