Enhanced serodiagnostic potential of a fusion molecule consisting of Rv1793, Rv2628 and a truncated Rv2608 of Mycobacterium tuberculosis

Serodiagnosis of tuberculosis (TB) can be rapid, reliable and cost-effective if the issue of variable antibody responses of TB patients against different Mycobacterium tuberculosis (Mtb) antigens can be overcome by developing fusion proteins containing epitopes from multiple antigens of Mtb. In this study, Mtb antigens Rv1793, Rv2628, Rv2608 and a truncated variant produced by removing non-epitopic region from N-terminal of Rv2608 (tnRv2608), and the fusion protein Rv1793-Rv2628-tnRv2608 (TriFu64), were expressed in E. coli and purified. Plasma samples from TB patients characterized by sex, age and sputum/culture positivity, were used to compare the sensitivity of the single antigens with the fusion protein. Sensitivity of Rv1793, Rv2628 and Rv2608, was 27.8%, 39% and 36.3%, respectively. Truncation of Rv2608 increased sensitivity by approximately 35% in confirmed TB cases. Sensitivity of the fusion construct, TriFu64 increased to 66% with a specificity of 100%. Importantly, tnRv2608 was better able to detect sputum and culture negative patients, and this carried through to the fusion protein. We demonstrate that fusion of Mtb proteins ensures broad sensitivity across disease types, sex and age groups in a Pakistani population.

Download Full-text

Elevated Plasma Matrix Metalloproteinase-8 associates with Sputum Culture Positivity in Pulmonary Tuberculosis

10.1101/2021.11.15.21265734 ◽

2021 ◽

Author(s):

Naomi F Walker ◽

Farina Karim ◽

Mahomed-Yunus S Moosa ◽

Sashen Moodley ◽

Matilda Mazibuko ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Matrix Metalloproteinase ◽

Treatment Monitoring ◽

Elevated Plasma ◽

Tb Treatment ◽

Culture Positivity ◽

Potential Biomarker ◽

Culture Positive ◽

Culture Negative ◽

Procollagen Iii

Current methods for tuberculosis (TB) treatment monitoring are suboptimal. We evaluated plasma matrix metalloproteinase (MMP) and procollagen III N-terminal propeptide concentrations before and during TB treatment as biomarkers. Plasma MMP-1, -8 and -10 significantly decreased during treatment. Plasma MMP-8 was increased in sputum Mycobacterium tuberculosis culture positive relative to culture negative participants, prior to (median 4609 pg/ml, IQR 2353-9048 vs 775 pg/ml, IQR 551-4920, p=0.019) and after 6 months (median 3650, IQR 1214-3888 vs 720, IQR 551-1321, p=0.008) of TB treatment. Consequently, plasma MMP-8 is a potential biomarker to enhance TB treatment monitoring and screen for possible culture positivity.

Download Full-text

Mycobacterium tuberculosis Ag85b:hfcγ1 recombinant fusion protein as a selective receptor-dependent delivery system for antigen presentation

Microbial Pathogenesis ◽

10.1016/j.micpath.2019.01.045 ◽

2019 ◽

Vol 129 ◽

pp. 68-73 ◽

Cited By ~ 3

Author(s):

Mohsen Karbalaei Zadeh Babaki ◽

Mahboubeh Taghiabadi ◽

Saman Soleimanpour ◽

Masoud Saleh Moghadam ◽

Arman Mosavat ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Fusion Protein ◽

Antigen Presentation ◽

Delivery System ◽

Recombinant Fusion Protein

Download Full-text

Current and Future Pathotyping Platforms for Plasmodiophora brassicae in Canada

Plants ◽

10.3390/plants10071446 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1446

Author(s):

Heather H. Tso ◽

Leonardo Galindo-González ◽

Stephen E. Strelkov

Keyword(s):

Crop Production ◽

Plasmodiophora Brassicae ◽

Cost Effective ◽

Turnaround Time ◽

Molecular Techniques ◽

Differential Set ◽

Management Plans ◽

Increased Sensitivity ◽

Phenotypic Methods ◽

Important Disease

Clubroot, caused by Plasmodiophora brassicae, is one of the most detrimental threats to crucifers worldwide and has emerged as an important disease of canola (Brassica napus) in Canada. At present, pathotypes are distinguished phenotypically by their virulence patterns on host differential sets, including the systems of Williams, Somé et al., the European Clubroot Differential set, and most recently the Canadian Clubroot Differential set and the Sinitic Clubroot Differential set. Although these are frequently used because of their simplicity of application, they are time-consuming, labor-intensive, and can lack sensitivity. Early, preventative pathotype detection is imperative to maximize productivity and promote sustainable crop production. The decreased turnaround time and increased sensitivity and specificity of genotypic pathotyping will be valuable for the development of integrated clubroot management plans, and interest in molecular techniques to complement phenotypic methods is increasing. This review provides a synopsis of current and future molecular pathotyping platforms for P. brassicae and aims to provide information on techniques that may be most suitable for the development of rapid, reliable, and cost-effective pathotyping assays.

Download Full-text

Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein induces genetically and antigenically diverse antibody responses

Immunity ◽

10.1016/j.immuni.2021.03.004 ◽

2021 ◽

Author(s):

Maryam Mukhamedova ◽

Daniel Wrapp ◽

Chen-Hsiang Shen ◽

Morgan S.A. Gilman ◽

Tracy J. Ruckwardt ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Fusion Protein ◽

Antibody Responses ◽

Virus Fusion ◽

Syncytial Virus

Download Full-text

Association Between Diabetic Foot Infection Wound Culture Positivity and 1-Year Admission for Invasive Infection: A Multi-Center Cohort Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab172 ◽

2021 ◽

Author(s):

Westyn Branch-Elliman ◽

Daniel Sturgeon ◽

Adolf W Karchmer ◽

Hillary J Mull

Keyword(s):

Diabetic Foot ◽

Systemic Infection ◽

Causative Organism ◽

Invasive Infection ◽

Diabetic Foot Ulcers ◽

Diabetic Foot Infections ◽

Culture Positivity ◽

Wound Culture ◽

Culture Positive ◽

Culture Negative

Abstract Inpatients with culture-positive diabetic foot infections are at elevated risk for subsequent invasive infection with the same causative organism. In outpatients with index diabetic foot ulcers, we found that wound culture positivity was independently associated with increased odds of 1-year admission for systemic infection when compared to culture-negative wounds.

Download Full-text

Ethnic Specific body fat percent prediction equation as surrogate marker of obesity in Ethiopian adults

Journal of Health Population and Nutrition ◽

10.1186/s41043-021-00224-3 ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Makeda Sinaga ◽

Melese Sinaga Teshome ◽

Tilhun Yemane ◽

Elsah Tegene ◽

David Lindtsrom ◽

...

Keyword(s):

Body Fat ◽

Age Groups ◽

Surrogate Marker ◽

Cost Effective ◽

Prediction Equation ◽

Prediction Equations ◽

Altman Plot ◽

Cross Sectional ◽

Bland Altman Plot ◽

Body Fat Percent

Abstract Background Application of advanced body composition measurement methods is not practical in developing countries context due to cost and unavailability of facilities. This study generated ethnic specific body fat percent prediction equation for Ethiopian adults using appropriate data. Methods A cross-sectional study was carried ifrom February to April 2015 among 704 randomly selected adult employees of Jimma University. Ethnic specific Ethiopian body fat percent (BF%) prediction equation was developed using a multivariable linear regression model with measured BF% as dependent variable and age, sex, and body mass index as predictor variables. Agreement between fat percent measured using air displacement plethysmography and body fat percent estimated using Caucasian prediction equations was determined using Bland Altman plot. Results Comparison of ADP measured and predicted BF% showed that Caucasian prediction equation underestimated body fat percent among Ethiopian adults by 6.78% (P < 0.0001). This finding is consistent across all age groups and ethnicities in both sexes. Bland Altman plot did not show agreement between ADP and Caucasian prediction equation (mean difference = 6.7825) and some of the points are outside 95% confidence interval. The caucasian prediction equation significantly underestimates body fat percent in Ethiopian adults, which is consistent across all ethnic groups in the sample. The study developed Ethnic specific BF% prediction equations for Ethiopian adults. Conclusion The Caucasian prediction equation significantly underestimates body fat percent among Ethiopian adults regardless of ethnicity. Ethiopian ethnic-specific prediction equation can be used as a very simple, cheap, and cost-effective alternative for estimating body fat percent among Ethiopian adults for health care provision in the prevention of obesity and related morbidities and for research purposes.

Download Full-text

How effective and cost-effective is water fluoridation for adults? Protocol for a 10-year retrospective cohort study

BDJ Open ◽

10.1038/s41405-021-00062-9 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Deborah Moore ◽

Thomas Allen ◽

Stephen Birch ◽

Martin Tickle ◽

Tanya Walsh ◽

...

Keyword(s):

Cohort Study ◽

Cost Effectiveness ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Dental Treatment ◽

Age Groups ◽

Cost Effective ◽

Tooth Decay ◽

Service Utilisation ◽

Water Fluoridation

Abstract Background Tooth decay can cause pain, sleepless nights and loss of productive workdays. Fluoridation of drinking water was identified in the 1940s as a cost-effective method of prevention. In the mid-1970s, fluoride toothpastes became widely available. Since then, in high-income countries the prevalence of tooth decay in children has reduced whilst natural tooth retention in older age groups has increased. Most water fluoridation research was carried out before these dramatic changes in fluoride availability and oral health. Furthermore, there is a paucity of evidence in adults. The aim of this study is to assess the clinical and cost-effectiveness of water fluoridation in preventing invasive dental treatment in adults and adolescents aged over 12. Methods/design Retrospective cohort study using 10 years of routinely available dental treatment data. Individuals exposed to water fluoridation will be identified by sampled water fluoride concentration linked to place of residence. Outcomes will be based on the number of invasive dental treatments received per participant (fillings, extractions, root canal treatments). A generalised linear model with clustering by local authority area will be used for analysis. The model will include area level propensity scores and individual-level covariates. The economic evaluation will focus on (1) cost-effectiveness as assessed by the water fluoridation mean cost per invasive treatment avoided and (2) a return on investment from the public sector perspective, capturing the change in cost of dental service utilisation resulting from investment in water fluoridation. Discussions There is a well-recognised need for contemporary evidence regarding the effectiveness and cost-effectiveness of water fluoridation, particularly for adults. The absence of such evidence for all age groups may lead to an underestimation of the potential benefits of a population-wide, rather than targeted, fluoride delivery programme. This study will utilise a pragmatic design to address the information needs of policy makers in a timely manner.

Download Full-text

Evaluation of Two Tetravalent (ACYW135) Meningococcal Vaccines in Infants and Small Children: A Clinical Study Comparing Immunogenicity of O-Acetyl-Negative and O-Acetyl-Positive Group C Polysaccharides

PEDIATRICS ◽

10.1542/peds.76.1.91 ◽

1985 ◽

Vol 76 (1) ◽

pp. 91-96

Author(s):

Heikki Peltola ◽

Assad Safary ◽

Helena Käyhty ◽

Viena Karanko ◽

Francis E. André

Keyword(s):

Clinical Study ◽

Elevated Temperatures ◽

Age Groups ◽

Antibody Responses ◽

Meningococcal Vaccine ◽

Small Children ◽

Positive Group ◽

Systemic Reactions ◽

Antibody Titers ◽

Group A

Two different tetravalent polysaccharide vaccines against group A, C, Y, and W135 meningococci were given to 118 infants aged 6 to 23 months; the same vaccines were administered in a second dose 12 months later to those infants aged 6 to 11 months at first vaccination. Forty of the infants received vaccine containing the nonacetylated group C polysaccharide C(OAc-) and 78 the acetylated group C polysaccharide C(OAc+) together with group A, Y, and W135 polysaccharides. All polysaccharides, at a dose of 30 µg, induced antibody responses after administration of both vaccines in all age groups although the responses were better in the older infants. Acetylation of the sialic acid of the group C polysaccharide did not significantly influence the response. Rapid decreases in the antibody titers after the first vaccination stressed the need for one or more revaccinations. Vaccination elicited mild local and systemic reactions. Elevated temperatures were more common in the youngest infants but only four developed fever exceeding 38.5°C (101.3°F). We conclude that tetravalent (ACYW135) meningococcal vaccine is safe and immunologically effective in children younger than age 2 years. However, revaccinations may be required to maintain immunity.

Download Full-text

Fc-Based Recombinant Henipavirus Vaccines Elicit Broad Neutralizing Antibody Responses in Mice

Viruses ◽

10.3390/v12040480 ◽

2020 ◽

Vol 12 (4) ◽

pp. 480 ◽

Cited By ~ 3

Author(s):

Yaohui Li ◽

Ruihua Li ◽

Meirong Wang ◽

Yujiao Liu ◽

Ying Yin ◽

...

Keyword(s):

Antibody Response ◽

Fusion Protein ◽

G Protein ◽

G Proteins ◽

Hendra Virus ◽

Antibody Responses ◽

Asia Pacific ◽

Highly Pathogenic ◽

Bivalent Vaccine ◽

Tetravalent Vaccine

The genus Henipavirus (HNVs) includes two fatal viruses, namely Nipah virus (NiV) and Hendra virus (HeV). Since 1994, NiV and HeV have been endemic to the Asia–Pacific region and responsible for more than 600 cases of infections. Two emerging HNVs, Ghana virus (GhV) and Mojiang virus (MojV), are speculated to be associated with unrecognized human diseases in Africa and China, respectively. Despite many efforts to develop vaccines against henipaviral diseases, there is presently no licensed human vaccine. As HNVs are highly pathogenic and diverse, it is necessary to develop universal vaccines to prevent future outbreaks. The attachment enveloped glycoprotein (G protein) of HNVs mediates HNV attachment to the host cell’s surface receptors. G proteins have been used as a protective antigen in many vaccine candidates for HNVs. We performed quantitative studies on the antibody responses elicited by the G proteins of NiV, HeV, GhV, and MojV. We found that the G proteins of NiV and HeV elicited only a limited cross-reactive antibody response. Further, there was no cross-protection between MojV, GhV, and highly pathogenic HNVs. We then constructed a bivalent vaccine where the G proteins of NiV and HeV were fused with the human IgG1 Fc domain. The immunogenicity of the bivalent vaccine was compared with that of monovalent vaccines. Our results revealed that the Fc-based bivalent vaccine elicited a potent antibody response against both NiV and HeV. We also constructed a tetravalent Fc heterodimer fusion protein that contains the G protein domains of four HNVs. Immunization with the tetravalent vaccine elicited broad antibody responses against NiV, HeV, GhV, and MojV in mice, indicating compatibility among the four antigens in the Fc-fusion protein. These data suggest that our novel bivalent and tetravalent Fc-fusion proteins may be efficient candidates to prevent HNV infection.

Download Full-text