Inhibition of elastase enhances the adjuvanticity of alum and promotes anti–SARS-CoV-2 systemic and mucosal immunity
Eunsoo Kim, Zayed Attia, Rachel M. Woodfint, Cong Zeng, Sun Hee Kim, Haley Steiner, Rajni Kant Shukla, Namal P. M. Liyanage, Shristi Ghimire, Jiànróng Lǐ, Gourapura J. Renukaradhya, Abhay R. Satoskar, Amal O. Amer, Shan‐Lu Liu, Estelle Cormet‐Boyaka, Prosper N. Boyaka
Abstract
Significance We report that suppression of the serine protease elastase reshapes innate responses induced by injected vaccines containing alum adjuvant. This reprogramming improves the induction of protective antibodies in the bloodstream and stimulates innate signals, which support the development of antibody responses in mucosal tissues. Our findings identify elastase as the innate regulator that blunts the adjuvant activity of alum. They also demonstrate that vaccination via mucosal routes is not an absolute requirement for antibody responses in mucosal tissues and secretions. Supplementation of an alum-based vaccine containing SARS-CoV-2 spike protein subunit 1 as antigen increased anti–SARS-CoV-2 immunity in the blood and mucosal secretions in mice. Thus, this strategy could help in the development of future protein-based vaccines against SARS-CoV-2.