Additionally, since the Tfr/Tfh ratio is skewed toward Tfr, targeting this cell type to block this highly suppressive function could increase Tfh cells and therefore, memory B cell and long-lived plasma cells response after infection or vaccination. It might also be beneficial to look at adjuvant therapy that will target DCs for improved pre-Tfh priming or antigen capture and presentation by FDCs in GC responses. Recently, we have reported that a novel adjuvant, adenosine deaminase (ADA-1), enhances the ability of Tfh to provide B cell help by creating a pro-Tfh microenvironment and, when administered as a molecular adjuvant in a HIV DNA vaccine, improves GC Tfh and B cell phenotype in the spleens and LN of vaccinated mice. This increase is also associated with increased env-binding antibody in the serum [8]. Better understanding of the interplay that controls GC responses in aging will undeniably have clinical applications and will be required to address the rising issue of the elderly and vaccination. We invite the scientific community to discuss the clinical benefit of this promising new research adjuvant and applications.