Selective expansion of HIV-1 envelope glycoprotein-specific B cell subsets recognizing distinct structural elements...

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• The HIV-1 envelope glycoprotein (Env) employs immune evasion, limiting broadly neutralizing antibody targets.
• Current Env-based vaccines often induce antibodies with limited neutralizing breadth.
• Serological studies struggle to detail polyclonal antibody specificities and B cell dynamics post-immunization.

Purpose of the Study:

• To develop and apply a sensitive B cell ELISPOT system for enumerating Env-specific antibody-secreting cells (ASC).
• To analyze the evolution of B cell responses in mice immunized with engineered Env trimers.
• To investigate how homologous booster immunizations impact B cell subpopulations targeting specific Env determinants.

Main Methods:

• Development of a sensitive B cell ELISPOT system for enumerating antibody-secreting cells (ASC).
• Analysis of ASC from diverse anatomical compartments.
• Immunization of mice with engineered Env trimers in adjuvant, including homologous booster shots.

Main Results:

• Homologous booster immunizations significantly altered the proportion of ASC specific for defined Env structural elements.
• Selective expansion of ASC directed against variable regions of the Env spike was observed.
• The B cell ELISPOT system successfully enumerated ASC responses against different Env determinants.

Conclusions:

• The developed B cell ELISPOT system is a valuable tool for analyzing B cell responses to immunogens.
• B cell specificity and compartment analysis complement serological mapping for understanding immune responses.
• Understanding B cell evolution post-immunization is crucial for designing effective HIV vaccines.