Lysine β-Hydroxybutyrylation Improves Stability of COVID-19 Antibody

β-Hydroxybutyrate (3HB) is a small molecule produced as a ketone body in mammalian animals. It has been found that 3HB provides not only energy for a body, it also participates in cell signal transduction events as a signal molecule. This study focuses on investigation of 3HB immunomodulatory mechanisms. Proteomic analysis indicates a new post-translational modification of β-hydroxybutyrylation (Kbhb) on antibodies. Because of the low level of Kbhb antibodies and the associated difficulty in purifying them, simulated Kbhb antibody was produced using chemical modification in vitro. The chemically modified Kbhb antibody was shown to improve the stability of antibodies to protease and heat treatments. Furthermore, Kbhb of antibodies stabilizes the antibodies in plasma. As a remarkable example, COVID-19 neutralizing antibody B38 produced by 293T cells was Kbhb modified and stabilized in vivo, providing a strategy for the possibility of extending the protection effects of COVID-19 antibodies.