Background In the pre-clinical phase, SARS-CoV-2 vaccines were tested in animal models, including exposure trials, to investigate protection against SARS-CoV-2. These studies paved the way for clinical development. The objective of our review was to provide an overview of published animal exposure results, focussing on the capacity of vaccines to reduce/prevent viral shedding. Method Using Medline

Staphylococcus aureus is an important human opportunistic pathogen that can have a major influence on public health. Here, we aimed to evaluate different aspects of the immune response to a novel multi-epitope fusion protein (HMS) based on HlaH35L, MntC, and SACOL0723 proteins in comparison to the individual antigens. For this purpose, specific total IgG, IgG1, and IgG2a isotypes and the cytokines

The HIV-1 derived gp145 protein is being investigated by research groups as preclinical studies have shown high promise for this protein as a vaccine against HIV. However, one of the main challenges with manufacturing this promising protein has been ascribed to the low yield obtained in mammalian cell cultures. Significant improvements in gp145 production are needed to address this issue to test the

Background Manufacturing of human Mesenchymal Stromal Cells as advanced therapy medicinal product (ATMP) for clinical use involves an ex vivo expansion, which leads to a risk of contamination by microbiological agents. Even if manufacturing under Good Manufacturing Practice (GMP) license minimizes this risk, contamination of cell cultures by mycoplasmas still represents a widespread problem. Furthermore

Shigellosis, a diarrheal disorder caused by an entero-invasive bacterium Shigella, is a major concern among children often leading to mortality. As most of these strains have developed universal antibiotic resistance, the development of a vaccine is crucial in combating the infection. The O-specific polysaccharide (O-PSs) from S. flexneri type 2a is considered to be the major disease-causing antigen

Brucella is an infectious disease with difficult treatment faced with drug resistance and recurrence of infection. Despite advances in the development of effective vaccines against brucellosis infections, there is still a need for more effective vaccine against brucellosis. In this study, we developed a nanovaccine for delivery of lipopolysaccharide Brucella melitensis antigen to the immune system

Coinfection of Leishmania with bacteria, viruses, protozoans, and nematodes alter the immune system of the host, thereby influencing the disease outcomes. Here, we have determined the immunogenic property and protective efficacy of the cross-reactive molecule HSP60 of filarial parasite B. malayi against the L. donovani in BALB/c mice. Parasitological parameters results showed a significant decrease

Virus removal filtration processes in biopharmaceutical manufacturing are developed, optimized and validated for viral clearance using laboratory scale filters. Thus, the scalability of these filters is critical for accurately extrapolating filtration performance and reliably extending viral clearance to manufacturing scale. Virus removal filter manufacturers generally validate scalability of filtration

Porcine LFBKαVβ6 cells have been successfully used for diagnostics and propagation of all FMDV serotypes/subtypes. Unfortunately, after initial characterization, these cells showed contamination with bovine viral diarrhea virus (BVDV), a non-cytopathic adventitious agent. Persistent infection with BVDV could interfere with diagnostic tests and, also prevent consideration for other uses, i.e., vaccine

ABP 798 is a biosimilar to Rituxan® (rituximab reference product [RP]). Non-clinical assessments relevant to the primary and secondary mechanisms of action (MOA) contribute to the totality of the evidence (TOE) in supporting biosimilarity and are critical in providing scientific evidence for extrapolation of indications. Similarity of ABP 798 with rituximab RP was investigated across a range of biological

Tuberculosis (TB) is one of the top 10 causes of death in humans worldwide. The most important causative agents of TB are bacteria from the Mycobacterium tuberculosis complex (MTC), although nontuberculous mycobacteria (NTM) can also cause similar infections. The ability to identify and differentiate MTC isolates from NTM is important for the selection of the correct antimicrobial therapy. Immunochromatographic

Xenogenic cell-based therapeutic products are expected to alleviate the chronic shortage of human donor organs. For example, porcine islet cell products are currently under development for the treatment of human diabetes. As porcine cells possess endogenous retrovirus (PERV), which can replicate in human cells in vitro, the potential transmission of PERV has raised concerns in the case of products

The European Directorate for the Quality of Medicines & HealthCare (EDQM) has run proficiency testing schemes on the detection of viral contaminants in human plasma pools by nucleic-acid amplification techniques since 1999 for hepatitis C virus and since 2004 for parvovirus B19. A retrospective analysis was performed to assess their impact and identify trends and progress in the results obtained by

The rabbit pyrogen test (RPT) is a safety test conducted as a part of mandatory requirements of regulatory agencies. RPT is currently performed for routine quality control (QC) by manufacturers and for national lot release of biological products, such as plasma-derived products. However, RPT involves the use of many rabbits, counter to the international efforts to minimize the use of animals in research

Batch release testing for human and veterinary tetanus vaccines still relies heavily on methods that involve animals, particularly for potency testing. The quantity and quality of tetanus antigen present in these products is of utmost importance for product safety and clinical effect. Immunochemical methods that measure consistency of antigen content and quality, potentially as an indicator of potency

The objective of this study was to determine how the theoretical values of the extinction coefficient (EC) compares to the experimentally determined extinction coefficient for a large set of biotherapeutic proteins measured by the Edelhoch method. We have performed extensive analysis based on over 176 observations covering 19 different types of molecules from different structural classes covering mAbs

Cell cultures have provided an ideal habitat for a wide variety of Mycoplasma and Acholeplasma species since the earliest days of in-vitro culture. The possibility of contamination with Spiroplasma species was addressed by Regulatory Authorities due to the increased commercial use of insect cells, recognising that Spiroplasmas have been isolated from many types of arthropod and also that insect cell

A natural biodegradable polymer, polyhydroxyalkanoate (PHA), was adjuvanted with a vaccine seed to observe the biomaterial's ability in enhancing an immune response in rats. The adjuvant potential of PHA was tested using the whole-killed Pasteurella multocida B:2 (PMB2) vaccine in Sprague Dawley (SD) rats to detect changes in serum immunoglobulin G (IgG) and immunoglobulin M (IgM) responses. A common

The International Alliance for Biological Standardization and the Coalition for Epidemic Preparedness Innovations organized a joint webinar on the use of platform technologies for vaccine development. To tackle new emerging infectious diseases, including SARS-CoV-2, rapid response platforms, using the same basic components as a backbone, yet adaptable for use against different pathogens by inserting

Duck viral enteritis is an acute, contagious infection of Anatidae family members. The disease is caused by Anatid herpesvirus 1 (AnHV-1). The infection of AnHV-1 is controlled by vaccination to the flock with chick embryo adapted attenuated vaccine in developed countries. However, its economic impact in developing countries is substantial and there is a need to understand the cell culture spectrum

To examine the contribution that field efficacy studies made to the assessment of marketing authorisation (MA) applications, a retrospective analysis was conducted for 100 veterinary vaccines that had been evaluated by the European Medicines Agency (EMA) between 1996 and 2017. For 52 veterinary vaccines, scrutiny of the European Public Assessment Report (EPAR) and/or the summary of product characteristics

Many clinical studies in paediatric inflammatory bowel diseases (IBD) use infliximab trough level (IFX-TL) and detection of antibody against infliximab (ATI). Hence, comparison of commercially available assays is needed in paediatric samples to assess their reliability and their comparability. We measured IFX-TL and ATI-TL in sera samples of 53 IBD children using three ELISA kits: Lisa-Tracker® Duo

CTAB and DOC are used as reagents in the purification of Hib polysaccharide. Polysaccharide is purified by precipitation with CTAB from fermented broth followed by solvent extraction and DOC is used to remove the protein impurities. The reagents used in the purification process should be removed from the product as per regulatory requirements. These two residual reagents can be easily identified and

Astragaloside VII (AST-VII), a major cycloartane saponin isolated from Turkish Astragalus species, turned out to be one of the most active metabolites demonstrating Th1/Th2 balanced immune response. As Quillaja saponins are extensively used in adjuvant systems, this study made an attempt to improve AST-VII based adjuvant systems by using different immunostimulatory/delivery agents (monophosphoryllipid

Although the immunization against swine fever (SF) is compulsory in China, it has still emerged in several areas at times. Herein, this study was conducted to develop an antibody vaccine which can clear the classical swine fever virus (CSFV) immediately after the pathogen invasion. Bovine viral diarrhoea virus (BVDV) infectious cDNA clone pASH28 was used to express a single-chain fragment variable

Systemic Lupus Erythematosus (SLE) is an autoimmune inflammatory condition with a wide spectrum of disease manifestations and severities, resulting in significant morbidity and mortality. The aetiopathogenesis of SLE is complex. Young women and certain ethnicities are commonly affected, suggesting a significant hormonal and genetic influence. Diverse immunological abnormalities have been described

A new, simple and rapid method for the quantitative determination of the antimicrobial preservative 2-phenoxyethanol, based on reverse phase ultra-high-performance liquid chromatography has been developed. The validation was performed according the ICH Q2 guideline “Validation of Analytical Procedures”. The desired chromatographic separation was achieved on a Waters Symmetry C18 (150 × 4.6 mm, 5 μm)

The quality of antivenom is governed by its safety and efficacy profiles. These quality characteristics are much influenced by the purity of antivenom content. Rigorous assessment and meticulous monitoring of antivenom purity at the preclinical setting is hence crucial. This study aimed to explore an integrative proteomic method to assess the physicochemical purity of four commercially available antivenoms

Immunoassays are used for routine potency assessment of several vaccines, in some cases having been specifically developed as alternatives to in vivo potency tests. These methods require at least one well characterised monoclonal antibody (mAb) that is specific for the target antigen. In this paper we report the results of the comprehensive characterisation of a panel of mAbs against diphtheria with

FGF21 (Fibroblast Growth Factor 21), which is expressed in the liver, adipose tissue, and pancreas, has been widely known as a therapeutic candidate for metabolic diseases. Though FGF21 is crucial to glucose, lipid, and energy homeostasis, it is not straightforward to develop a new drug with FGF21 due to its short half-life in serum. Here, we derived a novel long-acting FGF21 (LAPS-FGF21), which is

Distressing effects on animal and human health with lethal progression, being used as bioweapon and shared features with non-pathogenic bacteria demands sensitive, specific, safe, cost effective and rapid detection methods for anthrax causing organisms. Conventional microbiology based diagnostics for anthrax are time consuming and need sophisticated equipment, while molecular diagnostics require less

To ensure the quality of raw materials for pharmaceutical products, the right storage and distribution temperature conditions should be applied. Labeled temperature conditions of 539 raw materials at non-cold chain conditions (thus excluding 2–8 °C or < 0 °C conditions) were reviewed that revealed a set of 26 different temperature requirements. From a manufacturer perspective, it is hard or undoable

Potency of meningococcal polysaccharide-protein conjugate vaccines relies on the polysaccharide content to prevent meningitis. NIBSC, as the official national control laboratory in UK, analysed ten different mono- and multi-meningococcal conjugate vaccines, using established International Standards for meningococcal serogroups A, C, W, Y and X, by resorcinol or HPAEC-PAD assay. Most saccharide contents

Rabies is a zoonotic disease that can be prevented by vaccination. The confirmation of rabies virus inactivation is a critical step during the vaccine quality test; however, the current protocol conducted in Japan requires a large number of mice. The development and introduction of animal-free alternative assays are essential from the perspective of the 3Rs (reduction, refinement, and replacement)

Viral contamination is a major concern for biological products. Therefore, virus testing of raw materials and cells is essential for the safety of the final product. We used high-throughput sequencing to detect viral-like sequences in selected CHO cell lines. Our aim was to test various approaches of sample preparation, to establish a pipeline for metagenomic analysis and to characterize standard viral

Tremendous progress has been made in recent years to produce functional cells for cell therapy products. Hundreds of clinical trials of stem cell products (SCPs) have shown promising therapeutic potential worldwide, including the products derived from human pluripotent stem cells (hPSCs), adult stem cells and mesenchymal stem cells (MSC). Before starting a clinical trial, comprehensive chemistry, manufacturing

Human adipose tissue derived mesenchymal stem cells (hAD-MSCS) with suppressive immunogenicity, homing to injury, inflammatory, and cancer sites can be suitable for gene therapy. PiggyBac (PB) is a type of transposon vector applied in mammalian systems and could overcome some limitations of other transposon and viral vectors. In this study, the therapeutic potential hAD-MSCs expressing thrombospondin-1

Replacement of the potency tests for diphtheria vaccines is a high priority for the international initiative to reduce, refine, and replace animal use in vaccine testing. Diphtheria toxoid containing vaccine products marketed in the US currently require potency testing by the United States Public Health Service (USPHS) test, which includes an in vivo passive protection test with a diphtheria toxin

Helicobacter pylori CagA protein plays an important role in the severity of the gastric diseases. Our aims were to clone the cagA 5′- conserved region of the gene, characterize the recombinant CagA (rCagA) protein by monoclonal antibodies (mAbs) and to use this protein for the detection of anti-CagA antibodies by an ELISA test. Our developed rCagA protein (67 kDa) showed an amino acid sequence homology

In Japan, the practical application of completely cell-based seasonal influenza vaccines is under consideration. Considering the good correlation between the immunogenicity of egg-based influenza vaccines and the hemagglutinin (HA) content determined by the single radial immunodiffusion (SRD) assay, we determined the potency of the first cell-based quadrivalent vaccine experimentally generated in Japan

Markers associated to NK cytolytic activity are in a great need to regulate NK cell immunotherapy products. We assume that biomarkers which response to cytolysis will change their transcription, expression or secretion. To find NK-92 indicator to cytolytic activity, we have evaluated the potential markers by quantifying the expression of well-known cytotoxicity functional molecules (cytokine IFN-γ

Transition to in vitro alternative methods from in vivo in vaccine release testing and characterization, the implementation of the consistency approach, and a drive towards international harmonization of regulatory requirements are most pressing needs in the field of vaccines. It is critical for global vaccine community to work together to secure effective progress towards animal welfare and to ensure

This International Alliance for Biological Standardization COVID-19 webinar was organized to provide an update on the virology, epidemiology and immunology of, and the vaccine development for SARS-CoV-2, none months after COVID-19 was declared a public health emergency of international concern. It brought together a broad range of international stakeholders, including academia, regulators, funders

Mesenchymal stromal cells (MSCs, also known as mesenchymal stem cells) are considered to be promising candidates for cell-based therapy of numerous skin disorders and wound healing. It is believed that MSCs differentiation into epithelial cells fill the area of the wound, while secretion of paracrine factors regulates cell homeostasis and adaptation. MSCs have been found to accelerate wound healing

Antibodies have strong affinity to their target molecules, a characteristic that is utilized in antibody drugs. For antibody drugs, target molecule specificity and long duration pharmacokinetics, along with strong affinity to the target molecule are important characteristics. Plasminogen activator inhibitor-1 (PAI-1) is one of the key regulators of the fibrinolysis system, and the benefits of PAI-1

Leningrad-Zagreb strain of mumps vaccine virus was grown on two different cell substrates viz. MRC-5 cells and Vero cells besides its original cell substrate i.e. Chicken Embryo Cells. Homogeneous virus pools prepared from each set of experiments were then lyophilized as per standard in-house protocol. Critical Quality Attributes (CQAs) such as the titer of the bulk vaccine and potency and stability

Hemin is one of the critical components of medium required for growth of Haemophilus influenzae type b (Hib) organisms. It is important to have different sources of critical components to ensure continuous supply for commercial production. Regulatory bodies also recommend having multiple sources for critical components. Hemin is produced from animal blood and the main sources are porcine and bovine

Current bacterial endotoxin testing systems can be labor-intensive and time-consuming, involving several manual pipetting steps. In our quality control laboratory, annually, we test about 15,000 samples of different grades of purified water, WFI and water samples taken to validate cleaning procedures for endotoxins. We are currently using the Kinetic-QCL™ assay which is a pharmacopeia method that provides

Heparin is an anticoagulant sourced from animal tissues. In the 1990s, bovine-sourced heparin was withdrawn from the U.S. market due to a theoretical concern that the bovine spongiform encephalopathy (BSE) agent might contaminate crude heparin and spread to humans as variant Creutzfeldt-Jakob disease. Only porcine intestinal heparin is now marketed in the U.S. FDA has encouraged the reintroduction

During vaccine production, RNA from chimeric yellow fever-dengue (CYD) vaccine viruses (CYD1, CYD2, CYD3 and CYD4) is currently quantified using separate serotype-specific RT-qPCR assays. Here we describe the results from a proof-of-concept study on the development of a multiplex reverse transcriptase droplet digital PCR (RT-ddPCR) assay for simultaneous quantification of RNA for all four viruses.

This second International Alliance for Biological Standardization COVID-19 webinar brought together a broad range of international stakeholders, including academia, regulators, funders and industry, with a considerable participation from low- and middle-income countries, to discuss the use of controlled human infection models to accelerate development and market authorization assessment of a vaccines

Effective decontamination procedures are critical to the successful manufacture and control of poliovirus vaccines to minimize the risk to personnel and the environment. Polio viruses have been reported to be more resistant to disinfectants than many other viruses. We assessed the efficacy of sodium hypochlorite-containing disinfectants for decontamination for three poliovirus serotypes to implement

The muscle-relaxing effects of the botulinum neurotoxin (BoNT) serotypes A and B are widely used in clinical and aesthetic medicine. The standard method for measuring the biological activity of pharmaceutical BoNT products is a mouse bioassay. In line with the European Directive 2010/63/EU, a replacement by an animal-free method would be desirable. Whereas the existing approved in vitro methods for

In recent years, several modified recombinant factor (F) VIII and FIX therapeutics with extended half-life have been licensed internationally for the treatment of haemophilia. Safe and effective use of these products requires monitoring of factor activity in patient plasma. The potency of all FVIII and FIX products is currently assigned in International Units (IU) which anchors the relationship between

New world Coral snakes comprise 82 species of medical importance distributed from southeastern United States to Argentina. In Colombia, Micrurus mipartitus and M. dumerilii are responsible for most coral snakebite accidents. Although infrequent, the severity of these envenomings, as well as the limited information available on the neutralizing coverage of commercially available antivenoms, underscores

Influenza is an acute respiratory infection caused by the influenza virus, and vaccination against influenza is considered the best way to prevent the onset and spread. MDCK (Madin-Darby canine kidney) cells are typically used to isolate the influenza virus, however, their high tumorigenicity is the main controversy in the production of influenza vaccines. Here, MDCK-C09 and MDCK-C35 monoclonal cell

Most antivenoms are produced by techniques developed over 50 years ago, with minor modifications. Herein we revise the core of traditional antivenom production processes aiming to optimize key determinants for both consistent antivenom production and the best balance between F(ab')2 quality and recovery. Factorial design analysis revealed that pepsin digestion of 1:3 saline diluted equine plasma for