Inhibition of antigen-presentation attenuators to augment vaccines.

Antigen-presenting cells (APCs), such as dendritic cells (DCs), play a critical role in initiating and regulating immune responses. The mechanisms utilized by APCs to sense microbes and initiate immune responses have been well studied, however, little is known about the negative regulation of APCs. Recent studies demonstrate that suppressor of cytokine signaling 1 (SOCS1) functions as an antigen-presentation attenuator by controlling the tolerogenic state of DCs and the magnitude of antigen presentation. Inhibition of SOCS1 significantly enhances the ability of DC-based tumor vaccines to break self-tolerance and to induce effective antitumor immunity. Furthermore, inhibition of this antigen-presentation attenuator drastically boosts memory HIV-specific T- and B-cell responses induced by DC- and DNA-based HIV vaccines. This novel immunization strategy of 'inhibiting antigen-presentation attenuators' would be generally applicable to enhance both therapeutic and prophylactic vaccines against tumors and pathogens.