Summary
Many options now exist for constructing oral vaccines which, in experimental systems, have shown themselves to be able to generate highly effective immunity against infectious diseases. Their ...suitability for implementation in clinical practice, however, for prevention of outbreaks, particularly in low‐ and middle‐income countries (LMIC), is not always guaranteed, because of factors such as cost, logistics and cultural and environmental conditions. This brief overview provides a summary of the various approaches which can be adopted, and evaluates them from a pharmaceutical point, taking into account potential regulatory issues, expense, manufacturing complexity, etc., all of which can determine whether a vaccine approach will be successful in the late stages of development. Attention is also drawn to problems arising from inadequate diet, which impacts upon success in stimulating effective immunity, and identifies the use of lipid‐based carriers as a way to counteract the problem of nutritional deficiencies in vaccination campaigns.
Routes of oral vaccine‐delivered antigens through the intestine, accessing different parts of the immune system of the body. (1) Via microcapillaries into the local and peripheral blood circulation; (2) via the lamina propria and intestinal lymphatics into the mesenteric lymph nodes; (3) direct uptake though M cells into the Peyer’s patches.
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Insects are the most diverse and abundant animals that share our world, and conservation initiatives are increasingly needed and being implemented globally, to safe guard the wealth of individual ...species. This book provides sufficient background information, illustrated by examples from many parts of the world, to enable more confident and efficient progress towards the conservation of these ecologically indispensable animals. Writing for graduate students, academic researchers and professionals, Tim New describes the major ingredients for insect species management and conservation, and how these may be integrated into effective practical management and recovery plans.
In addition to its search for extrasolar planets, the NASA Kepler mission provides exquisite data on stellar oscillations. We report the detections of oscillations in 500 solar-type stars in the ...Kepler field of view, an ensemble that is large enough to allow statistical studies of intrinsic stellar properties (such as mass, radius, and age) and to test theories of stellar evolution. We find that the distribution of observed masses of these stars shows intriguing differences to predictions from models of synthetic stellar populations in the Galaxy.
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•Induction of rapid immunity (d35); median serum IgG titres to F1 and V of >1800 and >2200 µg/ml respectively.•Induction of specific IgA in serum and faecal extracts.•Full protective efficacy against ...2 × 104 median lethal doses of Y. pestis (s.c.) at day 46, 14 days after single boost.•Oral dose effectively boosts systemic immunity and induced mucosal immunity.•VypVaxDuo fulfils rapid response criteria for a vaccine designed for emergency use authorisation.
Here, we report a dual-route vaccination approach for plague, able to induce a rapid response involving systemic and mucosal immunity, whilst also providing ease of use in those resource-poor settings most vulnerable to disease outbreaks. This novel vaccine (VypVaxDuo) comprises the recombinant F1 and V proteins in free association. VypVaxDuo has been designed for administration via a sub-cutaneous priming dose followed by a single oral booster dose and has been demonstrated to induce early onset immunity 14 days after the primary immunisation; full protective efficacy against live organism challenge was achieved in Balb/c mice exposed to 2 × 104 median lethal doses of Yersinia pestis Co92, by the sub-cutaneous route at 25 days after the oral booster immunisation. This dual-route vaccination effectively induced serum IgG and serum and faecal IgA, specific for F1 and V, which constitute two key virulence factors in Y. pestis, and is therefore suitable for further development to prevent bubonic plague and for evaluation in models of pneumonic plague. This is an essential requirement for control of disease outbreaks in areas of the world endemic for plague and is supported further by the observed exceptional stability of the primary vaccine formulation in vialled form under thermostressed conditions (40 °C for 29 weeks, and 40 °C with 75% relative humidity for 6 weeks), meaning no cold chain for storage or distribution is needed.
In clinical use, the injected priming dose would be administered on simple rehydration of the dry powder by means of a dual barrel syringe, with the subsequent single booster dose being provided in an enteric-coated capsule suitable for oral self-administration.
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To determine prevalence and co-existence of myositis specific autoantibodies (MSAs) and myositis associated autoantibodies (MAAs) and associated clinical characteristics in a large cohort of ...idiopathic inflammatory myopathy (IIM) patients.
Adult patients with confirmed IIM recruited to the EuroMyositis registry (n = 1637) from four centres were investigated for the presence of MSAs/MAAs by radiolabelled-immunoprecipitation, with confirmation of anti-MDA5 and anti-NXP2 by ELISA. Clinical associations for each autoantibody were calculated for 1483 patients with a single or no known autoantibody by global linear regression modelling.
MSAs/MAAs were found in 61.5% of patients, with 84.7% of autoantibody positive patients having a sole specificity, and only three cases (0.2%) having more than one MSA. The most frequently detected autoantibody was anti-Jo-1 (18.7%), with a further 21 specificities each found in 0.2–7.9% of patients. Autoantibodies to Mi-2, SAE, TIF1, NXP2, MDA5, PMScl and the non-Jo-1 tRNA-synthetases were strongly associated (p < 0.001) with cutaneous involvement. Anti-TIF1 and anti-Mi-2 positive patients had an increased risk of malignancy (OR 4.67 and 2.50 respectively), and anti-SRP patients had a greater likelihood of cardiac involvement (OR 4.15). Interstitial lung disease was strongly associated with the anti-tRNA synthetases, anti-MDA5, and anti-U1RNP/Sm. Overlap disease was strongly associated with anti-PMScl, anti-Ku, anti-U1RNP/Sm and anti-Ro60. Absence of MSA/MAA was negatively associated with extra-muscular manifestations.
Myositis autoantibodies are present in the majority of patients with IIM and identify distinct clinical subsets. Furthermore, MSAs are nearly always mutually exclusive endorsing their credentials as valuable disease biomarkers.
•Myositis specific autoantibodies very rarely coexist in the one individual allowing endotypes to be more precisely defined.•The association of anti-TIF1 and cancer-associated myositis is confirmed with a cut-off age of over 58 years.•In a large combined European myositis cohort associations of anti-SRP with carditis and anti-Mi-2 with cancer have emerged.•Myositis associated autoantibodies are strongly associated with having myositis in association with another connective tissue disease.
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•A novel dual route vaccination using the MERS-CoV RBD sub-unit has been developed.•Murine antisera induced to the RBD protein , were neutralising in vitro.•MERS-CoV susceptibility was induced in ...naïve mice with Ad5hDPP4.•Passive transfer of anti-RBD sera protected susceptible mice.•Protected mice had a significantly reduced viral titre (P = 0.02) in their lungs.
Murine antisera with neutralising activity for the coronavirus causative of Middle East respiratory syndrome (MERS) were induced by immunisation of Balb/c mice with the receptor binding domain (RBD) of the viral Spike protein. The murine antisera induced were fully-neutralising in vitro for two separate clinical strains of the MERS coronavirus (MERS-CoV). To test the neutralising capacity of these antisera in vivo, susceptibility to MERS-CoV was induced in naive recipient Balb/c mice by the administration of an adenovirus vector expressing the human DPP4 receptor (Ad5-hDPP4) for MERS-CoV, prior to the passive transfer of the RBD-specific murine antisera to the transduced mice. Subsequent challenge of the recipient transduced mice by the intra-nasal route with a clinical isolate of the MERS-CoV resulted in a significantly reduced viral load in their lungs, compared with transduced mice receiving a negative control antibody. The murine antisera used were derived from mice which had been primed sub-cutaneously with a recombinant fusion of RBD with a human IgG Fc tag (RBD-Fc), adsorbed to calcium phosphate microcrystals and then boosted by the oral route with the same fusion protein in reverse micelles. The data gained indicate that this dual-route vaccination with novel formulations of the RBD-Fc, induced systemic and mucosal anti-viral immunity with demonstrated in vitro and in vivo neutralisation capacity for clinical strains of MERS-CoV.
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A synopsis of the bark lice and book lice (Psocoptera) recorded from tropical Southeast Asia, including illustrated keys to all families and genera, together with distributional and biological notes, ...comprehensive references and a checklist of regional species.
Beetles, the most diverse group of insects, are often abundant in terrestrial and freshwater ecosystems. Many species are under threat from human changes to natural environments, and some are ...valuable tools in conservation, because they respond rapidly to changes that occur. Knowledge of these responses, of both abundance and composition of assemblages, enable use of some beetles to monitor environmental changes. Beetles impinge on humanity on many ways: as cultural objects, desirable collectables, major pests and competitors for resources need by people, as beneficial consumers of other pests, and by ensuring the continuity of vital ecological processes. This book is the first major global overview of the importance of conservation of beetles, and brings together much hitherto scattered information to demonstrate the needs for conservation, and how it may be approached. It is a source of value to students, research workers, conservation biologists and ecosystem managers as an introduction to the richness and importance of this predominant component of invertebrate life.
We present a list of ‘best possible’ estimates of low-degree p-mode frequencies from 8640 days of observations made by the Birmingham Solar-Oscillations Network (BiSON). This is the longest stretch ...of helioseismic data ever used for this purpose, giving exquisite precision in the estimated frequencies. Every effort has been made in the analysis to ensure that the frequency estimates are also accurate. In addition to presenting the raw best-fitting frequencies from our ‘peak-bagging’ analysis, we also provide tables of corrected frequencies pertinent to the quiet-Sun and an intermediate level of solar activity.
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We present the asteroseismic analysis of 1948 F-, G- and K-type main-sequence and subgiant stars observed by the National Aeronautics and Space Administration Kepler mission. We detect and ...characterize solar-like oscillations in 642 of these stars. This represents the largest cohort of main-sequence and subgiant solar-like oscillators observed to date. The photometric observations are analysed using the methods developed by nine independent research teams. The results are combined to validate the determined global asteroseismic parameters and calculate the relative precision by which the parameters can be obtained. We correlate the relative number of detected solar-like oscillators with stellar parameters from the Kepler Input Catalogue and find a deficiency for stars with effective temperatures in the range 5300 ≲T
eff≲ 5700 K and a drop-off in detected oscillations in stars approaching the red edge of the classical instability strip. We compare the power-law relationships between the frequency of peak power, νmax, the mean large frequency separation, Δν, and the maximum mode amplitude, A
max, and show that there are significant method-dependent differences in the results obtained. This illustrates the need for multiple complementary analysis methods to be used to assess the robustness and reproducibility of results derived from global asteroseismic parameters.
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