scholarly journals On-demand, cell-free biomanufacturing of conjugate vaccines at the point-of-care

2019 ◽  
Author(s):  
Jessica C. Stark ◽  
Thapakorn Jaroentomeechai ◽  
Tyler D. Moeller ◽  
Rachel S. Dubner ◽  
Karen J. Hsu ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Point Of Care ◽  
Cold Chain ◽  
Conjugate Vaccines ◽  
Accelerate Development ◽  
Freeze Dried ◽  
Modular Technology ◽  
Independent Distribution ◽  
Schu S4 ◽  
Engineered Bacteria

SummaryConjugate vaccines are among the most effective methods for preventing bacterial infections, representing a promising strategy to combat drug-resistant pathogens. However, existing manufacturing approaches limit access to conjugate vaccines due to centralized production and cold chain distribution requirements. To address these limitations, we developed a modular technology forin vitrobioconjugatevaccine expression (iVAX) in portable, freeze-dried lysates from detoxified, nonpathogenicEscherichia coli. Upon rehydration, iVAX reactions synthesize clinically relevant doses of bioconjugate vaccines against diverse bacterial pathogens in one hour. We show that iVAX synthesized vaccines against the highly virulent pathogenFranciscella tularensissubsp.tularensis(type A) strain Schu S4 elicited pathogen-specific antibodies in mice at significantly higher levels compared to vaccines produced using engineered bacteria. The iVAX platform promises to accelerate development of new bioconjugate vaccines with increased access through refrigeration-independent distribution and point-of-care production.

scholarly journals On-demand biomanufacturing of protective conjugate vaccines

2021 ◽  
Vol 7 (6) ◽  
pp. eabe9444
Author(s):  
Jessica C. Stark ◽  
Thapakorn Jaroentomeechai ◽  
Tyler D. Moeller ◽  
Jasmine M. Hershewe ◽  
Katherine F. Warfel ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Cold Chain ◽  
Conjugate Vaccines ◽  
Accelerate Development ◽  
Freeze Dried ◽  
Modular Technology ◽  
Independent Distribution ◽  
Schu S4 ◽  
Limit Access

Conjugate vaccines are among the most effective methods for preventing bacterial infections. However, existing manufacturing approaches limit access to conjugate vaccines due to centralized production and cold chain distribution requirements. To address these limitations, we developed a modular technology for in vitro conjugate vaccine expression (iVAX) in portable, freeze-dried lysates from detoxified, nonpathogenic Escherichia coli. Upon rehydration, iVAX reactions synthesize clinically relevant doses of conjugate vaccines against diverse bacterial pathogens in 1 hour. We show that iVAX-synthesized vaccines against Francisella tularensis subsp. tularensis (type A) strain Schu S4 protected mice from lethal intranasal F. tularensis challenge. The iVAX platform promises to accelerate development of new conjugate vaccines with increased access through refrigeration-independent distribution and portable production.

Bacterial detection and differentiation via direct volatile organic compound sensing with surface enhanced Raman spectroscopy

2017 ◽  
Author(s):  
Caitlin S. DeJong ◽  
David I. Wang ◽  
Aleksandr Polyakov ◽  
Anita Rogacs ◽  
Steven J. Simske ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Bacterial Infections ◽  
Direct Detection ◽  
Point Of Care ◽  
Surface Enhanced Raman Spectroscopy ◽  
E Coli ◽  
Recent Emergence ◽  
Surface Enhanced ◽  
Volatile Organic ◽  
Surface Enhanced Raman

Through the direct detection of bacterial volatile organic compounds (VOCs), via surface enhanced Raman spectroscopy (SERS), we report here a reconfigurable assay for the identification and monitoring of bacteria. We demonstrate differentiation between highly clinically relevant organisms: <i>Escherichia coli</i>, <i>Enterobacter cloacae</i>, and <i>Serratia marcescens</i>. This is the first differentiation of bacteria via SERS of bacterial VOC signatures. The assay also detected as few as 10 CFU/ml of <i>E. coli</i> in under 12 hrs, and detected <i>E. coli</i> from whole human blood and human urine in 16 hrs at clinically relevant concentrations of 10<sup>3</sup> CFU/ml and 10<sup>4</sup> CFU/ml, respectively. In addition, the recent emergence of portable Raman spectrometers uniquely allows SERS to bring VOC detection to point-of-care settings for diagnosing bacterial infections.

Re-challenging antibiotic resistance with Daniel Berman

2020 ◽  
Author(s):  
Daniel Berman
Keyword(s):  
Bacterial Infections ◽  
Point Of Care ◽  
Healthcare Setting ◽  
Rapid Diagnostic Tests ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Drug Resistant Bacteria ◽  
Global Threat ◽  
The Right ◽  
Point Of Care Tests

How can we prevent the rise of resistance to antibiotics? In this video, Daniel Berman,  Nesta Challenges, discusses the global threat of AMR and how prizes like the Longitude Prize can foster the development of rapid diagnostic tests for bacterial infections, helping to contribute towards reducing the global threat of drug resistant bacteria. Daniel outlines how accelerating the development of rapid point-of-care tests will ensure that bacterial infections are treated with the most appropriate antibiotic, at the right time and in the right healthcare setting.

scholarly journals Emerging Options for the Diagnosis of Bacterial Infections and the Characterization of Antimicrobial Resistance

2021 ◽  
Vol 22 (1) ◽  
pp. 456
Author(s):  
Simone Rentschler ◽  
Lars Kaiser ◽  
Hans-Peter Deigner
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Point Of Care ◽  
Rapid Identification ◽  
Adequate Treatment ◽  
Resistance Patterns ◽  
Detection And Diagnosis ◽  
Patient Prognosis ◽  
Point Of Care Detection

Precise and rapid identification and characterization of pathogens and antimicrobial resistance patterns are critical for the adequate treatment of infections, which represent an increasing problem in intensive care medicine. The current situation remains far from satisfactory in terms of turnaround times and overall efficacy. Application of an ineffective antimicrobial agent or the unnecessary use of broad-spectrum antibiotics worsens the patient prognosis and further accelerates the generation of resistant mutants. Here, we provide an overview that includes an evaluation and comparison of existing tools used to diagnose bacterial infections, together with a consideration of the underlying molecular principles and technologies. Special emphasis is placed on emerging developments that may lead to significant improvements in point of care detection and diagnosis of multi-resistant pathogens, and new directions that may be used to guide antibiotic therapy.

Diagnostic tests for detecting Chlamydia trachomatis and Neisseria gonorrhoeae in rectal and pharyngeal specimens

2021 ◽  
Author(s):  
Paul C. Adamson ◽  
Jeffrey D. Klausner
Keyword(s):  
Chlamydia Trachomatis ◽  
Neisseria Gonorrhoeae ◽  
Bacterial Infections ◽  
Point Of Care ◽  
High Sensitivity ◽  
Population Level ◽  
The United States ◽  
Nucleic Acid Amplification ◽  
Point Of Care Test ◽  
Control And Prevention

Chlamydia trachomatis and Neisseria gonorrhoeae are two of the most often reported bacterial infections in the United States. The rectum and oropharynx are important anatomic sites of infection and can contribute to ongoing transmission. Nucleic acid amplification tests (NAATs) are the mainstays for the detection of C. trachomatis and N. gonorrhoeae infections owing to their high sensitivity and specificity. Several NAATs have been evaluated for testing in rectal and pharyngeal infections. A few assays recently received clearance by the Food and Drug Administration, including one point-of-care test. Those assays can be used for testing in symptomatic individuals, as well as for asymptomatic screening in certain patient populations. Routine screening for C. trachomatis in pharyngeal specimens is not recommended by the Centers for Disease Control and Prevention, though is often performed due to the use of multiplex assays. While expanding the types of settings for screening and using self-collected rectal and pharyngeal specimens can help to increase access and uptake of testing, additional research is needed to determine the potential benefits and costs associated with increased screening for rectal and pharyngeal C. trachomatis and N. gonorrhoeae infections on a population level.

scholarly journals Human Neutrophil Lipocalin as a Superior Diagnostic Means To Distinguish between Acute Bacterial and Viral Infections

2015 ◽  
Vol 22 (9) ◽  
pp. 1025-1032 ◽  
Author(s):  
Per Venge ◽  
Lena Douhan-Håkansson ◽  
Daniel Garwicz ◽  
Christer Peterson ◽  
Shengyuan Xu ◽  
...  
Keyword(s):  
Whole Blood ◽  
Human Neutrophil ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Response Times ◽  
Clinical Performance ◽  
Point Of Care ◽  
Signs And Symptoms ◽  
Healthy Controls ◽  
Acute Infections

ABSTRACTThe distinction between causes of acute infections is a major clinical challenge. Current biomarkers, however, are not sufficiently accurate. Human neutrophil lipocalin (HNL) concentrations in serum or whole blood activated by formyl-methionine-leucine-phenylalanine (fMLP) were shown to distinguish acute infections of bacterial or viral cause with high accuracy. The aim was therefore to compare the clinical performance of HNL with currently used biomarkers. Seven hundred twenty-five subjects (144 healthy controls and 581 patients with signs and symptoms of acute infections) were included in the study. C-reactive protein (CRP), the expression of CD64 on neutrophils, procalcitonin (PCT), and blood neutrophil counts were measured by established techniques, and HNL concentrations were measured in whole-blood samples after activation with fMLP. All tested biomarkers were elevated in bacterial as opposed to viral infections (P< 0.001). CRP, PCT, and CD64 expression in neutrophils was elevated in viral infections compared to healthy controls (P< 0.001). In the distinction between healthy controls and patients with bacterial infections, the areas under the receiver operating characteristic (ROC) curves were >0.85 for all biomarkers, whereas for the distinction between bacterial and viral infections, only HNL concentration in fMLP-activated whole blood showed an area under the ROC curve (AUROC) of >0.90 and superior clinical performance. The clinical performance of HNL in fMLP-activated whole blood was superior to current biomarkers and similar to previous results of HNL in serum. The procedure can be adopted for point-of-care testing with response times of <15 min.

Polysaccharide-Based Conjugate Vaccines for Enteric Bacterial Infections

2009 ◽  
pp. 489-496
Author(s):  
Shousun Szu ◽  
John Robbins ◽  
Rachel Schneerson ◽  
F Lin
Keyword(s):  
Bacterial Infections ◽  
Conjugate Vaccines

scholarly journals 725. Clinical Outcomes of Elderly Individuals Presenting with Acute Respiratory Infections

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S260-S260
Author(s):  
Allison Bloom ◽  
Sunil Suchindran ◽  
Micah T Mcclain
Keyword(s):  
Clinical Outcomes ◽  
Bacterial Infections ◽  
Respiratory Infections ◽  
Point Of Care ◽  
Predictive Ability ◽  
Elderly Subjects ◽  
Acute Respiratory Infections ◽  
Elderly Individuals ◽  
Increased Risk ◽  
Scoring Tool

Abstract Background Elderly individuals experience increased morbidity and mortality from acute respiratory infections (ARI), which are complicated by difficulties defining etiologies of ARI and risk-stratifying patients in order to guide care. A number of scoring tools have been developed to predict illness severity and patient outcome for proven pneumonia, however less is known about the use of such metrics for all causes of ARIs. Methods We analyzed risk factors, clinical course and major outcomes of individuals ≥60 years of age presenting to the emergency department with a clinical diagnosis of ARI over a 5-year period. Results Of the enrolled individuals 40 had proven viral infection and 52 proven bacterial infections, but 184 patients with clinically adjudicated ARI (67%) remained without a proven microbial etiology despite extensive workup. Age (71.5 vs. 65.9 years, P &lt; 0.001) and presence of cancer and heart failure were strongly predictive of illness severe enough to require hospital admission as compared with treatment in the outpatient setting. Of those with proven etiology, individuals with bacterial infection were more likely to require hospital and ICU admission (P &lt; 0.001). When applied to this study, a modified PORT score was found to correlate more closely with clinical outcome measures than a modified CURB-65 (r, 0.54 vs. 0.39). Jackson symptom scores, historically used for viral illness, were found to inversely correlate with outcomes (r, −0.34) and show potential for differentiating viral and bacterial etiologies (P = 0.02). Interestingly, a multivariate analysis showed that a novel scoring tool utilizing sex, heart rate, respiratory rate, blood pressure, BUN, glucose and presence of chronic lung disease and cancer was highly predictive of poor outcome in elderly subjects with all-cause ARI. Conclusion Elderly subjects are at increased risk for poor clinical outcomes from ARI and their clinical management remains challenging. However, modified PORT, CURB-65, Jackson symptom score, and a novel scoring tool presented herein all offer some predictive ability for all-cause ARI in elderly subjects. Such broadly applicable scoring metrics have the potential to assist in treatment and triage decisions at the point of care. Disclosures All authors: No reported disclosures.

scholarly journals A Convenient Colorimetric Bacteria Detection Method Utilizing Chitosan-Coated Magnetic Nanoparticles

Nanomaterials ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 92 ◽  
Author(s):  
Thao Nguyen Le ◽  
Tai Duc Tran ◽  
Moon Il Kim
Keyword(s):  
Magnetic Nanoparticles ◽  
Bacterial Infections ◽  
Colorimetric Assay ◽  
Point Of Care ◽  
Bacterial Cells ◽  
Diammonium Salt ◽  
Iron Oxide Magnetic Nanoparticles ◽  
Novel Strategy ◽  
Positively Charged ◽  
Timely Treatment

An effective novel strategy to detect bacteria is promising because it may improve human health by allowing early diagnosis and timely treatment of bacterial infections. Here, we report a simple, reliable, and economical colorimetric assay using the peroxidase-like activity of chitosan-coated iron oxide magnetic nanoparticles (CS-MNPs). When CS-MNPs are incubated with a sample containing bacterial cells such as the gram-negative Escherichia coli or the gram-positive Staphylococcus aureus, the negatively-charged bacterial membrane interacts with positively-charged chitosan on the surface of CS-MNPs, thus resulting in significant reduction of their peroxidase-like activity presumably by a hindrance in the accessibility of the negatively charged substrate, 2-2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) to the positively-charged CS-MNPs. This simple colorimetric strategy allowed the rapid detection of bacterial cells down to 104 CFU mL−1 by the naked eye and 102 CFU mL−1 by spectrophotometry within 10 min. Based on the results, we anticipate that the CS-MNPs-based assay has great potential for the on-site diagnosis of bacterial infections in facility-limited or point-of-care testing (POCT) environments.

‘Off–on’ switchable fluorescent probe for prompt and cost-efficient detection of bacteria

2019 ◽  
Vol 43 (33) ◽  
pp. 13094-13102
Author(s):  
Giorgia Giovannini ◽  
Vladimir Gubala ◽  
Andrew J. Hall
Keyword(s):  
Fluorescent Probe ◽  
Bacterial Infections ◽  
Point Of Care ◽  
Lab On A Chip ◽  
Human Samples ◽  
Efficient Detection ◽  
Prevention And Treatment ◽  
Cost Efficient

The rapid and straightforward detection of bacteria in food and human samples is becoming important, particularly in view of the development of point-of-care devices and lab-on-a-chip tools for prevention and treatment of bacterial infections.

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