Immunity & infection

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Adenosine Deaminase (ada) as an Adjuvant Molecule for Human hiv-1 Vaccine

Friday, June 16
6:15 PM - 7:30 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.

Virginie JULIE. TARDIF

Senior Post-Doc
Drexel Univerity College of Medicine

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    Elias Haddad

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