A Systematic Approach to HIV-1 Vaccine Immunogen Selection

Area of Science:

• Immunology
• Vaccinology
• Structural Biology

Background:

• Large-scale HIV vaccine efficacy trials incur significant financial and human resource losses.
• A systematic approach is needed to select promising HIV vaccine candidates for clinical development.

Purpose of the Study:

• To systematically compare the structure and antigenicity of three HIV envelope glycoprotein (Env) vaccine candidates: BG505 SOSIP.664, 1086.C gp140, and 1086.C gp120.
• To identify the most promising Env vaccine candidates for future HIV vaccine development.

Main Methods:

• Comparative analysis of the structure and antigenicity of three HIV Env vaccine candidates.
• Assessment of binding affinity to broadly neutralizing antibodies (bnAbs) and non-neutralizing antibodies (mAbs).

Main Results:

• BG505 SOSIP.664 trimer and 1086.C gp140 demonstrated superior performance over the 1086.C gp120 monomer.
• BG505 SOSIP.664 exhibited the strongest binding to potent bnAbs (PG9, PGT145, VRC01, PGT121).
• 1086.C gp140 showed strong binding to the protective non-neutralizing CH58 mAb, while 1086.C gp120 monomer showed the weakest antigenicity.

Conclusions:

• BG505 SOSIP.664 trimer and 1086.C gp140 are more promising HIV vaccine immunogens than the monomeric 1086.C gp120.
• A systematic preclinical evaluation of structure, antigenicity, immunogenicity, and efficacy is crucial for selecting optimal HIV vaccine candidates.
• This approach will optimize resource allocation and enhance the success rate of HIV vaccine development.