Risk of vaccine preventable diseases in UK migrants: A serosurvey and concordance analysis.

BACKGROUND: Vaccine preventable diseases (VPDs) such as measles and rubella cause significant morbidity and mortality globally every year. The World Health Organization (WHO), reported vaccine coverage for both measles and rubella to be 71 % in 2019, indicating an immunity gap. Migrants in the EU/EEA may be at high risk of VPDs due to under-immunisation and poor living conditions. However, there are limited data on VPD seroprotection rates amongst migrants living in the United Kingdom (UK). METHODS: We conducted an exploratory cross-sectional serosurvey amongst a sample of adult migrants living in Leicester, UK to: (a) determine seroprotection rates for measles, varicella zoster, and rubella in this group; (b) identify risk factors associated with seronegativity and, (c) understand if self-reported vaccine or diseases history is an effective measure of seroprotection. Participants gave a blood sample and completed a questionnaire asking basic demographic details and vaccine and disease history for the three VPDs. We summarised the data using median and interquartile range (IQR) for non-parametric continuous variables and count and percentage for categorical variables. We used logistic regression to establish predictors of seroprotection against these diseases. We examined the reliability of self-reported vaccination/disease history for prediction of seroprotection through a concordance analysis. RESULTS: 149 migrants were included in the analysis. Seroprotection rates were: varicella zoster 98 %, rubella 92.6 % and measles 89.3 %. Increasing age was associated with seroprotection (OR 1.07 95 % CI 1.01-1.13 for each year increase in age). Migrants from Africa and the Middle East (aOR 15.16 95 % CI 1.31 - 175.06) and South/East Asia and Pacific regions (aOR 15.43 95 %CI 2.38 - 100.00) are significantly more likely to be seroprotected against measles as compared to migrants from Europe and Central Asia. The proportions of migrants unsure about their vaccination and disease history combined were 53.0 % for measles; 57.7 % for rubella; 43.0 % for varicella. There was no agreement between self-reported vaccination/disease history and serostatus. CONCLUSION: Our findings suggest lower levels of seroprotection against measles in migrants living in Leicester, UK, with younger migrants and those from Europe and Central Asia more likely to lack seroprotection. A high proportion of surveyed migrants were unaware of their vaccination/disease history and self-reported vaccine/disease was a poor predictor of seroprotection against VPDs which is important for clinical decision-making regarding catch-up vaccination in this population. Our results, although derived from a small sample, suggest that there may be gaps in seroimmunity for certain VPDs in particular migrant populations. These findings should inform future qualitative studies investigating barriers to vaccine uptake in migrants and population-level seroprevalence studies aimed at determining individualised risk profiles based on demographic and migration factors

Group-2 innate lymphoid cell-dependent regulation of tissue neutrophil migration by alternatively activated macrophage-secreted Ear11.

Type-2 immunity is characterised by interleukin (IL)-4, IL-5 and IL-13, eosinophilia, mucus production, IgE, and alternatively activated macrophages (AAM). However, despite the lack of neutrophil chemoattractants such as CXCL1, neutrophils, a feature of type-1 immunity, are observed in type-2 responses. Consequently, alternative mechanisms must exist to ensure that neutrophils can contribute to type-2 immune reactions without escalation of deleterious inflammation. We now demonstrate that type-2 immune-associated neutrophil infiltration is regulated by the mouse RNase A homologue, eosinophil-associated ribonuclease 11 (Ear11), which is secreted by AAM downstream of IL-25-stimulated ILC2. Transgenic overexpression of Ear11 resulted in tissue neutrophilia, whereas Ear11-deficient mice have fewer resting tissue neutrophils, whilst other type-2 immune responses are not impaired. Notably, administration of recombinant mouse Ear11 increases neutrophil motility and recruitment. Thus, Ear11 helps maintain tissue neutrophils at homoeostasis and during type-2 reactions when chemokine-producing classically activated macrophages are infrequently elicited

1α,25(OH)2-3-Epi-Vitamin D3, a Natural Physiological Metabolite of Vitamin D3: Its Synthesis, Biological Activity and Crystal Structure with Its Receptor

Background: The 1 alpha,25-dihydroxy-3-epi-vitamin-D(3) (1 alpha,25(OH)(2)-3-epi-D(3)), a natural metabolite of the seco-steroid vitamin D(3), exerts its biological activity through binding to its cognate vitamin D nuclear receptor (VDR), a ligand dependent transcription regulator. In vivo action of 1 alpha,25(OH)(2)-3-epi-D(3) is tissue-specific and exhibits lowest calcemic effect compared to that induced by 1 alpha,25(OH)(2)D(3). To further unveil the structural mechanism and structure-activity relationships of 1 alpha,25(OH)(2)-3-epi-D3 and its receptor complex, we characterized some of its in vitro biological properties and solved its crystal structure complexed with human VDR ligand-binding domain (LBD). Methodology/Principal Findings: In the present study, we report the more effective synthesis with fewer steps that provides higher yield of the 3-epimer of the 1 alpha,25(OH)(2)D(3). We solved the crystal structure of its complex with the human VDR-LBD and found that this natural metabolite displays specific adaptation of the ligand-binding pocket, as the 3-epimer maintains the number of hydrogen bonds by an alternative water-mediated interaction to compensate the abolished interaction with Ser278. In addition, the biological activity of the 1 alpha,25(OH)(2)-3-epi-D(3) in primary human keratinocytes and biochemical properties are comparable to 1 alpha,25(OH)(2)D(3). Conclusions/Significance: The physiological role of this pathway as the specific biological action of the 3-epimer remains unclear. However, its high metabolic stability together with its significant biologic activity makes this natural metabolite an interesting ligand for clinical applications. Our new findings contribute to a better understanding at molecular level how natural metabolites of 1 alpha,25(OH)(2)D(3) lead to significant activity in biological systems and we conclude that the C3-epimerization pathway produces an active metabolite with similar biochemical and biological properties to those of the 1 alpha,25(OH)(2)D(3)

Valorisation of Biowastes for the Production of Green Materials Using Chemical Methods

With crude oil reserves dwindling, the hunt for a sustainable alternative feedstock for fuels and materials for our society continues to expand. The biorefinery concept has enjoyed both a surge in popularity and also vocal opposition to the idea of diverting food-grade land and crops for this purpose. The idea of using the inevitable wastes arising from biomass processing, particularly farming and food production, is, therefore, gaining more attention as the feedstock for the biorefinery. For the three main components of biomass—carbohydrates, lipids, and proteins—there are long-established processes for using some of these by-products. However, the recent advances in chemical technologies are expanding both the feedstocks available for processing and the products that be obtained. Herein, this review presents some of the more recent developments in processing these molecules for green materials, as well as case studies that bring these technologies and materials together into final products for applied usage

An immunological assay for identification of potential biofilm-associated antigens of Staphylococcus aureus

Attachment of bacterial pathogens to the niche tissue in the host is the first step in biofilm formation leading to colonization and establishment of infection in the host. While the most common method used for determining the potential role of a bacterial antigen in biofilm formation has been demonstration of loss of this property using specific knockout mutants, it is an expensive and a laborious procedure. This study describes an alternative immunological assay for identification of attachment antigens of Staphylococcus aureus, potentially important in the development of an effective vaccine against infections caused by this pathogen. The method is based upon the concept of inhibition of attachment of S. aureus to PEGs coated with virulence antigen-specific antibodies. Antibodies used for validation of this assay were specific for ClfA, FnBPA, SdrD, PNAG and a-toxin, accredited biofilm-associated antigens of S. aureus

Mammary Gland Pathology Subsequent to Acute Infection with Strong versus Weak Biofilm Forming Staphylococcus aureus Bovine Mastitis Isolates: A Pilot Study Using Non-Invasive Mouse Mastitis Model

BACKGROUND: Biofilm formation by Staphylococcus aureus is an important virulence attribute because of its potential to induce persistent antibiotic resistance, retard phagocytosis and either attenuate or promote inflammation, depending upon the disease syndrome, in vivo. This study was undertaken to evaluate the potential significance of strength of biofilm formation by clinical bovine mastitis-associated S. aureus in mammary tissue damage by using a mouse mastitis model. METHODS: Two S. aureus strains of the same capsular phenotype with different biofilm forming strengths were used to non-invasively infect mammary glands of lactating mice. Biofilm forming potential of these strains were determined by tissue culture plate method, ica typing and virulence gene profile per detection by PCR. Delivery of the infectious dose of S. aureus was directly through the teat lactiferous duct without invasive scraping of the teat surface. Both bacteriological and histological methods were used for analysis of mammary gland pathology of mice post-infection. RESULTS: Histopathological analysis of the infected mammary glands revealed that mice inoculated with the strong biofilm forming S. aureus strain produced marked acute mastitic lesions, showing profuse infiltration predominantly with neutrophils, with evidence of necrosis in the affected mammary glands. In contrast, the damage was significantly less severe in mammary glands of mice infected with the weak biofilm-forming S. aureus strain. Although both IL-1ß and TNF-a inflammatory biomarkers were produced in infected mice, level of TNF-a produced was significantly higher (p<0.05) in mice inoculated with strong biofilm forming S. aureus than the weak biofilm forming strain. CONCLUSION: This finding suggests an important role of TNF-a in mammary gland pathology post-infection with strong biofilm-forming S. aureus in the acute mouse mastitis model, and offers an opportunity for the development of novel strategies for reduction of mammary tissue damage, with or without use of antimicrobials and/or anti-inflammatory compounds for the treatment of bovine mastitis