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Francis J.N.,Immune Targeting Systems | Bunce C.J.,Immune Targeting Systems | Horlock C.,Immune Targeting Systems | Watson J.M.,Immune Targeting Systems | And 3 more authors.
Vaccine | Year: 2015

Background: FP-01.1 is a novel synthetic influenza A vaccine consisting of six fluorocarbon-modified 35-mer peptides that encapsulate multiple CD4+ and CD8+ T-cell epitopes and is designed to induce an immune response across a broad population. Methods: FP-01.1 was evaluated for safety and immunogenicity in a randomised, double-blind, placebo-controlled, dose-escalation, phase I clinical study in healthy adult volunteers (n= 49). IFNγ ELISpot assays and multicolour flow cytometry were used to characterise the immune response. Results: FP-01.1 was safe and well tolerated at all doses tested with a similar adverse event profile in actively vaccinated subjects compared with controls. Maximum immunogenicity was in the 150. μg/peptide dose group where a robust response (243 spots/million PBMC) was demonstrated in 75% subjects compared with 0% in placebo controls. All six peptides were immunogenic. FP-01.1 induced dual CD4+ and CD8+ T cell responses and vaccine-specific T cells cross-recognise divergent influenza strains. Conclusions: This first-in-human study showed that FP-01.1 has an acceptable safety and tolerability profile and generated robust anti-viral T cell responses in a high proportion of subjects tested. The results support the further clinical testing of FP-01.1 prior to clinical, proof-of-concept, live viral challenge studies. © 2014 The Authors. Source

Cahn A.,Glaxosmithkline | Boyce M.,Hammersmith Medicines Research Ltd | Mistry S.,Glaxosmithkline | Musani N.,Glaxosmithkline | And 4 more authors.
Clinical and Experimental Allergy | Year: 2015

Background: It is thought that asthmatics who smoke cigarettes respond less well to inhaled corticosteroid (ICS) therapy than asthmatics who do not smoke. Objective: To evaluate the effects of smoking on allergen-induced airway responses in asthmatics treated with ICS. Methods: Randomized, double-blind, crossover study evaluating twice daily fluticasone propionate (FP) 100 μg, FP 500 μg and placebo, for 7 days, on allergen-induced asthmatic responses in 18 non-smoking and 17 smoking atopic asthmatics (NCT01400906). At 1 h post-morning dose on Day 6, forced expiratory volume in 1 sec (FEV1) was measured up to 10 h post-challenge. Exhaled nitric oxide (eNO), induced sputum cell counts, and responsiveness to methacholine were assessed the following day. Results: The late asthmatic response (LAR) was suppressed by FP in smokers and non-smokers; with placebo, the LAR was also attenuated in smokers versus non-smokers (adjusted mean minimum change in FEV1 (L) over 4-10 h [95% CI] in non-smokers: placebo -1.01 [1.31, 0.70], FP 100 μg -0.38 [0.54, 0.22], FP 500 μg -0.35 [0.54-0.22]; and in smokers: placebo -0.63 [0.84, 0.43]; FP 100 μg -0.44 [0.65, 0.23]; FP 500 μg -0.46 [0.59-0.32]). The Early AR was suppressed by FP treatment in non-smokers, but was not impacted in smokers. The reduction in methacholine hyperresponsiveness after FP was greater in non-smokers (1.5- and twofold doubling dose difference from placebo after FP 100 μg and FP 500 μg) than smokers (1.0 and 1.3 difference, respectively). Allergen-induced increases in eNO and sputum eosinophils were lower in smokers than non-smokers and were suppressed in both groups by FP. Conclusion and Clinical Relevance: Allergen-induced LARs were of a similar amplitude in both smoking and non-smoking atopic asthmatics at the end of ICS treatment, but attenuation of the LAR in smokers was only partly associated with ICS treatment. The marked attenuation of the LAR observed in smokers in the absence of ICS treatment is a novel observation. © 2015 John Wiley & Sons Ltd. Source

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