High affinity mAb infusion can enhance maximum affinity maturation during HIV Env immunization

Area of Science:

• Immunology
• Vaccinology
• Molecular Biology

Background:

• Antigen-specific antibody infusion's effect on germinal center (GC) responses varies with antibody affinity.
• Understanding how antibody affinity influences B cell selection is crucial for vaccine development and immunotherapy.

Purpose of the Study:

• To investigate if escalating monoclonal antibody (mAb) affinity during immunization enhances B cell affinity maturation.
• To determine the impact of CD4 binding-site (CD4bs)-specific mAb infusion on B cell responses to HIV envelope gp120.

Main Methods:

• Mice were immunized with HIV envelope gp120.
• Mice received infusions of CD4bs-specific monoclonal antibodies (mAbs) with escalating affinity.
• Somatic hypermutation (SHM) and B cell affinity were analyzed using high-throughput sequencing of plasma cells.

Main Results:

• While most CD4bs-specific B cells showed reduced SHM and affinity, a subset exhibited increased SHM and affinity.
• Plasma cells from mAb-infused mice displayed elevated SHM.
• Phylogenetic analysis indicated accelerated differentiation in CD4bs-specific plasma cells.

Conclusions:

• High-affinity mAb infusion primarily suppresses most competing B cells.
• However, it can selectively increase and expedite affinity maturation in specific epitope-targeted B cell populations.
• This finding has implications for designing immunotherapies and vaccines.