Supervised fine-tuning of pre-trained antibody language models improves antigen specificity prediction.

Antibodies play a crucial role in the adaptive immune response, with their specificity to antigens being a fundamental determinant of immune function. Accurate prediction of antibody-antigen specificity is vital for understanding immune responses, guiding vaccine design, and developing antibody-based therapeutics. In this study, we present a method of supervised fine-tuning for antibody language models, which improves on pre-trained antibody language model embeddings in binding specificity prediction to SARS-CoV-2 spike protein and influenza hemagglutinin. We perform supervised fine-tuning on four pre-trained antibody language models to predict specificity to these antigens and demonstrate that fine-tuned language model classifiers exhibit enhanced predictive accuracy compared to classifiers trained on pre-trained model embeddings. Additionally, we investigate the change of model attention activations after supervised fine-tuning to gain insights into the molecular basis of antigen recognition by antibodies. Furthermore, we apply the supervised fine-tuned models to BCR repertoire data related to influenza and SARS-CoV-2 vaccination, demonstrating their ability to capture changes in repertoire following vaccination. Overall, our study highlights the effect of supervised fine-tuning on pre-trained antibody language models as valuable tools to improve antigen specificity prediction.