A Transgenic Mouse With a Humanized B-Cell Repertoire Mounts an Antibody Response to Influenza Infection and Vaccination
By
Valarmathy Murugaiah
Simon J Watson
Robert F Cunliffe
Nigel J Temperton
Stevo T Reece
Paul Kellam
John S Tregoning
September 24, 2024
Clinical Scorecard: A Humanized B-Cell Repertoire in Transgenic Mice Generates Antibody Responses to Influenza Infection and Vaccination
At a Glance
Category Detail
Condition Influenza virus infection and vaccination Key Mechanisms Humanized B-cell repertoire in transgenic mice (Kymouse) enables human-like antibody evolution and response to influenza infection and vaccination Target Population Research models using transgenic mice with human immunoglobulin loci to study influenza immunity Care Setting Preclinical research and vaccine development laboratories
Key Highlights
Kymouse transgenic mice possess a complete human immunoglobulin variable gene repertoire enabling human-like antibody responses. Kymouse are susceptible to infection by multiple influenza strains (H1N1, H3N2, B/Yamagata) and generate robust binding and neutralizing antibodies. This model provides a tool to study original antigenic sin and antibody evolution relevant to universal influenza vaccine development. Guideline-Based Recommendations
Diagnosis
Use of transgenic mice with humanized B-cell repertoires can model human antibody responses to influenza infection and vaccination. Management
Employ Kymouse models to evaluate immune responses to different influenza virus strains and vaccine candidates. Utilize prime-boost regimens in Kymouse to study subtype-specific antibody responses. Monitoring & Follow-up
Measure binding and neutralizing antibody titers post-infection or vaccination in Kymouse to assess immune response quality. Risks
Consider limitations of murine constant regions in antibodies despite human variable regions when interpreting results. Recognize that animal models may not fully replicate human immune history and complexity. Patient & Prescribing Data
Not applicable; study involves transgenic mouse models for preclinical research.
Kymouse models enable controlled study of influenza exposure history and antibody repertoire shaping, informing universal vaccine design.
Clinical Best Practices
Use transgenic mice with human immunoglobulin loci to overcome species differences in B-cell repertoires when studying influenza immunity. Incorporate multiple influenza virus subtypes in infection and vaccination studies to evaluate breadth of antibody responses. Apply prime-boost vaccination strategies in preclinical models to mimic human exposure and study original antigenic sin effects. References
