Immunity & infection


Adenosine DeAminase (ADA) as an Adjuvant Molecule for Human HIV-1 Vaccine

Friday, June 16
1:25 PM - 1:40 PM

Follicular helper T cells (Tfh) play critical role in shaping, instructing, and initiating T-cell

dependent antibody responses. Understanding the underlying mechanisms that enhance their

function is therefore critical for vaccine development. Using a unique gene array analysis, we

have identified adenosine deaminase (ADA), as a novel key molecule that drives Tfh helper

program in proliferating Germinal Centers Tfh (GC Tfh) and circulatory Tfh (cTfh) cells following

their interactions with B cells. In fact, our gene array analysis showed that CD26 and ADA were

exclusively up-regulated within the less efficient cTfh1 (CD4+CD45RA-CXCR5+CXCR3+) and

cTfh2-17 (CD4+CD45RA-CXCR5+CXCR3+CCR6+/-) subsets, respectively. ADA enzymatic activity

is significantly higher, as well, in cTfh2-17 than in the less-efficient cTfh1 cells. Exogenous ADA

enhances the ability of Tfh cells to provide B cell help while inhibition of ADA activity by specific

inhibitors impeded Tfh function and blunted antibody response. Our results further

demonstrated that enhancement of Tfh function by ADA pathway could be due to increase in IL-

6 and decrease in IL-2 production in the co-culture, and maintenance of low extracellular

expression of CD26. Moreover, blocking IL-2 in cTfh2-17 co-culture from virally suppressed HIV

subjects (ST) showed a significant decrease of CD26 expression associated with a rescued

helper capacity. Finally, in vivo use of recombinant ADA as an adjuvant in a DNA based HIV

vaccine enhanced Tfh cells differentiation and enhanced anti-Env humoral response and

isotype class-switch.

Thus, ADA activity fine-tunes Tfh helper program and deciphering how ADA and CD26 regulate

the function of the cTfh subsets would benefit future vaccine adjuvant design.


Senior Post-Doc
Drexel Univerity College of Medicine


Send Email for Virginie TARDIF

Elias Haddad


Send Email for Elias Haddad


Adenosine DeAminase (ADA) as an Adjuvant Molecule for Human HIV-1 Vaccine

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