22 research outputs found

    Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

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    Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

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    Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose

    Elevated Body Mass and Allergic Rhinits

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    AbstractBackground: Allergic rhinitis is a prevalent chronic respiratory problem that can impair quality of life, sleep and work. The increase in the prevalence of allergic rhinitis among the general population appears to have an association with weight. Obese individuals are more vulnerable to allergy. Since obesity appears to be linked with the occurrence of allergic rhinitis, it is hypothesized that obesity also has an influence on the severity levels of allergic rhinitis. This study was designed to investigate the patterns and severity of allergic rhinitis patients, determine the prevalence of obesity in patients with allergic rhinitis, examine theassociation between the severity of allergic rhinitis and body mass index, and develop recommendations for further research.Methods: This study involved a descriptive cross-sectional design. Forty five respondents aged 8 to 55 years recruited from an outpatient clinic in the Department of Immunology Fremantle Hospital from March to August 2007 completed a questionnaire, and had their height and weight measured by a trained researcher. Statistical analyses performed included chi-square, independent t-test, and logistic regression.Results: Increased BMI was associated with more severe conditions (up to six fold) of both nasal and non-nasal symptoms of Allergic Rhinitis.Conclusions: Weight control should be considered as a potential strategy to improve the health status of patients with Allergic Rhinitis, through the control of symptoms and the improvement of general health

    Rewiring of gene networks underlying mite allergen-induced CD4+Th-cell responses during immunotherapy

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    Background Multiple regulatory mechanisms have been identified employing conventional hypothesis-driven approaches as contributing to allergen-specific immunotherapy outcomes, but understanding of how these integrate to maintain immunological homeostasis is incomplete.Objective To explore the potential for unbiased systems-level gene co-expression network analysis to advance understanding of immunotherapy mechanisms.Methods We profiled genome-wide allergen-induced Th-cell responses prospectively during 24 months subcutaneous immunotherapy (SCIT) in 25 rhinitis, documenting changes in immunoinflammatory pathways and associated co-expression networks and their relationships to symptom scores out to 36 months.Results Prior to immunotherapy, mite-induced Th-cell response networks involved multiple discrete co-expression modules including those related to Th2-, type1 IFN-, inflammation- and FOXP3/IL2-associated signalling. A signature comprising 109 genes correlated with symptom scores, and these mapped to cytokine signalling/T-cell activation-associated pathways, with upstream drivers including hallmark Th1/Th2- and inflammation-associated genes. Reanalysis after 3.5 months SCIT updosing detected minimal changes to pathway/upstream regulator profiles despite 32.5% symptom reduction; however, network analysis revealed underlying merging of FOXP3/IL2-with inflammation-and Th2-associated modules. By 12 months SCIT, symptoms had reduced by 41% without further significant changes to pathway/upstream regulator or network profiles. Continuing SCIT to 24 months stabilized symptoms at 47% of baseline, accompanied by upregulation of the type1 IFN-associated network module and its merging into the Th2/FOXP3/IL2/inflammation module.Conclusions Subcutaneous immunotherapy stimulates progressive integration of mite-induced Th cell-associated Th2-, FOXP3/IL2-, inflammation- and finally type1 IFN-signalling subnetworks, forming a single highly integrated co-expression network module, maximizing potential for stable homeostatic control of allergen-induced Th2 responses via cross-regulation. Th2-antagonistic type1 IFN signalling may play a key role in stabilizing clinical effects of SCIT

    Patients accessing ambulatory care for HIV-infection: epidemiology and prevalence assessment

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    This study describes the demographics and treatment status of HIV-infected adults accessing ambulatory care in the Republic of Ireland and estimates diagnosed HIV prevalence rates. 3254 HIV-infected adults attended 1 of the 6 specialist HIV centres in the 12-month period 1 st July 2009 to 30 th June 2010. 2023/3254 (62%) were male, 1761/3133 (56%) Irish and 1048/3133 (34%) African. 1924/3098 (62%) resided in the Dublin area. The mean age was 39.8 years (SD 9.3); probable route of acquisition was available for 2898/3254 (89%); heterosexual acquisition accounted for 1442 (50%), MSM 777 (27%) and IDU 598 (21%). 2574/3202 (80%) were on highly active antiretroviral therapy (HAART).Of these 87% had HIV-RNA levels < 50cpm and 94% < 500cpm. The HIV diagnosed prevalence rate is estimated at 1.09/1000 nationally and at 2.25/1000 in the Dublin area for 15-59 year olds
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