Person: Christou, Helen
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Christou
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Helen
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Christou, Helen
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Publication Adjuvant Effect of Bacille Calmette–Guérin on Hepatitis B Vaccine Immunogenicity in the Preterm and Term Newborn(Frontiers Media S.A., 2018) Scheid, Annette; Borriello, Francesco; Pietrasanta, Carlo; Christou, Helen; Diray-Arce, Joann; Pettengill, Matthew A.; Joshi, Sweta; Li, Ning; Bergelson, Ilana; Kollmann, Tobias; Dowling, David; Levy, OferImmunization is key to protecting term and preterm infants from a heightened risk of infection. However, preterm immunity is distinct from that of the term, limiting its ability to effectively respond to vaccines routinely given at birth, such as hepatitis B vaccine (HBV). As part of the Expanded Program on Immunization, HBV is often given together with the live-attenuated vaccine Bacille Calmette–Guérin (BCG), known to activate multiple pattern-recognition receptors. Of note, some clinical studies suggest BCG can enhance efficacy of other vaccines in term newborns. However, little is known about whether BCG can shape Th-polarizing cytokine responses to HBV nor the age-dependency of such effects, including whether they may extend to the preterm. To characterize the effects of BCG on HBV immunogenicity, we studied individual and combined administration of these vaccines to cord newborn and adult human whole blood and mononuclear cells in vitro and to neonatal and adult mice in vivo. Compared to either BCG or HBV alone, (BCG + HBV) synergistically enhanced in vitro whole blood production of IL-1β, while (BCG + HBV) also promoted production of several cytokines/chemokines in all age groups, age-specific enhancement included IL-12p70 in the preterm and GM-CSF in the preterm and term. In human mononuclear cells, (BCG + HBV) enhanced mRNA expression of several genes including CSF2, which contributed to clustering of genes by vaccine treatment via principle component analysis. To assess the impact of BCG on HBV immunization, mice of three different age groups were immunized subcutaneously with, BCG, HBV, (BCG + HBV) into the same site; or BCG and HBV injected into separate sites. Whether injected into a separate site or at the same site, co-administration of BCG with HBV significantly enhanced anti-HBV IgG titers in mice immunized on day of life-0 or -7, respectively, but not in adult mice. In summary, our data demonstrate that innate and adaptive vaccine responses of preterm and term newborns are immunologically distinct. Furthermore, BCG or “BCG-like” adjuvants should be further studied as a promising adjuvantation approach to enhance immunogenicity of vaccines to protect these vulnerable populations.Publication Hemopexin in severe inflammation and infection: mouse models and human diseases(BioMed Central, 2015) Lin, Tian; Maita, Dayana; Thundivalappil, Sujatha R; Riley, Frank E; Hambsch, Jasmin; Van Marter, Linda; Christou, Helen; Berra, Lorenzo; Fagan, Shawn; Christiani, David; Warren, H ShawIntroduction: Cell-free plasma hemoglobin is associated with poor outcome in patients with sepsis. Extracellular hemoglobin and secondarily released heme amplify inflammation in the presence of microbial TLR ligands and/or endogenous mediators. Hemopexin, a plasma protein that binds heme with extraordinary affinity, blocks these effects and has been proposed as a possible treatment approach to decrease inflammation in critically ill patients. Methods: We studied mouse models of endotoxemia, burn wound infections and peritonitis in order to assess if a repletion strategy for hemopexin might be reasonable. We also measured hemopexin in small numbers of three patient populations that might be logical groups for hemopexin therapy: patients with sepsis and ARDS, patients with severe burns, and premature infants. Results: Despite severe disease, mean plasma hemopexin levels were increased above baseline in each murine model. However, plasma hemopexin levels were decreased or markedly decreased in many patients in each of the three patient populations. Conclusions: Potentially different behavior of hemopexin in mice and humans may be important to consider when utilizing murine models to represent acute human inflammatory diseases in which heme plays a role. The findings raise the possibility that decreased hemopexin could result in insufficiently neutralized or cleared heme in some patients with ARDS, burns, or in premature infants who might be candidates to benefit from hemopexin administration. Electronic supplementary material The online version of this article (doi:10.1186/s13054-015-0885-x) contains supplementary material, which is available to authorized users.Publication Current Pharmacologic Approaches for Prevention and Treatment of Bronchopulmonary Dysplasia(Hindawi Publishing Corporation, 2012) Leeman, Kristen; Christou, HelenBronchopulmonary dysplasia (BPD) is a major complication of preterm birth and has serious adverse long-term health consequences. The etiology of BPD is complex, multifactorial, and incompletely understood. Contributing factors include ventilator-induced lung injury, exposure to toxic oxygen levels, and infection. Several preventive and therapeutic strategies have been developed with variable success. These include lung protective ventilator strategies and pharmacological and nutritional interventions. These strategies target different components and stages of the disease process and they are commonly used in combination. The purpose of this review is to discuss the evidence for current pharmacological interventions and identify future therapeutic modalities that appear promising in the prevention and management of BPD. Continued improved understanding of BPD pathogenesis leads to opportunities for newer preventive approaches. These will need to be evaluated in the setting of current clinical practice in order to assess their efficacy.