scholarly journals Development of a Monocyte Activation Test as an Alternative to the Rabbit Pyrogen Test for Mono- and Multi-Component Shigella GMMA-Based Vaccines

2021 ◽  
Vol 9 (7) ◽  
pp. 1375
Author(s):  
Danielle Carson ◽  
Sophie Myhill ◽  
Elena Palmieri ◽  
Francesca Necchi ◽  
Sjoerd Rijpkema ◽  
...  
Keyword(s):  
Adverse Reactions ◽  
Drug Product ◽  
Gram Negative Bacteria ◽  
European Pharmacopoeia ◽  
Monocyte Activation ◽  
Gram Negative ◽  
Safety Testing ◽  
Activation Test ◽  
Batch Release ◽  
Membrane Antigens

Generalised modules for membrane antigens (GMMA)-based vaccines comprise the outer membrane from genetically modified Gram-negative bacteria containing membrane proteins, phospholipids and lipopolysaccharides. Some lipoproteins and lipopolysaccharides are pyrogens; thus, GMMA-based vaccines are intrinsically pyrogenic. It is important to control the pyrogenic content of biological medicines, including vaccines, to prevent adverse reactions such as febrile responses. The rabbit pyrogen test (RPT) and bacterial endotoxin test (BET) are the most commonly employed safety assays used to detect pyrogens. However, both tests are tailored for detecting pyrogenic contaminants and have considerable limitations when measuring the pyrogen content of inherently pyrogenic products. We report the adaptation of the monocyte activation test (MAT) as an alternative to the RPT for monitoring the pyrogenicity of Shigella GMMA-based vaccines. The European Pharmacopoeia endorses three MAT methods (A–C). Of these, method C, the reference lot comparison test, was identified as the most suitable. This method was evaluated with different reference materials to ensure parallelism and consistency for a mono- and multi-component Shigella GMMA vaccine. We demonstrate the drug substance as a promising reference material for safety testing of the matched drug product. Our results support the implementation of MAT as an alternative to the RPT and use of the defined parameters can be extended to GMMA-based vaccines currently in development, aiding vaccine batch release.

Newer Quinolones in the Treatment of Continuous Ambulatory Peritoneal Dialysis (CAPD) Related Infections

1990 ◽  
Vol 10 (2) ◽  
pp. 127-133 ◽  
Author(s):  
Paul Nikolaidis
Keyword(s):  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Adverse Reactions ◽  
Antimicrobial Agents ◽  
Hospital Staff ◽  
Gram Negative Bacteria ◽  
Promising Alternative ◽  
Gram Negative ◽  
Dosing Intervals ◽  
Good Oral Bioavailability

Newer fluoroquinolones such as ciprofloxacin, pefloxacin, ofloxacin, enoxacin, and fleroxacin are potent antimicrobial agents against many gram-negative bacteria, including Pseudomonas aeruginosa species and staphylococci-sensitive or resistant to methicillin. They are almost completely absorbed when given orally, reaching therapeutic plasma and dialysate concentrations, and their long half lives permit infrequent dosing intervals. Clinical studies on fluoroquinolones efficacy in continuous ambulatory peritoneal dialysis (CAPD) infections, although not extensive, demonstrate good results. They are well tolerated and the adverse reactions, consisting mainly of gastrointestinal disturbance, were uncommon, mild, and reversible. The fluoroquinolones offer a promising alternative to standard parenteral treatments in CAPD patients, while their good oral bioavailability makes them attractive and convenient for both patients and hospital staff. However, they must be used with caution until we have more information and gain further experience.

scholarly journals Evaluation of the monocyte activation test for the safety testing of meningococcal B vaccine Bexsero: A collaborative study

Vaccine ◽  
2019 ◽  
Vol 37 (29) ◽  
pp. 3761-3769 ◽  
Author(s):  
Lucy Studholme ◽  
Janet Sutherland ◽  
Trusha Desai ◽  
Jason Hockley ◽  
Rory Care ◽  
...  
Keyword(s):  
Collaborative Study ◽  
Monocyte Activation ◽  
Safety Testing ◽  
Activation Test

scholarly journals GMMA-Based Vaccines: The Known and The Unknown

2021 ◽  
Vol 12 ◽  
Author(s):  
Francesca Mancini ◽  
Francesca Micoli ◽  
Francesca Necchi ◽  
Mariagrazia Pizza ◽  
Francesco Berlanda Scorza ◽  
...  
Keyword(s):  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Gram Negative Bacteria ◽  
Protein Antigens ◽  
Vaccine Platform ◽  
Gram Negative ◽  
Particulate Size ◽  
Membrane Antigens ◽  
Genetically Manipulated ◽  
High Immunogenicity

Generalized Modules for Membrane Antigens (GMMA) are outer membrane vesicles derived from Gram-negative bacteria engineered to provide an over-vesiculating phenotype, which represent an attractive platform for the design of affordable vaccines. GMMA can be further genetically manipulated to modulate the risk of systemic reactogenicity and to act as delivery system for heterologous polysaccharide or protein antigens. GMMA are able to induce strong immunogenicity and protection in animal challenge models, and to be well-tolerated and immunogenic in clinical studies. The high immunogenicity could be ascribed to their particulate size, to their ability to present to the immune system multiple antigens in a natural conformation which mimics the bacterial environment, as well as to their intrinsic self-adjuvanticity. However, GMMA mechanism of action and the role in adjuvanticity are still unclear and need further investigation. In this review, we discuss progresses in the development of the GMMA vaccine platform, highlighting successful applications and identifying knowledge gaps and potential challenges.

Applicability of the Monocyte Activation Test (MAT) in the Quality Control of the 17DD Yellow Fever Vaccine

2018 ◽  
Vol 46 (1) ◽  
pp. 23-37
Author(s):  
Katherine Antunes de Mattos ◽  
Elaine Cristina Azevedo Navega ◽  
Vitor Fernandes Silva ◽  
Alessandra Santos Almeida ◽  
Cristiane Caldeira da Silva ◽  
...  
Keyword(s):  
Quality Control ◽  
Yellow Fever ◽  
Lipoteichoic Acid ◽  
Yellow Fever Vaccine ◽  
European Pharmacopoeia ◽  
Monocyte Activation ◽  
Activation Test ◽  
Effective Implementation ◽  
Animal Use ◽  
The Three Rs

The need for alternatives to animal use in pyrogen testing has been driven by the Three Rs concept. This has resulted in the inclusion of the monocyte activation test (MAT) in the European Pharmacopoeia, 2010. However, some technical and regulatory obstacles must be overcome to ensure the effective implementation of the MAT by the industry, especially for the testing of biological products. The yellow fever (YF) vaccine (17DD-YFV) was chosen for evaluation in this study, in view of: a) the 2016–2018 outbreak of YF in Brazil; b) the increase in demand for 17DD-YFV doses; c) the complex production process with live attenuated virus; d) the presence of possible test interference factors, such as residual process components (e.g. ovalbumin); and e) the need for the investigation of other pyrogens that are not detectable by the methods prescribed in the YF vaccine monograph. The product-specific testing was carried out by using cryopreserved and fresh whole blood, and IL-6 and IL-1β levels were used as the marker readouts. After assessing the applicability of the MAT on a 1:10 dilution of 17DD-YFV, endotoxin and non-endotoxin pyrogens were quantified in spiked batches, by using the lipopolysaccharide and lipoteichoic acid standards, respectively. The quantitative analysis demonstrated the correlation between the MAT and the Limulus amoebocyte lysate (LAL) assays, with respect to the limits of endotoxin recovery in spiked batches and the detection of no pyrogenic contamination in commercial batches of 17DD-YFV. The data demonstrated the applicability of the MAT for 17DD-YFV pyrogen testing, and as an alternative method that can contribute to biological quality control studies.

scholarly journals Development and validation of a monocyte activation test for the control/safety testing of an OMV-based meningococcal B vaccine

Vaccine ◽  
2019 ◽  
Vol 37 (29) ◽  
pp. 3747-3753 ◽  
Author(s):  
Caroline Vipond ◽  
Janet Sutherland ◽  
Karin Nordgren ◽  
George Kemp ◽  
Alan Heath ◽  
...  
Keyword(s):  
Monocyte Activation ◽  
Safety Testing ◽  
Activation Test ◽  
Development And Validation

Bacterial-Mucosal Cell Junctional Complexes

1974 ◽  
Vol 32 ◽  
pp. 144-145
Author(s):  
Roger C. Wagner
Keyword(s):  
Intestinal Wall ◽  
Rat Colon ◽  
Mucosal Cell ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Mucosal Cells ◽  
Mucosal Lining ◽  
Degenerative Alterations ◽  
Junctional Complexes ◽  
Intestinal Mucosal Cells

Bacteria exhibit the ability to adhere to the apical surfaces of intestinal mucosal cells. These attachments either precede invasion of the intestinal wall by the bacteria with accompanying inflammation and degeneration of the mucosa or represent permanent anchoring sites where the bacteria never totally penetrate the mucosal cells.Endemic gram negative bacteria were found attached to the surface of mucosal cells lining the walls of crypts in the rat colon. The bacteria did not intrude deeper than 0.5 urn into the mucosal cells and no degenerative alterations were detectable in the mucosal lining.

Rapid demonstration of septic or infectious arthritis due to Gram-negative bacteria

1992 ◽  
Vol 50 (1) ◽  
pp. 686-687
Author(s):  
Jacob S. Hanker ◽  
Paul R. Gross ◽  
Beverly L. Giammara
Keyword(s):  
Chronic Arthritis ◽  
Blood Cultures ◽  
Gram Negative Bacteria ◽  
Infectious Arthritis ◽  
Bacterial Arthritis ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria

Blood cultures are positive in approximately only 50 per cent of the patients with nongonococcal bacterial infectious arthritis and about 20 per cent of those with gonococcal arthritis. But the concept that gram-negative bacteria could be involved even in chronic arthritis is well-supported. Gram stains are more definitive in staphylococcal arthritis caused by gram-positive bacteria than in bacterial arthritis due to gram-negative bacteria. In the latter situation where gram-negative bacilli are the problem, Gram stains are helpful for 50% of the patients; they are only helpful for 25% of the patients, however, where gram-negative gonococci are the problem. In arthritis due to gram-positive Staphylococci. Gramstained smears are positive for 75% of the patients.

Ultrastructure of periplasmic bodies in gram-negative bacteria

1990 ◽  
Vol 48 (3) ◽  
pp. 640-641
Author(s):  
Xie Nianming ◽  
Ding Shaoqing ◽  
Wang Luping ◽  
Yuan Zenglin ◽  
Zhan Guolai ◽  
...  
Keyword(s):  
Electron Microscope ◽  
Campylobacter Jejuni ◽  
Proteus Mirabilis ◽  
Shigella Flexneri ◽  
Morphological Description ◽  
Gram Negative Bacteria ◽  
Periplasmic Space ◽  
Clostridium Tetani ◽  
Gram Negative ◽  
Brucella Canis

Perhaps the data about periplasmic enzymes are obtained through biochemical methods but lack of morphological description. We have proved the existence of periplasmic bodies by electron microscope and described their ultrastructures. We hope this report may draw the attention of biochemists and mrophologists to collaborate on researches in periplasmic enzymes or periplasmic bodies with each other.One or more independent bodies may be seen in the periplasmic space between outer and inner membranes of Gram-negative bacteria, which we called periplasmic bodies. The periplasmic bodies have been found in seven species of bacteria at least, including the Pseudomonas aeroginosa. Shigella flexneri, Echerichia coli. Yersinia pestis, Campylobacter jejuni, Proteus mirabilis, Clostridium tetani. Vibrio cholerae and Brucella canis.

Dual stain kit for the microscopic gram classification of ocular infection bacteria

1993 ◽  
Vol 51 ◽  
pp. 248-249
Author(s):  
Jacob S. Hanker ◽  
Dale N. Holdren ◽  
Kenneth L. Cohen ◽  
Beverly L. Giammara
Keyword(s):  
Contact Lenses ◽  
Ocular Infection ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Gram Staining ◽  
Ocular Infections ◽  
Different Types ◽  
Culture Positive ◽  
Increased Susceptibility

Keratitis and conjunctivitis (infections of the cornea or conjunctiva) are ocular infections caused by various bacteria, fungi, viruses or parasites; bacteria, however, are usually prominent. Systemic conditions such as alcoholism, diabetes, debilitating disease, AIDS and immunosuppressive therapy can lead to increased susceptibility but trauma and contact lens use are very important factors. Gram-negative bacteria are most frequently cultured in these situations and Pseudomonas aeruginosa is most usually isolated from culture-positive ulcers of patients using contact lenses. Smears for staining can be obtained with a special swab or spatula and Gram staining frequently guides choice of a therapeutic rinse prior to the report of the culture results upon which specific antibiotic therapy is based. In some cases staining of the direct smear may be diagnostic in situations where the culture will not grow. In these cases different types of stains occasionally assist in guiding therapy.

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