Immunisation with UB-312 in the Thy1SNCA mouse prevents motor performance deficits and oligomeric α-synuclein accumulation in the brain and gut

Alpha synuclein has a key role in the pathogenesis of Parkinson’s disease (PD), Dementia with Lewy Bodies (LBD) and Multiple System Atrophy (MSA). Immunotherapies aiming at neutralising toxic αSyn species are being investigated in the clinic as potential disease modifying therapies for PD and other synucleinopathies. In this study, the effects of active immunisation against αSyn with the UB-312 vaccine were investigated in the Thy1SNCA/15 mouse model of PD. Young transgenic and wild-type mice received an immunisation regimen over a period of 6 weeks, then observed for an additional 9 weeks. Behavioural assessment was conducted before immunisation and at 15 weeks after the first dose. UB-312 immunisation prevented the development of motor impairment in the wire test and challenging beam test, which was associated with reduced levels of αSyn oligomers in the cerebral cortex, hippocampus and striatum of Thy1SNCA/15 mice. UB-312 immunotherapy resulted in a significant reduction of theαSyn load in the colon, accompanied by a reduction in enteric glial cell reactivity in the colonic ganglia. Our results demonstrate that immunisation with UB-312 prevents functional deficits and both central and peripheral pathology in Thy1SNCA/15 mice.

A point-of-care lateral flow assay for neutralising antibodies against SARS-CoV-2

As vaccines against SARS-CoV-2 are now being rolled out, a better understanding of immunity to the virus; whether through infection, or passive or active immunisation, and the durability of this protection is required. This will benefit from the ability to measure SARS-CoV-2 immunity, ideally with rapid turnaround and without the need for laboratory-based testing. Current rapid point-of-care (POC) tests measure antibodies (Ab) against the SARS-CoV-2 virus, however, these tests provide no information on whether the antibodies can neutralise virus infectivity and are potentially protective, especially against newly emerging variants of the virus. Neutralising Antibodies (NAb) are emerging as a strong correlate of protection, but most current NAb assays require many hours or days, samples of venous blood, and access to laboratory facilities, which is especially problematic in resource-limited settings. We have developed a lateral flow POC test that can measure levels of RBD-ACE2 neutralising antibodies from whole blood, with a result that can be determined by eye (semi-quantitative) or on a small instrument (quantitative), and results show high correlation with microneutralisation assays. This assay also provides a measure of total anti-RBD antibody, thereby providing evidence of exposure to SARS-CoV-2, regardless of whether NAb are present in the sample. By testing samples from immunised macaques, we demonstrate that this test is equally applicable for use with animal samples, and we show that this assay is readily adaptable to test for immunity to newly emerging SARS-CoV-2 variants. Accordingly, the COVID-19 NAb-testTM test described here can provide a rapid readout of immunity to SARS-CoV-2 at the point of care.

DEVELOPMENT AND PRODUCTION OF INFECTIOUS BURSAL DISEASE (GUMBORO) VACCINE IN NIGERIA

An infectious bursal disease virus strain obtained from an pathogenic strain that was attenuated in em-bryonated eggs, is produced in a primary culture of chicken embryo fibroblast, (CEF). This virus has been passaged 10 times further in CEF, and is now intended for use in the active immunisation of chickens against IBD. The vaccinę virus replicates well in CEF giving a titer of up to107.5 TCID50 per ml. In spite of its pathogenicity for CEF, the vaccine has no pathogenicity for chickens as shown by the absence of gross and histopathological lesions in the bursa of Fabricius (BF) of birds infected with it. Immunogenicity is retained and infact compares favourably with those of other IBD virus strains. The vaccine virus does not revert back to its original pathogenicity but can be adversely affected by storage at room temperature and at 37°C. It could however be stored at +2°C to +8°C or lower for up to six months without loss in potency, The vaccine can be administered by mouth or intramuscularly and as low as 50 TCID50 per bird guarantees full protection. However, as much as 125,000 times the guaranteed dose per bird has been administered without any observable changes in the BF of the affected birds. The field dosage is calculated so that at least one guaranteed dose (i.e. 50 TCID50 ) is still available to each bird even after incubation at 37°C for 7 days. The vaccine did not depress the immune response of chickens to ND vaccine intraocular when administered concurrently with it. The vaccine was tested for safety and immunogenicity in a population of two isolated flocks totalling 8504 birds. The immune status of a flock tested was significantly enhanced as a result of the vaccination (Table 6). More than 10.8 million doses have been issued to the field from 1979 to 1982 and the demand is increasing. Every batch of vaccine produced is tested for viability in CEF, sterility in bacterial culture media and for safety and potency in chickens.

Licorice: A Potential Herb in Overcoming SARS-CoV-2 Infections

The management of the global pandemic outbreak due to the coronavirus disease (COVID-19) has been challenging with no exact dedicated treatment nor established vaccines at the beginning of the pandemic. Nonetheless, the situation seems to be better controlled with the recent COVID-19 vaccines roll-out globally as active immunisation to prevent COVID-19. The extensive usage and trials done in recent outbreak in China has shown the effectiveness of traditional Chinese Medicines (TCM) in improving the wellbeing of COVID-19 patients. Therefore, COVID-19 Prevention and Treatment guidelines has listed a number of recommended concoctions meant for COVID-19 patients. Licorice, more commonly known as Gancao in Chinese Pinyin, is known as one of the most frequently used ingredients in TCM prescriptions for treatment of epidemic diseases. Interestingly, it is deemed as food ingredient as well, where it is normally used in Western cuisines’ desserts and sweets. The surprising fact that licorice appeared in the top 10 main ingredients used in TCM prescriptions in COVID-19 has drawn great attention from researchers in revealing its biological potential in overcoming this disease. To date, there are no comprehensive review on licorice and its benefits when used in COVID-19. Thus, in this current review, the possible benefits, mechanism of actions, safety and limitations of licorice were explored in hope to provide a quick reference guide for its preclinical and clinical experimental set-up in this very critical moment of pandemic.

Adenovirus Expressing the Myostatin-Somatostatin-fusing Gene Increases Mouse Growth Rate

Background Myostatin (MSTN), a type of transforming growth factor, can negatively regulate skeletal muscle growth. Immunisation of mice with recombinant yeast expressing MSTN increased bodyweight and muscle composition of them. Somatostatin (SST) is an inhibitory effector of growth hormone (GH), and active immunisation against SST with a DNA vaccine improves the growth performance of piglets via an influence on GH secretion. Here, a recombinant adenovirus was constructed and used to deliver MSTN-SST to mice to achieve the goal of regulation the growth performance of the mice. Results A recombinant adenovirus, rAd-MSTN-SST, expressing the MSTN-SST fusing protein was successfully rescued in HEK293A cells. The expressions of MSTN-SST were confirmed by western blotting and indirect immunofluorescence. Mice immunised with rAd-MSTN-SST were successfully induced to have an immune response against MSTN-SST, which increased their growth rate and muscle mass. In addition, a booster immunisation was beneficial in terms of higher antibody response and mouse growth rate. Conclusions Fusing protein MSTN-SST is a good candidate for regulating animal growth rate and muscle mass. Adenovirus can be used as a vector for delivering MSTN and SST to animals.

Adenovirus Expressing the Myostatin-Somatostatin-fusing Gene Increases Mouse Growth Rate

Background Myostatin (MSTN), a type of transforming growth factor, can negatively regulate skeletal muscle growth. Immunisation of mice with recombinant yeast expressing MSTN increased bodyweight and muscle composition of them. Somatostatin (SST) is an inhibitory effector of growth hormone (GH), and active immunisation against SST with a DNA vaccine improves the growth performance of piglets via an influence on GH secretion. Here, a recombinant adenovirus was constructed and used to deliver MSTN-SST to mice to achieve the goal of regulation the growth performance of the mice. Results A recombinant adenovirus, rAd-MSTN-SST, expressing the MSTN-SST fusing protein was successfully rescued in HEK293A cells. The expressions of MSTN-SST were confirmed by western blotting and indirect immunofluorescence. Mice immunised with rAd-MSTN-SST were successfully induced to have an immune response against MSTN-SST, which increased their growth rate and muscle mass. In addition, a booster immunisation was beneficial in terms of higher antibody response and mouse growth rate. Conclusions Fusing protein MSTN-SST is a good candidate for regulating animal growth rate and muscle mass. Adenovirus can be used as a vector for delivering MSTN and SST to animals.

Adenovirus Expressing the Myostatin-Somatostatin-fusing Gene Increases Mouse Growth Rate

Background Myostatin (MSTN), a type of transforming growth factor, can negatively regulate skeletal muscle growth. Immunisation of mice with recombinant yeast expressing MSTN increased bodyweight and muscle composition of them. Somatostatin (SST) is an inhibitory effector of growth hormone (GH), and active immunisation against SST with a DNA vaccine improves the growth performance of piglets via an influence on GH secretion. Here, a recombinant adenovirus was constructed and used to deliver MSTN-SST to mice to achieve the goal of regulation the growth performance of the mice. Results A recombinant adenovirus, rAd-MSTN-SST, expressing the MSTN-SST fusing protein was successfully rescued in HEK293A cells. The expressions of MSTN-SST were confirmed by western blotting and indirect immunofluorescence. Mice immunised with rAd-MSTN-SST were successfully induced to have an immune response against MSTN-SST, which increased their growth rate and muscle mass. In addition, a booster immunisation was beneficial in terms of higher antibody response and mouse growth rate. Conclusions Fusing protein MSTN-SST is a good candidate for regulating animal growth rate and muscle mass. Adenovirus can be used as a vector for delivering MSTN and SST to animals.

Adenovirus Expressing the Myostatin-Somatostatin-fusing Gene Increases Mouse Growth Rate

BackgroundMyostatin (MSTN), a type of transforming growth factor, can negatively regulate skeletal muscle growth. Immunisation of mice with recombinant yeast expressing MSTN increased bodyweight and muscle composition of them. Somatostatin (SST) is an inhibitory effector of growth hormone (GH), and active immunisation against SST with a DNA vaccine improves the growth performance of piglets via an influence on GH secretion. Here, a recombinant adenovirus was constructed and used to deliver MSTN-SST to mice to achieve the goal of regulation the growth performance of the mice. ResultsA recombinant adenovirus, rAd-MSTN-SST, expressing the MSTN-SST fusing protein was successfully rescued in HEK293A cells. The expressions of MSTN-SST were confirmed by western blotting and indirect immunofluorescence. Mice immunised with rAd-MSTN-SST were successfully induced to have an immune response against MSTN-SST, which increased their growth rate and muscle mass. In addition, a booster immunisation was beneficial in terms of higher antibody response and mouse growth rate. ConclusionsFusing protein MSTN-SST is a good candidate for regulating animal growth rate and muscle mass. Adenovirus can be used as a vector for delivering MSTN and SST to animals.