Targeted Elimination of Immunodominant B Cells Drives the Germinal Center Reaction toward Subdominant Epitopes.

Rapidly evolving pathogens such as HIV or influenza can quickly mutate their antigenic profiles, reducing the efficacy of conventional vaccines. Despite this challenge, functionally required epitopes are highly conserved among heterologous viral strains and represent a key vulnerability that could be targeted during vaccine development. As the antigenicity of these conserved epitopes is frequently subdominant, there is a critical need for innovative vaccination strategies designed to target these neutralizing epitopes.

Fluorinated Adenosine A Receptor Antagonists Inspired by Preladenant as Potential Cancer Immunotherapeutics.

Antagonism of the adenosine A receptor on T cells blocks the hypoxia-adenosinergic pathway to promote tumor rejection. Using an immunoassay based on the Concanavalin A mouse model, a series of A antagonists were studied and identified preladenant as a potent lead compound for development. Molecular modeling was employed to assist drug design and subsequent synthesis of analogs and those of tozadenant, including fluorinated polyethylene glycol PEGylated derivatives.