Application

Novel stabilized HIV-1 Clade C gp140 trimeric immunogen useful as a vaccine.

Key Benefits

• Vaccine for HIV-1 infections.
• Induces both neutralizing and V1V2 scaffold directed antibody responses.
• V1V2 scaffold directed antibodies bind to multiple strains of HIV-1 from different clades including Clades B and C.

Market Summary

HIV-1 is a virus having nine different subtypes, or clades. While most HIV clinical studies have been conducted in populations where subtype B predominate, subtype C accounts for a larger share (50%) of all people living with the disease. Traditional therapy for controlling HIV-1 infection in humans involves antiretroviral therapy (ART). While ART suppresses HIV-1 replication, it does not eliminate the viral reservoir or completely restore an infected individual's immune system. Major efforts to develop a prophylactic HIV-1 vaccine are under way.

Current attempts to produce viral vaccines focus on inducing neutralizing antibodies which inhibit viral entry into target cells. The recent RV144 efficacy trial demonstrated a key correlation between HIV-1 protection and non-neutralizing antibodies directed towards the variable loops 1-2 (V1V2 scaffold) of the HIV-1 gp120 envelope protein. In particular, antibodies directed toward a "hotspot" region within the V2 loop has been shown to correlate with a decreased risk of infection.

Technical Summary

Emory investigators adopted structure and sequence guided strategies to develop a novel Clade C immunogen which can induce antibodies with neutralizing and other anti-viral properties, along with generating broad V1V2 scaffold directed antibodies relative to the wildtype protein. These parameters are strong protective functions of an immunogen. The researchers developed stable C.1086 UFO (Uncleaved Full-Length Optimized) trimer with enhanced binding to broadly-cross reactive neutralizing antibodies, specifically PGT145. The stabilized imunogen induced (a) antibodies with tier-2 neutralizing and ADCVI activities, and (b) binding antibodies specific to trimeric Env with broad V1V2 scaffold reactivity that was a correlate in RV144 human trial.

Developmental Stage

The stabilized Clade C trimeric glycoprotein has been shown to induce both neutralizing and broad scaffold V1V2 specific binding activity in rabbits. The immunogenicity and protective ability of this vaccine will soon be tested in non-human primates.

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