Interrogating antiviral antibody responses with multiplexed, high-throughput serum assays

Area of Science:

• Immunology
• Virology
• Biotechnology

Background:

• The COVID-19 pandemic highlighted the need for rapid analysis of antibody responses to emerging viruses.
• Current methods struggle to simultaneously assess antibody recognition of multiple native-conformation antigens.
• High-throughput, multiplexed antibody profiling is crucial for understanding viral immunity.

Purpose of the Study:

• To develop a novel assay, Antibody Reactivity Characterization by Antibody-Dependent Enhancement (ARCADE), for high-throughput antibody profiling.
• To enable simultaneous assessment of antibody reactivity against multiple native-conformation viral antigens.
• To provide a comprehensive tool for analyzing antiviral antibody repertoires.

Main Methods:

• ARCADE utilizes an antigen-agnostic Fc receptor-expressing cell line.
• A library of genetically barcoded, antigen-displaying lentiviruses is employed.
• Infection rates of lentiviruses into cells correlate with antibody abundance and affinity in serum samples.

Main Results:

• ARCADE successfully characterized antibody responses using sera from COVID-19 convalescent and vaccinated individuals.
• The assay provided insights aligning with and extending findings from established immunoassays.
• ARCADE demonstrated that mRNA vaccines elicit broader and stronger antibody responses compared to adenovirus vector-based vaccines.

Conclusions:

• ARCADE is a powerful, multiplexed assay for profiling antibody reactivity against multiple viral antigens.
• The assay can comprehensively assess the impact of infection and vaccination on antiviral antibody repertoires.
• ARCADE offers valuable insights into vaccine efficacy and the dynamics of immune responses over time.