Mascola, John (NIAID)
Chuang, Gwo-Yu (NIAID)
Geng, Hui (NIAID)
Yang, Yongping (NIAID)
Cheng, Cheng (NIAID)
Boyington, Jeffrey (NIAID)
An effective human immunodeficiency virus type 1 (HIV-1) vaccine has long been sought to contend with the Acquired Immunodeficiency Syndrome (AIDS) pandemic.
One approach researchers have taken to elicit broadly neutralizing antibodies against HIV-1 is to stabilize the structurally flexible HIV-1 envelope (Env) trimer. Researchers stabilized the Env trimer in a conformation that displays predominantly broadly neutralizing epitopes and few non-neutralizing epitopes. Currently, BG505 DS-SOSIP is a leading vaccine candidate with the desired conformation and antigenicity.
Ideally, to be useful as a vaccine, such a conformationally fixed Env immunogen should have high thermostability and should remain in the desired antigenic state, even in the presence of CD4, a glycoprotein found on the surface of immune cells.
Researchers at the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID) undertook efforts to improve the properties of BG505 DS-SOSIP for use as a vaccine. The VRC researchers introduced three additional mutations to further stabilize BG505 DS-SOSIP in the vaccine-preferred prefusion-closed conformation and refer to the engineered BG505 DS-SOSIP as BG505 DS-SOSIP.3mut. Experiments showed that these modifications conferred improved thermostability that will allow easier transport and storage of BG505 DS-SOSIP.3mut compared to BG505 DS-SOSIP. In addition, BG505 DS-SOSIP.3mut has lower antigenicity toward non/weak neutralizing antibodies compared to BG505 DS-SOSIP, which suggests that it could potentially elicit higher neutralization titer by targeting only broadly neutralizing antibodies. With improved antigenicity and stability, this version may have utility as an HIV-1 immunogen or in other antigen-specific contexts, such as for use with B-cell probes.
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 for further development and evaluation under a research collaboration.
- Vaccine - to elicit potent neutralizing antibodies against the HIV-1 Env glycoprotein.
- Probes - to identify broad and potent HIV-1-neutralizing antibodies.
Compared to previous engineered Env trimer versions:
- 300- fold reduction in CD4-binding affinity.
- Reduced binding affinity to ineffective HIV-1 antibodies.
- Increase in melting temperature (10 degrees over BG505 SOSIP).