B cell epitope mapping: The journey to better vaccines and therapeutic antibodies

De Leon, Asha Joanne; Tjiam, M. Christian; Yu, Yu

doi:10.1016/j.bbagen.2024.130674

Biochimica et Biophysica Acta (BBA) - General Subjects

2024

DOI: 10.1016/j.bbagen.2024.130674

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B cell epitope mapping: The journey to better vaccines and therapeutic antibodies

Asha Joanne De Leon,

M. Christian Tjiam,

Yu Yu

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2024

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A rapid approach for linear epitope vaccine profiling reveals unexpected epitope tag immunogenicity

Browne-Cole,

Hanning,

Beijerling

et al. 2024

Preprint

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Antibody epitope profiling is essential for assessing the robustness of vaccine-induced immune responses, particularly while in development. Despite advancements in computational tools, high throughput experimental epitope validation remains an important step. Here, we describe a readily accessible method for rapid linear epitope profiling using phage-displayed oligo pools in combination with Nanopore deep sequencing. We applied this approach to TeeVax3, a Group A Streptococcus vaccine candidate, to investigate the antibody response generated in a pre-clinical rabbit model and assess antigen immunogenicity. Surprisingly, we found a strong bias in antibody binding response towards the N-terminal epitope tag used for purification. These tags are widely reported to have low immunogenicity and are frequently left uncleaved in pre-clinical studies. We further confirmed that the observed immune response against the epitope tag dominated even the conformational binding response and, using synthetic peptides, narrowed the epitope down to a set of 10 residues inclusive of the Histidine residues. Our findings highlight the importance of epitope-tag removal in pre-clinical studies and demonstrate the utility of rapid nanopore sequencing for early-stage vaccine evaluation.

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A rapid approach for linear epitope vaccine profiling reveals unexpected epitope tag immunogenicity

Browne-Cole,

Hanning,

Beijerling

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

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B cell epitope mapping: The journey to better vaccines and therapeutic antibodies

Cited by 1 publication

References 39 publications

A rapid approach for linear epitope vaccine profiling reveals unexpected epitope tag immunogenicity

A rapid approach for linear epitope vaccine profiling reveals unexpected epitope tag immunogenicity

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