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.