Adenosine deaminase-1 enhances germinal center formation and functional antibody responses to HIV-1 Envelope DNA and protein vaccines

Gary, E.; O'Connor, Margaret; Chakhtoura, Marita; Tardif, Virginie; Kumova, Ogan K.; Malherbe, Delphine C.; Sutton, William F.; Haigwood, Nancy L.; Kutzler, Michele A.; Haddad, Elias K.

doi:10.1016/j.vaccine.2020.03.047

Cited by 12 publications

(24 citation statements)

References 37 publications

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“…(3) alter breadth or specificity of the response [97]; (4) and increase generation of memory responses [98].…”

Section: Adjuvants: Who Needs Them?mentioning

confidence: 99%

“…Secondly, adjuvants can qualitatively guide a tailored immune response to specific pathogens. For example, adjuvants have been used in preclinical and clinical studies to (1) skew the type of immune response (CD4 + vs. CD8 + , Th1 vs. Th2); (2) increase speed of initial response [ 97 ]; (3) alter breadth or specificity of the response [ 97 ]; (4) and increase generation of memory responses [ 98 ].…”

Section: Improving Aging Response To Vaccinesmentioning

confidence: 99%

“…Recently, adenosine deaminase-1 (ADA-1), an enzyme that is normally responsible for deaminating adenosine to produce inosine, has been shown to play a role in immune function by possibly creating an immunological synapse between CD26, an ADA-1 receptor on CD4 + T cells, and other ADA-1 receptors expressed on APCs. ADA-1 has also been reported to enhance the ability of pre-Tfh to provide B cell help as a plasmid in a HIV-1 DNA vaccine [ 98 ]. The use of molecular adjuvants in DNA or mRNA vaccines remains an important strategy to combat poor immunogenicity especially in the older adults.…”

Section: Improving Aging Response To Vaccinesmentioning

confidence: 99%

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The impact of immuno-aging on SARS-CoV-2 vaccine development

et al. 2021

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The SARS-CoV-2 pandemic has almost 56 million confirmed cases resulting in over 1.3 million deaths as of November 2020. This infection has proved more deadly to older adults (those >65 years of age) and those with immunocompromising conditions. The worldwide population aged 65 years and older is increasing, and the total number of aged individuals will outnumber those younger than 65 years by the year 2050. Aging is associated with a decline in immune function and chronic activation of inflammation that contributes to enhanced viral susceptibility and reduced responses to vaccination. Here we briefly review the pathogenicity of the virus, epidemiology and clinical response, and the underlying mechanisms of human aging in improving vaccination. We review current methods to improve vaccination in the older adults using novel vaccine platforms and adjuvant systems. We conclude by summarizing the existing clinical trials for a SARS-CoV-2 vaccine and discussing how to address the unique challenges for vaccine development presented with an aging immune system.

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“…(3) alter breadth or specificity of the response [97]; (4) and increase generation of memory responses [98].…”

Section: Adjuvants: Who Needs Them?mentioning

confidence: 99%

Section: Improving Aging Response To Vaccinesmentioning

confidence: 99%

Section: Improving Aging Response To Vaccinesmentioning

confidence: 99%

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The impact of immuno-aging on SARS-CoV-2 vaccine development

et al. 2021

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“…Total ADA, ADA1, and ADA2 have been explored as biomarkers (56-60, 94, 102, 103) and ADA1, as well as ADA receptor agonists/antagonists, are studied as possible vaccine adjuvants or disease-modifying drugs (20). In HIV infection, ADA1 concentration is decreased, addition of exogenous ADA1 enhances germinal center formation (102,104), and co-immunization with HIV-1 envelope protein and plasmid-encoded ADA1 enhanced humoral immunity (105). Characterizing baseline ADA concentrations in a target population may inform translational efforts to modulate ADAdeficient states via administration of recombinant ADA, HSCT, or gene therapy (21,106,107).…”

Section: Discussionmentioning

confidence: 99%

Plasma Adenosine Deaminase (ADA)-1 and -2 Demonstrate Robust Ontogeny Across the First Four Months of Human Life

et al. 2021

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BackgroundHuman adenosine deaminases (ADAs) modulate the immune response: ADA1 via metabolizing adenosine, a purine metabolite that inhibits pro-inflammatory and Th1 cytokine production, and the multi-functional ADA2, by enhancing T-cell proliferation and monocyte differentiation. Newborns are relatively deficient in ADA1 resulting in elevated plasma adenosine concentrations and a Th2/anti-inflammatory bias compared to adults. Despite the growing recognition of the role of ADAs in immune regulation, little is known about the ontogeny of ADA concentrations.MethodsIn a subgroup of the EPIC002-study, clinical data and plasma samples were collected from 540 Gambian infants at four time-points: day of birth; first week of life; one month of age; and four months of age. Concentrations of total extracellular ADA, ADA1, and ADA2 were measured by chromogenic assay and evaluated in relation to clinical data. Plasma cytokines/chemokine were measured across the first week of life and correlated to ADA concentrations.ResultsADA2 demonstrated a steady rise across the first months of life, while ADA1 concentration significantly decreased 0.79-fold across the first week then increased 1.4-fold by four months of life. Males demonstrated significantly higher concentrations of ADA2 (1.1-fold) than females at four months; newborns with early-term (37 to <39 weeks) and late-term (≥41 weeks) gestational age demonstrated significantly higher ADA1 at birth (1.1-fold), and those born to mothers with advanced maternal age (≥35 years) had lower plasma concentrations of ADA2 at one month (0.93-fold). Plasma ADA1 concentrations were positively correlated with plasma CXCL8 during the first week of life, while ADA2 concentrations correlated positively with TNFα, IFNγ and CXCL10, and negatively with IL-6 and CXCL8.ConclusionsThe ratio of plasma ADA2/ADA1 concentration increased during the first week of life, after which both ADA1 and ADA2 increased across the first four months of life suggesting a gradual development of Th1/Th2 balanced immunity. Furthermore, ADA1 and ADA2 were positively correlated with cytokines/chemokines during the first week of life. Overall, ADA isoforms demonstrate robust ontogeny in newborns and infants but further mechanistic studies are needed to clarify their roles in early life immune development and the correlations with sex, gestational age, and maternal age that were observed.

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“…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.…”

mentioning

confidence: 99%