Humanized B-Cell Repertoire in Transgenic Mice Enables Influenza Antibody Responses

Overview

The study demonstrates that Kymouse transgenic mice, which possess a humanized B-cell repertoire, are susceptible to influenza infection and generate robust binding and neutralizing antibody responses to multiple influenza strains. This model provides a valuable tool for studying human-like antibody evolution and vaccine responses against influenza.

Background

Influenza remains a major cause of morbidity and mortality worldwide, with vaccination as the primary preventive strategy. However, vaccine efficacy varies annually due to viral antigenic variability and mismatches between vaccine and circulating strains. The concept of original antigenic sin (OAS) complicates vaccine design, as prior influenza exposure shapes subsequent antibody responses. Animal models often lack a human-like B-cell repertoire, limiting their translational relevance. The Kymouse transgenic model, containing human immunoglobulin loci, offers a platform to study human antibody responses to influenza infection and vaccination.

Data Highlights

The Kymouse was infected with H1N1, H3N2, and B/Yamagata influenza viruses, demonstrating susceptibility to disease and induction of robust binding and neutralizing antibody responses across all three strains. The study confirmed the generation of subtype-specific antibodies following prime-boost regimens, highlighting the model's capacity to mimic human antibody evolution.

Key Findings

• Kymouse transgenic mice possess a complete human immunoglobulin variable gene repertoire enabling human-like antibody responses.
• The mice are susceptible to infection by multiple influenza virus subtypes: H1N1, H3N2, and B/Yamagata.
• Following infection or vaccination, Kymice generate robust binding and neutralizing antibodies specific to each influenza strain.
• The model supports studies of original antigenic sin and antigenic imprinting in the context of influenza immunity.
• Kymice provide a controlled system to investigate the evolution of human antibody responses to influenza infection and vaccination.

Clinical Implications

The Kymouse model offers a novel preclinical platform to study human B-cell responses to influenza, facilitating the evaluation of vaccine candidates and understanding of immune imprinting phenomena. This can accelerate the development of universal influenza vaccines by enabling detailed interrogation of antibody evolution and cross-reactivity in a humanized immune context.

Conclusion

Kymouse transgenic mice with a humanized B-cell repertoire effectively model human antibody responses to influenza infection and vaccination, providing a valuable tool for advancing universal influenza vaccine research.

References

1. Imperial College London/2023 -- A Humanized B-Cell Repertoire in Transgenic Mice Generates Antibody Responses to Influenza Infection and Vaccination