nasal immunization with a novel nanonemulsion adjuvant modifies th2-polarized immune responses
TRANSCRIPT
796 Late-Breaking Abstracts J ALLERGY CLIN IMMUNOL
MARCH 2008
CONCLUSIONS: The results of this study indicate that children livingin high areas of air pollution have higher baseline asthma severity. How-ever, once they are involved in a pediatric management program, the abil-ity to control their asthma is not affected by levels of air pollution.
LB20 Recombinant Peanut Allergens: Specific IgEs for Diagnosis
G. KANNY1, F. CODREANU1, S. JACQUENET2, C. ASTIER1, M. MORISSET1, D. MONERET-VAUTRIN1, C. Roland3, B. BIHAIN2; 1Nancy University, Nancy, FRANCE, 2Genclis, Nancy, FRANCE, 3Phadia, Uppsala, SWEDEN.RATIONALE: This study evaluated the diagnosis value of recombinantallergens to peanut.METHODS: Specific IgE to peanut (F13), recombinant allergens (rAra h1, rAra h 2, rAra h 3, rAra h 8) using ImmunoCAP system (Phadia, Sweden) were measured in 94 patients allergic to peanut (positive oralfood challenge), 39 controls allergic to grass and birch pollens and 50non-atopic.RESULTS: Patients allergic to peanut have sIgE to peanut (94), rAra h 2(93), rAra h 1 (74), rAra h 3 (62), rAra h 8 (45). Pollinic controls havesIgE to peanut (22), rAra h 2 (1), rAra h 1 (0), rAra h 3 (1), rAra h 8 (33).sIgE were negative in non atopic controls.The sensitivity and specificity were respectively 100% and 44% forpeanut, 99% and 97% for rArah 2.The reactogenic dose in oral challenge tests was 1876�2060 mg formono-sensitized to rAra h 2; 1567�1883 mg for co-sensitized to rAra h1 and rAra h 2 ; 620�329 mg for polysensitized to rAra h 1, rAra h 2 andrAra h 3.CONCLUSIONS: This study confirms the high sensitivity and specifici-ty of sIgE to rAra h 2. It is of particular interest for the diagnosis of peanutallergy in pollinic patients where the level of false positives for sIgE topeanut reached 56%. sIgE to rAra h 8 were detected in 85% of polliniccontrols, linked to the cross-reactivity with pollen allergens. The polysen-sitization is associated with a lower reactogenic threshold.
LB21 CD34+ Precursor Cells are Potent Effectors of AllergicInflammation
Z. Allakhverdi1, D. E. Smith2, M. R. Comeau2, G. J. Delespesse1;1CHUM Research Center, Montreal, QC, CANADA, 2InflammationResearch, Amgen, Seattle, WA.RATIONALE: Eosinophils, basophils and mast cells, the key effectors ofallergic diseases, are derived from common CD34+ myeloid precursorcells. The CD34+ cells are equipped with the appropriate chemokinereceptors and adhesion molecules allowing homing to inflammatory sites.We here provide evidence that in addition to being the precursors of clas-sical effectors, the CD34+ cells may behave as very potent effector cellsthat rapidly release high levels of proinflammatory cytokines/chemokinesin response to epithelial cell-derived cytokines, such as IL-33 and TSLP.METHODS: CD34+ progenitors were isolated from umbilical cord bloodand cultured in the presence of SCF/IL-3 with TSLP and/or IL-33 for 24hand the pellets and the supernatants were analyzed by real-time PCR orELISA.RESULTS: Freshly isolated CD34+ cells express TSLP and IL-33 recep-tor mRNA. Upon stimulation with TSLP and/or IL-33, the CD34+ cellsexpress IL-5, IL-13 and GM-CSF mRNAs and release high levels of sev-eral pro-inflammatory cytokines/chemokines such as IL-5, IL-6, IL-13,GM-CSF, CXCL8, CCL1, CCL17 and CCL22. The response is dose-dependent and specific, as it is blocked by neutralizing antibody to TSLPor by soluble ST2-Fc. Moreover, two color flow cytometry analysisreveals that all the cells producing IL-5 (or IL-13) are CD34+. Theresponse is rapid and is maximal after 18 h. In vivo significance of thesedata is supported by the finding of CD34+/IL-13+ cells in biopsies ofatopic dermatitis patients but not in controls.
CONCLUSIONS: Our data support the novel concept that CD34+ cellsare not only precursors but also potent effectors of allergic inflammation.
LB22 Nasal Immunization With A Novel Nanonemulsion Adjuvant Modifies Th2-polarized Immune Responses
J. R. Baker, Jr., K. W. Janczak, A. U. Bielinska; University of Michigan,Ann Arbor, MI.RATIONALE: Th2 immune responses are associated with allergy andwhile immunotherapeutic approaches have been used to shift immuneresponses from Th2 to Th1 phenotypes, they require long immunizationprotocols. We have developed a novel nasal vaccine system employing ananoemulsion (NE) that can simply be mixed with antigen and applied tothe nares to produce mucosal immunity and a systemic Th1-biasedimmune response. We hypothesized that a single administration of antigenin NE could re-direct an established Th2-type immune response.METHODS: To elicit a Th2 immune response, CD-1 mice were immu-nized intramuscularly with alum-adsorbed hepatitis B virus surface anti-gen (HBsAg). Analysis of serum IgG subclass and cytokine expressionconfirmed prevalence of IgG1 subclass antibodies and Th2 pattern ofcytokine expression. The mice were then given a single, intranasal immu-nization with HBsAg mixed with NE adjuvant.RESULTS: Titers of IgG2a and IgG2b subclass antibodies rose in miceafter NE nasal immunization and their splenic lymphocytes producedIFN-� in response to HBsAg. Antigen was found throughout the immunesystem within 24 hours after nasal administration, suggesting dendriticcell engagement. Of interest, there was no local inflammatory response inthe nares after NE immunized animals, and no local production of IL-12or other TH1 associated cytokines. NE also provided thermal stability forprotein antigens, avoiding the need for refrigeration of the vaccine afterformulation.CONCLUSIONS: These findings suggest potential importance for NEdelivery systems in the development of therapeutic vaccines to modifyTH2 immune responses.
LB23 Secondhand cigarette smoke may combine with commonrespiratory viruses to trigger exaggerated inflammationin CRS
D. L. Hamilos1, M. Yamin1, E. Holbrook2, N. Busaba2, S. Gray2, K. J. Powell1, R. Harold1, A. Sridhar1; 1Massachusetts General Hospital,Division of Rheumatology, Allergy & Immunology, Boston, MA, 2Mass-achusetts Eye and Ear Infirmary (MEEI), Boston, MA.BACKGROUND: Chronic rhinosinusitis (CRS) is characterized by per-sistent mucosal inflammation and frequent exacerbations. We hypothesizethat the innate epithelial response to common respiratory viral pathogensmay be abnormal leading to persistent inflammation in CRS. This mayinvolve Toll-like (TLR) receptors.METHODS: Nasal middle turbinate biopsies were obtained from 7healthy controls (HC) and 7 CRS patients. Primary nasal epithelial cells(PNEC) were cultured in LHC9 serum free medium. After reaching 80-90% confluence, PNEC were exposed to medium alone or cigarettesmoke extract (CSE) 5% (v/v) for 1 hour, washed, then stimulated for 24hours with double-stranded (ds)-RNA. For comparison, PNEC were stim-ulated with TNF- 100 ng/ml for 24 hours. After harvesting, gene expres-sion was quantified by RT-PCR relative to GAPDH.RESULTS: Baseline mRNA expression of TNF-, IL-1�, IL-6, IL-8,GRO-, �-defensin-2 (HBD2), RANTES, IFN�, IFN1 and IFN2/3revealed no differences between HC and CRS subjects. The combinationof CSE+dsRNA induced exaggerated RANTES (12115-fold versus 1500-fold, P = .03) and HBD-2 (1120-fold versus 12.5-fold, P = .05) productionin CRS subjects. By comparison, there were no differences in RANTESor HBD2 induction by CSE, dsRNA or TNF- alone. No other genes weredifferentially induced. No differences in TLR3 or IL-17 receptor mRNA