Is the vaccination-induced B cell receptor repertoire predictable?

Area of Science:

• Immunology
• Vaccinology
• Bioinformatics

Background:

• Vaccines induce memory B cells with specific B cell receptors (BCRs) for rapid antigen response.
• Post-vaccination, B cell expansion leads to measurable vaccine-specific BCR clonotypes.

Purpose of the Study:

• To assess the predictability of specific BCR clonotypes induced by vaccination in individuals.
• To compare different methods for predicting vaccine-induced BCR clonotypes.

Main Methods:

• Sequenced BCR heavy chain repertoires from 19 individuals before and after Tdap booster vaccination.
• Evaluated two prediction modalities: monoclonal antibody database look-up and a leave-one-out cross-validation approach using cohort data.

Main Results:

• A leave-one-out approach, predicting clonotypes using data from other individuals, significantly outperformed direct sequence look-up methods.
• BCR clonotype expansion patterns are learnable across subjects, indicating potential for cross-individual prediction.

Conclusions:

• Vaccine-induced BCR clonotype expansion is predictable across individuals, supporting the value of systematic BCR specificity data collection.
• Highlights limitations of general prediction methods due to small datasets of known BCR specificities and provides a framework for repertoire comparison.