Base-Covered HIV-1 Envelope Ectodomains and Their Use

Researchers at the Vaccine Research Center (“VRC”) of the National Institute of Allergy and Infectious Diseases (“NAID”) continue to pursue a safe and effective HIV-1 vaccine to combat the HIV-1/AIDS pandemic.

To this end, researchers have engineered the soluble HIV-1 ectodomain trimer so that it is stabilized in its prefusion conformation by artificial disulfides, helix-disrupting prolines, and other structure-based alterations. However, mice and non-human primates immunized with these engineered soluble HIV-1 trimers produced a significant (>90% in some cases) immune response to the exposed trimer base.

VRC researchers further modified the engineered prefusion soluble HIV-1 trimers by adding N-linked glycans to specific sites on the protein’s base to block this immunodominant surface. They found that these N-linked glycans did reduce production of non-neutralizing antibodies directed to the trimer base. These soluble, glycan-masked prefusion HIV-1 trimers are envisioned as being a part of a heterologous prime-boost vaccine regimen.

This technology is available for licensing for commercial development in accordance with 35 U.S.C. § 209 and 37 CFR Part 404, as well as further development and evaluation under a research collaboration.