2,165 research outputs found
Evaluation of a novel fully automated and ELISA-based assays for detecting anti- SARS- CoV-2 neutralizing antibodies
Evaluation of commercially available fully automated and ELISA-based assays for detecting anti-SARS-CoV-2 neutralizing antibodies
Rapid and accurate measurement of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)-specific neutralizing antibodies (nAbs) is paramount for monitoring immunity in infected and vaccinated subjects. The current gold standard relies on pseudovirus neutralization tests which require sophisticated skills and facilities. Alternatively, recent competitive immunoassays measuring anti-SARS-CoV-2 nAbs are proposed as a quick and commercially available surrogate virus neutralization test (sVNT). Here, we report the performance evaluation of three sVNTs, including two ELISA-based assays and an automated bead-based immunoassay for detecting nAbs against SARS-CoV-2. The performance of three sVNTs, including GenScript cPass, Dynamiker, and Mindray NTAb was assessed in samples collected from SARS-CoV-2 infected patients (n = 160), COVID-19 vaccinated individuals (n = 163), and pre-pandemic controls (n = 70). Samples were collected from infected patients and vaccinated individuals 2–24 weeks after symptoms onset or second dose administration. Correlation analysis with pseudovirus neutralization test (pVNT) and immunoassays detecting anti-SARS-CoV-2 binding antibodies was performed. Receiver operating characteristic (ROC) curve analysis was generated to assess the optimal threshold for detecting nAbs by each assay. All three sVNTs showed an excellent performance in terms of specificity (100%) and sensitivity (100%, 97.0%, and 97.1% for GenScript, Dynamiker, and Mindray, respectively) in samples collected from vaccinated subjects. GenScript demonstrated the strongest correlation with pVNT (r = 0.743, R(2) = 0.552), followed by Mindray (r = 0.718, R(2) = 0.515) and Dynamiker (r = 0.608, R(2) = 0.369). Correlation with anti-SARS-CoV-2 binding antibodies was variable, but the strongest correlations were observed between anti-RBD IgG antibodies and Mindray (r = 0.952, R(2) = 0.907). ROC curve analyses demonstrated excellent performance for all three sVNT assays in both groups, with an AUC ranging between 0.99 and 1.0 (p < 0.0001). Also, it was shown that the manufacturer's recommended cutoff values could be modified based on the tested cohort without significantly affecting the sVNT performance. The sVNT provides a rapid, low-cost, and scalable alternative to conventional neutralization assays for measuring and expanding nAbs testing across various research and clinical settings. Also, it could aid in evaluating actual protective immunity at the population level and assessing vaccine effectiveness to lay a foundation for boosters' requirements
Are HIV epidemics among men who have sex with men emerging in the Middle East and North Africa?: a systematic review and data synthesis.
BACKGROUND: Men who have sex with men (MSM) bear a disproportionately higher burden of HIV infection than the general population. MSM in the Middle East and North Africa (MENA) are a largely hidden population because of a prevailing stigma towards this type of sexual behavior, thereby limiting the ability to assess infection transmission patterns among them. It is widely perceived that data are virtually nonexistent on MSM and HIV in this region. The objective of this review was to delineate, for the first time, the evidence on the epidemiology of HIV among MSM in MENA. METHODS AND FINDINGS: This was a systematic review of all biological, behavioral, and other related data on HIV and MSM in MENA. Sources of data included PubMed (Medline), international organizations' reports and databases, country-level reports and databases including governmental and nongovernmental organization publications, and various other institutional documents. This review showed that onsiderable data are available on MSM and HIV in MENA. While HIV prevalence continues at low levels among different MSM groups, HIV epidemics appear to be emerging in at least few countries, with a prevalence reaching up to 28% among certain MSM groups. By 2008, the contribution of MSM transmission to the total HIV notified cases increased and exceeded 25% in several countries. The high levels of risk behavior (4-14 partners on average in the last six months among different MSM populations) and of biomarkers of risks (such as herpes simplex virus type 2 at 3%-54%), the overall low rate of consistent condom use (generally below 25%), the relative frequency of male sex work (20%-76%), and the substantial overlap with heterosexual risk behavior and injecting drug use suggest potential for further spread. CONCLUSIONS: This systematic review and data synthesis indicate that HIV epidemics appear to be emerging among MSM in at least a few MENA countries and could already be in a concentrated state among several MSM groups. There is an urgent need to expand HIV surveillance and access to HIV testing, prevention, and treatment services in a rapidly narrowing window of opportunity to prevent the worst of HIV transmission among MSM in the Middle East and North Africa. Please see later in the article for the Editors' Summary
Characterizing HIV epidemiology in stable couples in Cambodia, the Dominican Republic, Haiti, and India.
Using a set of statistical methods and HIV mathematical models applied on nationally representative Demographic and Health Survey data, we characterized HIV serodiscordancy patterns and HIV transmission dynamics in stable couples (SCs) in four countries: Cambodia, the Dominican Republic, Haiti, and India. The majority of SCs affected by HIV were serodiscordant, and about a third of HIV-infected persons had uninfected partners. Overall, nearly two-thirds of HIV infections occurred in individuals in SCs, but only about half of these infections were due to transmissions within serodiscordant couples. The majority of HIV incidence in the population occurred through extra-partner encounters in SCs. There is similarity in HIV epidemiology in SCs between these countries and countries in sub-Saharan Africa, despite the difference in scale of epidemics. It appears that HIV epidemiology in SCs may share similar patterns globally, possibly because it is a natural 'spillover' effect of HIV dynamics in high-risk populations
Comparable antibody levels in heterologous and homologous mRNA COVID-19 vaccination, with superior neutralizing and IgA antibody responses in mRNA homologous boosting
BackgroundPriming with two doses of AZD1222 (Oxford-AstraZeneca; ChAd) followed by a third mRNA vaccine boosting is considered in several countries, yet comparisons between heterologous and homologous booster efficacy remain unexplored. AimTo evaluate and contrast the immunogenicity of homologous and heterologous boosting regimens. MethodThe study examined antibody responses in 1113 subjects, comprising 895 vaccine-naïve individuals across different vaccination strategies (partial, primary series, heterologous booster, homologous booster) and 218 unvaccinated, naturally infected individuals. Assessments included neutralizing total antibodies (NTAbs), total antibodies (TAbs), anti-S-RBD IgG, and anti-S1 IgA levels. ResultsThe study found mRNA vaccines to exhibit superior immunogenicity in primary series vaccination compared to ChAd, with mRNA-1273 significantly enhancing NTAbs, TAbs, anti-S-RBD IgG, and anti-S1 IgA levels (p < 0.001). Both booster types improved antibody levels beyond primary outcomes, with no significant difference in TAbs and anti-S-RBD IgG levels between regimens. However, homologous mRNA boosters significantly outperformed heterologous boosters in enhancing NTAbs and anti-S1 IgA levels, with the BNT/BNT/BNT regimen yielding particularly higher enhancements (p < 0.05). ConclusionThe study concludes that although TAbs and anti-S-RBD IgG antibody levels are similar for both regimens, homologous mRNA boosting outperform heterologous regimen by enhancing anti-S1 IgA and neutralizing antibody levels.GKN would like to acknowledge the funding from WHO grant number COVID-19-22-43 and Qatar University grant No. QUCG-BRC-23/24-170. This work was also made possible by grants number UREP29-026-3-004 and UREP28-173-3-057 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the authors
Inequalities in the incidence of cervical cancer in South East England 2001-2005: an investigation of population risk factors.
BACKGROUND: The incidence of cervical cancer varies dramatically, both globally and within individual countries. The age-standardised incidence of cervical cancer was compared across primary care trusts (PCTs) in South East England, taking into account the prevalence of known behavioural risk factors, screening coverage and the deprivation of the area. METHODS: Data on 2,231 cases diagnosed between 2001 and 2005 were extracted from the Thames Cancer Registry, and data on risk factors and screening coverage were collated from publicly available sources. Age-standardised incidence rates were calculated for each PCT using cases of squamous cell carcinoma in the screening age group (25-64 years). RESULTS: The age-standardised incidence rate for cervical cancer in South East England was 6.7 per 100,000 population (European standard) but varied 3.1 fold between individual PCTs. Correlations between the age-standardised incidence rate and smoking prevalence, teenage conception rates, and deprivation were highly significant at the PCT level (p < 0.001). However, screening coverage was not associated with the incidence of cervical cancer at the PCT level. Poisson regression indicated that these variables were all highly correlated and could not determine the level of independent contribution at a population level. CONCLUSION: There is excess disease burden within South East England. Significant public health gains can be made by reducing exposure to known risk factors at a population level
SARS-CoV-2 infection triggers more potent antibody-dependent cellular cytotoxicity (ADCC) responses than mRNA-, vector-, and inactivated virus-based COVID-19 vaccines
Neutralizing antibodies (NAbs) are elicited after infection and vaccination and have been well studied. However, their antibody-dependent cellular cytotoxicity (ADCC) functionality is still poorly characterized. Here, we investigated ADCC activity in convalescent sera from infected patients with wild-type (WT) severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or omicron variant compared with three coronavirus disease 2019 (COVID-19) vaccine platforms and postvaccination breakthrough infection (BTI). We analyzed ADCC activity targeting SARS-CoV-2 spike (S) and nucleocapsid (N) proteins in convalescent sera following WT SARS-CoV-2-infection (n = 91), including symptomatic and asymptomatic infections, omicron-infection (n = 8), COVID-19 vaccination with messenger RNA- (mRNA)- (BNT162b2 or mRNA-1273, n = 77), adenovirus vector- (n = 41), and inactivated virus- (n = 46) based vaccines, as well as post-mRNA vaccination BTI caused by omicron (n = 28). Correlations between ADCC, binding, and NAb titers were reported. ADCC was elicited within the first month postinfection and -vaccination and remained detectable for ≥3 months. WT-infected symptomatic patients had higher S-specific ADCC levels than asymptomatic and vaccinated individuals. Also, no difference in N-specific ADCC activity was seen between symptomatic and asymptomatic patients, but the levels were higher than the inactivated vaccine. Notably, omicron infection showed reduced overall ADCC activity compared to WT SARS-CoV-2 infection. Although post-mRNA vaccination BTI elicited high levels of binding and NAbs, ADCC activity was significantly reduced. Also, there was no difference in ADCC levels across the four vaccines, although NAbs and binding antibody titers were significantly higher in mRNA-vaccinated individuals. All evaluated vaccine platforms are inferior in inducing ADCC compared to natural infection with WT SARS-CoV-2. The inactivated virus-based vaccine can induce N-specific ADCC activity, but its relevance to clinical outcomes requires further investigation. Our data suggest that ADCC could be used to estimate the extra-neutralization level against COVID-19 and provides evidence that vaccination should focus on other Fc-effector functions besides NAbs. Also, the decreased susceptibility of the omicron variant to ADCC offers valuable guidance for forthcoming efforts to identify the specific targets of antibodies facilitating ADCC.We thank the virology research center at the National Institute of Health (VRC-NIH) for providing the plasmids used to generate SARS-CoV-2 pseudoviruses and for providing HEK293T cells. We also thank the UREP students who assisted in the blood samples collection and coordination: Tala Jamaleddin, Huda Abdul Hameed, Amira Elsharafi, Fatima AlHamaydeh, Bushra Abu Halawa, Hadiya Khalid, Nasrin Cusman, Maram Ali, Hamas Fouda, Salma Mohamud, and Reham Kamal. This study was supported by partial funds from grant #NPRP11S-1212-170092 awarded to Dr. Yassine. GKN would like to acknowledge that this work was made possible by WHO grant number COVID-19-22-43; QUCG-BRC-23/24-170, and grant number UREP29-026-3-004 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the authors' responsibility
Impact of diabetes mellitus on tuberculosis epidemiology in Indonesia: A mathematical modeling analysis.
We investigated and forecasted the impact of diabetes mellitus (DM) on tuberculosis (TB) epidemiology in Indonesia between 2020 and 2050. A recently-developed age-structured TB-DM dynamic mathematical model was utilized to assess the impact of DM on TB epidemiology. Model parameters were informed by systematic reviews and meta-analyses. Sensitivity and uncertainty analyses were conducted to assess robustness of predictions. The proportion of TB incident cases attributed to DM increased from 18.8% (95% uncertainty interval (UI): 12.6%-24.3%) in 2020, to 20.9% (95% UI: 14.7%-27.1%) in 2030, and 25.8% (95% UI: 17.7%-32.2%) in 2050. The proportion of TB-related deaths attributed to DM increased from 24.3% (95% UI: 18.7%-29.1%) in 2020, to 27.7% (95% UI: 22.4%-32.4%) in 2030, and 34.3% (95% UI: 27.6%-38.0%) in 2050. Most of the impact of DM on TB transmission has risen because of faster progression to TB disease, increased risk of reinfection, and increased infectiousness, with higher bacterial loads. Sensitivity and uncertainty analyses affirmed the predictions. TB-DM synergy is projected to increase in Indonesia over the next three decades with DM becoming a major driver of TB incidence and deaths. Joint TB-DM management and programs could offer significant reductions in TB incidence and mortality, making post-2015 End TB targets more feasible
HIV and herpes simplex virus type 2 epidemiological synergy: misguided observational evidence? A modelling study
»LJ« Artist book
The thesis paper deals with the artist book, an art form that has become a part of the university curriculum since the beginning of my university studies. It is most closely connected with the fields of sketch and photography. Both personl sketch and the field of photography have been of particular interest to me during my university years and I prepared an exhibition on the subject, presented by Faculty of Education Gallery. This thesis covers the historical and theoretical background of the artist book and maps the creation of my own artist book, an artistic superaddition titled LJ.
Some of the pioneers of the artist book are also mentioned, including Ed Ruscha, the author of the Twenty Six Gasoline Stations. He was one of the first artist to draw attention to the various artistic possibilities of this art form intertwining different graphic components including sketch, photography, font, paper characteristic, and other visual effects. Franc zagoričnik is presented as a native artist interested in the art form. He was a member of the OHO group, which reached the same conclusions as Ruscha in the 1970s.
The thesis places the artist book within the field of education, since this particular pedagogical approach has been shown to give the pupil freedom of choice and thus enrich his sensibilty to artistic expression. Pratical reasearch was conducted at a high school in Koper, while theoretical research heavily relied on the MGLC library, which is the only Slovene library to carry contemporary literature on this particular art form
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