9 research outputs found
Sublingual immunotherapy tablets as a disease-modifying add-on treatment option to pharmacotherapy for allergic rhinitis and asthma
<p>Allergic rhinitis (AR) with or without conjunctivitis (AR/C) is associated with a significant health and economic burden, and is often accompanied by asthma. Pharmacotherapies are the mainstay treatment options for AR and asthma, but guidelines also recommend allergy immunotherapy (AIT). Unlike pharmacotherapies, AIT has the ability to modify the underlying immunologic mechanisms of AR and asthma with the potential for long-term benefits after treatment is discontinued. Immunotherapy may also prevent progression of AR/C to asthma. Sublingual immunotherapy (SLIT)-tablets are a self-administered alternative to subcutaneous immunotherapy that provide the benefits of AIT without the cost and inconvenience of frequent office visits or the discomfort of injections. SLIT-tablets are also an option that can be utilized by primary care clinicians. Pharmacotherapies are generally effective in mild disease although a number of patients remain uncontrolled. SLIT-tablets have proven efficacy for AR in adults, children, and poly-sensitized allergic patients. Indirect comparisons indicate that SLIT-tablets have superior or comparable efficacy compared with traditional pharmacotherapies for seasonal AR, and superior efficacy for perennial AR. House dust mite (HDM) SLIT-tablets have also demonstrated clinically relevant benefits for asthma, with significant observed reductions in daily inhaled corticosteroid use, risk of asthma exacerbations, and asthma symptoms. SLIT-tablets are well tolerated, with minimal risk of systemic allergic reactions. The most common treatment-related adverse events are oral site reactions such as oral pruritus and throat irritation. Based on the favorable efficacy and safety profile, as well as the convenience of at-home oral administration and disease-modifying effects, SLIT-tablets should be considered as an alternative or add-on treatment to pharmacotherapy for AR/C, and as an add-on treatment for HDM allergic asthma.</p
Genetic variants in <i>TNF</i><b>α</b>, <i>TGFB1, PTGS1</i> and <i>PTGS2</i> genes are associated with diisocyanate-induced asthma
<div><p></p><p>Diisocyanates are the most common cause of occupational asthma, but risk factors are not well defined. A case-control study was conducted to investigate whether genetic variants in inflammatory response genes (<i>TNFα, IL1α, IL1β, IL1RN, IL10, TGFB1, ADAM33, ALOX-5, PTGS1, PTGS2</i> and <i>NAG-1/GDF15</i>) are associated with increased susceptibility to diisocyanate asthma (DA). These genes were selected based on their role in asthmatic inflammatory processes and previously reported associations with asthma phenotypes. The main study population consisted of 237 Caucasian French Canadians from among a larger sample of 280 diisocyanate-exposed workers in two groups: workers with specific inhalation challenge (SIC) confirmed DA (DA<sup>+</sup>, <i>n</i> = 95) and asymptomatic exposed workers (AW, <i>n</i> = 142). Genotyping was performed on genomic DNA, using a 5′ nuclease PCR assay. After adjusting for potentially confounding variables of age, smoking status and duration of exposure, the <i>PTGS1</i> rs5788 and <i>TGFB1</i> rs1800469 single nucleotide polymorphisms (SNP) showed a protective effect under a dominant model (OR = 0.38; 95% CI = 0.17, 0.89 and OR = 0.38; 95% CI = 0.18, 0.74, respectively) while the <i>TNFα</i> rs1800629 SNP was associated with an increased risk of DA (OR = 2.08; 95% CI = 1.03, 4.17). Additionally, the <i>PTGS2</i> rs20417 variant showed an association with increased risk of DA in a recessive genetic model (OR = 6.40; 95% CI = 1.06, 38.75). These results suggest that genetic variations in <i>TNFα, TGFB1, PTGS1</i> and <i>PTGS2</i> genes contribute to DA susceptibility.</p></div
DNA Priming for Seasonal Influenza Vaccine: A Phase 1b Double-Blind Randomized Clinical Trial
<div><p>Background</p><p>The efficacy of current influenza vaccines is limited in vulnerable populations. DNA vaccines can be produced rapidly, and may offer a potential strategy to improve vaccine immunogenicity, indicated by studies with H5 influenza DNA vaccine prime followed by inactivated vaccine boost.</p><p>Methods</p><p>Four sites enrolled healthy adults, randomized to receive 2011/12 seasonal influenza DNA vaccine prime (n=65) or phosphate buffered saline (PBS) (n=66) administered intramuscularly with Biojector. All subjects received the 2012/13 seasonal inactivated influenza vaccine, trivalent (IIV3) 36 weeks after the priming injection. Vaccine safety and tolerability was the primary objective and measurement of antibody response by hemagglutination inhibition (HAI) was the secondary objective.</p><p>Results</p><p>The DNA vaccine prime-IIV3 boost regimen was safe and well tolerated. Significant differences in HAI responses between the DNA vaccine prime and the PBS prime groups were not detected in this study.</p><p>Conclusion</p><p>While DNA priming significantly improved the response to a conventional monovalent H5 vaccine in a previous study, it was not effective in adults using seasonal influenza strains, possibly due to pre-existing immunity to the prime, unmatched prime and boost antigens, or the lengthy 36 week boost interval. Careful optimization of the DNA prime-IIV3 boost regimen as related to antigen matching, interval between vaccinations, and pre-existing immune responses to influenza is likely to be needed in further evaluations of this vaccine strategy. In particular, testing this concept in younger age groups with less prior exposure to seasonal influenza strains may be informative.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="http://clinicaltrials.gov/ct2/show/NCT01498718" target="_blank">NCT01498718</a></p></div
Influenza strains included in DNA vaccine prime and IIV3 boost.
<p>The trial was conducted at 4 clinical sites in the United States: Center for Vaccine Development, Saint Louis University, Saint Louis, Missouri; Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio; Hope Clinic of the Emory Vaccine Center, Atlanta, Georgia; and Baylor College of Medicine, Houston, Texas. The first subject was screened for recruitment on December 20, 2011, study vaccinations began on January 10, 2012 and study follow-up continued through April 17, 2013.</p><p>Influenza strains included in DNA vaccine prime and IIV3 boost.</p
VRC 701 Consort diagram of subject disposition.
<p>VRC 701 Consort diagram of subject disposition.</p
GMT 4 weeks Post-Boost for Study Groups by Baseline Immune Response: GMT (95% CI).
<p>GMT 4 weeks Post-Boost for Study Groups by Baseline Immune Response: GMT (95% CI).</p
Solicited Reactogencity within 7 Days of Injection.
<p>Note: Subjects are counted once at the maximum severity reported for each symptom.</p><p>Solicited Reactogencity within 7 Days of Injection.</p
Frequency of previous seasonal influenza vaccinations.
<p>*All subjects received 2011/2012 IIV3 at least 8 weeks prior to enrollment in the trial.</p><p>Frequency of previous seasonal influenza vaccinations.</p