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Moon, James

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Moon

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James

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Moon, James
Author's Publications: search.filters.isAuthorOfPublication.4bacc294-584b-44e8-b4d6-e366921e7e9b

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    A Dual TLR Agonist Adjuvant Enhances the Immunogenicity and Protective Efficacy of the Tuberculosis Vaccine Antigen ID93
    (Public Library of Science, 2014) Orr, Mark T.; Beebe, Elyse A.; Hudson, Thomas E.; Moon, James; Fox, Christopher B.; Reed, Steven G.; Coler, Rhea N.
    With over eight million cases of tuberculosis each year there is a pressing need for the development of new vaccines against Mycobacterium tuberculosis. Subunit vaccines consisting of recombinant proteins are an attractive vaccine approach due to their inherent safety compared to attenuated live vaccines and the uniformity of manufacture. Addition of properly formulated TLR agonist-containing adjuvants to recombinant protein vaccines enhances the antigen-specific CD4+ T cell response characterized by IFN-γ and TNF, both of which are critical for the control of TB. We have developed a clinical stage vaccine candidate consisting of a recombinant fusion protein ID93 adjuvanted with the TLR4 agonist GLA-SE. Here we examine whether ID93+GLA-SE can be improved by the addition of a second TLR agonist. Addition of CpG containing DNA to ID93+GLA-SE enhanced the magnitude of the multi-functional TH1 response against ID93 characterized by co-production of IFN-γ, TNF, and IL-2. Addition of CpG also improved the protective efficacy of ID93+GLA-SE. Finally we demonstrate that this adjuvant synergy between GLA and CpG is independent of TRIF signaling, whereas TRIF is necessary for the adjuvant activity of GLA-SE in the absence of CpG.
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    Epitope mapping and kinetics of CD4 T cell immunity to pneumonia virus of mice in the C57BL/6 strain
    (Nature Publishing Group UK, 2017) Vandersarren, Lana; Bosteels, Cedric; Vanheerswynghels, Manon; Moon, James; Easton, Andrew J.; Van Isterdael, Gert; Janssens, Sophie; Lambrecht, Bart N.; van Helden, Mary J.
    Pneumonia virus of mice (PVM) infection has been widely used as a rodent model to study the closely related human respiratory syncytial virus (hRSV). While T cells are indispensable for viral clearance, they also contribute to immunopathology. To gain more insight into mechanistic details, novel tools are needed that allow to study virus-specific T cells in C57BL/6 mice as the majority of transgenic mice are only available on this background. While PVM-specific CD8 T cell epitopes were recently described, so far no PVM-specific CD4 T cell epitopes have been identified within the C57BL/6 strain. Therefore, we set out to map H2-IAb-restricted epitopes along the PVM proteome. By means of in silico prediction and subsequent functional validation, we were able to identify a MHCII-restricted CD4 T cell epitope, corresponding to amino acids 37–47 in the PVM matrix protein (M37–47). Using this newly identified MHCII-restricted M37–47 epitope and a previously described MHCI-restricted N339–347 epitope, we generated peptide-loaded MHCII and MHCI tetramers and characterized the dynamics of virus-specific CD4 and CD8 T cell responses in vivo. The findings of this study can provide a basis for detailed investigation of T cell-mediated immune responses to PVM in a variety of genetically modified C57BL/6 mice.
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    Changes in Depressive Symptoms and Incidence of First Stroke Among Middle-Aged and Older US Adults
    (Wiley Blackwell, 2015) Gilsanz, Paola; Walter, Stefan; Tchetgen, Eric; Patton, Kristen; Moon, James; Capistrant, Benjamin; Marden, Jessica Rachel; Kubzansky, Laura D; Kawachi, Ichiro; Glymour, Maria
    BACKGROUND: Although research has demonstrated that depressive symptoms predict stroke incidence, depressive symptoms are dynamic. It is unclear whether stroke risk persists if depressive symptoms remit. METHODS AND RESULTS: Health and Retirement Study participants (n=16 178, stroke free and noninstitutionalized at baseline) were interviewed biennially from 1998 to 2010. Stroke and depressive symptoms were assessed through self-report of doctors' diagnoses and a modified Center for Epidemiologic Studies - Depression scale (high was ≥3 symptoms), respectively. We examined whether depressive symptom patterns, characterized across 2 successive interviews (stable low/no, onset, remitted, or stable high depressive symptoms) predicted incident stroke (1192 events) during the subsequent 2 years. We used marginal structural Cox proportional hazards models adjusted for demographics, health behaviors, chronic conditions, and attrition. We also estimated effects stratified by age (≥65 years), race or ethnicity (non-Hispanic white, non-Hispanic black, Hispanic), and sex. Stroke hazard was elevated among participants with stable high (adjusted hazard ratio 2.14, 95% CI 1.69 to 2.71) or remitted (adjusted hazard ratio 1.66, 95% CI 1.22 to 2.26) depressive symptoms compared with participants with stable low/no depressive symptoms. Stable high depressive symptom predicted stroke among all subgroups. Remitted depressive symptoms predicted increased stroke hazard among women (adjusted hazard ratio 1.86, 95% CI 1.30 to 2.66) and non-Hispanic white participants (adjusted hazard ratio 1.66, 95% CI 1.18 to 2.33) and was marginally associated among Hispanics (adjusted hazard ratio 2.36, 95% CI 0.98 to 5.67). CONCLUSIONS:In this cohort, persistently high depressive symptoms were associated with increased stroke risk. Risk remained elevated even if depressive symptoms remitted over a 2-year period, suggesting cumulative etiologic mechanisms linking depression and stroke.