Tag: 22/4/21

New High-yield Vaccine Technology Recycles Cell Junk

As the world struggles with COVID vaccine production bottlenecks and scaling issues, a team from Northwestern University synthetic biologists have developed a high-yield vaccine technology, increasing production of protein-based vaccines by a factor of five.

Scaling up COVID vaccine production has proved extremely challenging. Adenovirus vaccines such as AstraZeneca’s need to be cultured in 2000 litre tanks containing human cells and then extracted, while mRNA vaccines like that produced by Pfizer requires very careful mixing, as well as components and only a few companies have the skills to produce them. The promising protein subunit vaccines such as Novavax’s offering may be easier to scale up, but also require specific adjuvant, which uses saponin from the bark of a Chilean tree, Quillaja saponaria, which is also used in other vaccines.

Earlier this year, the researchers introduced a new biomanufacturing platform that can quickly make shelf-stable vaccines at the point of care, ensuring they will not go to waste due to transportation or storage problems. In this new study, the team found that enriching cell-free extracts with cellular membranes—the components needed to made conjugate vaccines—massively boosted yields of its freeze-dried platform.

The new technology can produce 40 000 doses per litre per day of antibiotics or vaccines, costing about $1 per dose. At that rate, the team could use a 1000 litre reactor to generate 40 million doses per day, reaching 1 billion doses in less than a month.

“Certainly, in the time of COVID-19, we have all realized how important it is to be able to make medicines when and where we need them,” said study leader Michael Jewett, a professor of chemical and biological engineering at Northwestern. “This work will transform how vaccines are made, including for bio-readiness and pandemic response.”

The new manufacturing platform—called in vitro conjugate vaccine expression (iVAX)—is made possible by cell-free synthetic biology, a process where a cell’s outer wall (or membrane) is removed, and its internal machinery repurposed. This repurposed machinery is then placed in a test tube and freeze-dry it. The cell-free system is activated by the addition of water, turning it into a catalyst for making usable medicine when and where it’s needed. With a shelf-life of over six months, the platform eliminates the need for complicated supply chains and extreme refrigeration, making it extremely valuable for remote or low-resource settings.

In a prior study, Jewett’s team used the iVAX platform to produce conjugate vaccines to protect against bacterial infections, repurposing molecular machinery from Escherichia coli to make a single dose of vaccine in an hour, at $5 per dose.

“It was still too expensive, and the yields were not high enough,” Prof Jewett said. “We set a goal to reach $1 per dose and reached that goal here. By increasing yields and lowering costs, we thought we might be able to facilitate greater access to lifesaving medicines.”

Prof Jewett and his team found that the cell’s membrane, which is typically discarded in cell-free synthetic biology, was key to solving this. When broken apart, membranes naturally reassemble into vesicles, spherical structures that still carry important molecular information. Studying these vesicles, the researchers discovered that increasing vesicle concentration could be useful in making components for protein therapeutics such as conjugate vaccines, which work by attaching a sugar unit—that is unique to a pathogen—to a carrier protein. 

Normally attaching the sugar unit to the protein is very complex, but the researchers found that the cell’s membrane contained machinery that enabled the sugar to more easily attach to the proteins. When they enriched vaccine extracts with this membrane-bound machinery, the researchers significantly boosted usable vaccine yields.

“For a variety of organisms, close to 30% of the genome is used to encode membrane proteins,” said study co-author Neha Kamat, who is an assistant professor of biomedical engineering at McCormick and an expert on cell membranes. “Membrane proteins are a really important part of life. By learning how to use membrane proteins effectively, we can really advance cell-free systems.”

Source: Phys.Org

Journal information: Improving cell-free glycoprotein synthesis by characterizing and enriching native membrane vesicles, Nature Communications (2021). DOI: 10.1038/s41467-021-22329-3

People Most in Need of PrEP Don’t Use It

Though sexual minority men and transgender women are aware of pre-exposure prophylaxis (PrEP), a daily pill to prevent HIV infection, few are currently taking it, a New York-based study has found.

The study, published in the journal AIDS and Behavior, surveyed 202 young sexual minority men and transgender women, who are two high-priority populations for HIV prevention, to better understand the factors in their taking PrEP or not.

According to the Centers for Disease Control and Prevention, sexual minority men are the community most impacted by HIV, making up 69% of all new diagnoses in 2018, and transgender populations are disproportionately affected by HIV and prevention challenges. While Black and Hispanic populations are mostly likely to be newly diagnosed with HIV, PrEP users are more likely to be white.

The research team, who is from the Rutgers School of Public Health’s Center for Health, Identity, Behavior and Prevention Studies (CHIBPS), found that while 98 percent of the study’s participants were aware of PrEP, less than 25 percent were currently taking it.

“It was surprising that so few participants were using PrEP, but we were happy to see that there were no racial or ethnic disparities in who was using it,” Caleb LoSchiavo, Study Co-Author and Doctoral Candidate, School of Public Health, Rutgers University. “I think the study results point to the effectiveness of local efforts to increase the use of PrEP for those who need it most.”

While the study PrEP found no differences in use use, it also found racial and ethnic differences in factors associated with taking it. White participants were more likely to use PrEP with increased age, and were less likely to use it if they held concerns about daily medication use. Participants of colour, however, were more likely to use PrEP if they received information about it from a health care provider and if they had more positive beliefs about its use.

“Our study highlights the importance of clinicians in expanding the use of HIV prevention methods like PrEP among those who need it most, both through informing their patients about PrEP and through combating stigmatizing beliefs about PrEP use,” said senior study author Perry N Halkitis, dean of the Rutgers School of Public Health and director of CHIBPS.

The researchers said that the study emphasised the importance of PrEP education in clinical settings.

“Positive public health messaging about PrEP must reframe risk, combat stigma and normalize preventive healthcare,” LoSchiavo said.

Source: News-Medical.Net

Journal information: Jaiswal, J., et al. (2021) Correlates of PrEP Uptake Among Young Sexual Minority Men and Transgender Women in New York City: The Need to Reframe “Risk” Messaging and Normalize Preventative Health. AIDS and Behavior. doi.org/10.1007/s10461-021-03254-4.

Stemming the Flow of the ‘Spice’ Drug

The ‘spice’ drug, which has dangerous side effects, is becoming more popular around the world, partly due to the difficulty in detecting its presence.

Spice is the street name for one type of synthetic cannabinoids (SC), which a heterogeneous group of compounds developed to probe the endogenous cannabinoid system or as potential therapeutics. Clandestine laboratories subsequently used published data to develop SC variations marketed as abusable ‘designer drugs’. In the early 2000’s, SC became popular as ‘legal highs’, partly due to their ability to escape detection by standard cannabinoid screening tests. While they provide a similar ‘high’ to cannabis, they are seen as safer but in fact they have serious and potentially fatal side effects.

In 2019, the team developed a prototype of their spice-detecting device and found it could detect the drug from saliva and street material in under five minutes. The current test involves lab analysis of urine, with results after three to seven days.

Dr Chris Pudney from the University’s Department of Biology & Biochemistry, and creator of the new technology, said faster testing is essential if users are to receive treatment and harm-reduction interventions.

“There is no way of knowing if spice has been taken if someone presents with psychosis or intoxication symptoms that could also be due to other reasons,” said Dr Pudney. “So we see the detection technology as a way to inform care in case of overdose.”

The test’s obvious advantages have resulted in great interest, resulting in a grant which the Bath research team will use to create a simple field-usable testing solution.

Dr Pudney said: “Spice is endemic in homeless communities and prisons. It’s highly potent, addictive and poses severe health risks to users including psychosis, stroke, epileptic seizures and can kill. We want to deliver a detection system both to raise the prospect of rapid treatment and to stem the flow of drugs in these communities.”

There are also recent reports of children ‘mistaking’ spice for cannabis, resulting in numerous hospital admissions.

“Drug testing and checking, which is increasing in many countries around the world and in the UK, has been shown to have an impact on drug-taking behaviour and to potentially reduce risk,” said Dr Jenny Scott from the University’s Department of Pharmacy & Pharmacology and who is also involved in the research.

“Spice use is a particular issue in homeless communities. In the future, we hope our technology can be used to offer drug testing to spice users and to tailor harm-reduction information to these vulnerable people. The machines could be used in drugs services, homeless hostels and further down the line, in pharmacies.”

The new spice-testing technology will be based on a cloud-hosted data analytics platform.

“We hope to combine this technology with a deeper understanding of the communities that use spice so that we can deploy the spice-detecting technology in the most effective way possible to benefit the most vulnerable in society,” said Dr Pudney. “Our ultimate aim is to save both money and lives.”

By the end of the grant period, the group aims to start a not-for-profit social enterprise to bring their technology to the mainstream. The group plans to roll out the full range of activities needed to deliver the technology, including portable device design, analytical software development, chemical fingerprint libraries and the associated community pharmacy practice advice to deploy the technology effectively.

“We believe the scope and potential of our research is truly unique and presents the best chance for tackling spice use in the UK and more widely,” said Dr Chris Pudney.

Source: News-Medical.Net

With Advanced ‘Vaporfly’ Shoes, Female Runners Close Gap with Males

Female and male runners in starting positions. Photo by Andrea Piacquadio from Pexels

A new paper found that Nike’s advanced ‘Vaporfly’ footwear reduced running times for both elite male and female competitors.

The introduction of the controversial Nike ‘Vaporfly’ shoes saw world records being broken and a marathon run in under two hours, prompting a review and subsequent ban on the high-tech shoes.

The study compared seasonal best times for elite male and female runners in three race categories—10 kilometres, half marathon and marathon races—from 2012 to 2019. Analysis showed a statistically significant decrease in race times after 2017, which coincided with the premiere of the Nike ‘Vaporfly’.

Female elite athletes appeared to gain the most benefit from the design improvement, which features a thicker, lighter foam and rigid plate along the midsole. Their seasonal best times between 2016 and 2019 fell anywhere from 1.7 to 2.3%, versus 0.6 to 1.5% for the men. In marathons, the new shoe technology improved times for females by about 2 minutes and 10 seconds, a 1.7% percent boost in performance.

“As far as chronometric performance is concerned, it is in our opinion a major advancement,” said lead author Dr Stéphane Bermon, director of the World Athletics Health and Science Department.

How the performance has been achieved is still mostly a mystery. The new shoe technology uses the latest generation of lightweight foam in the midsole, which provides the runner with a higher energy return. The embedded stiff plate in the midsole also contributes to maximising energy return in each step. The net effect is to propel the runner forward with greater ease.

The statistical gap between genders was unexpected, said Dr Bermon. One advantage could come down to weight between the sexes.

“Women are lighter and could possibly benefit more from the enhanced rebound effect achieved by the foam/stiff plate combination,” he said. “Their slightly different running pattern, compared to men, could represent a more favorable condition for this footwear technology to play its ergogenic role.”

A previous 2018 statistical analysis had already suggested a 3 to 4% decrease in half marathon and marathon race times based on hundreds of thousands of self-reported results. However, the present study was the first to compare the top seasonal best times for elite athletes.

While East African runners, like Ethiopian and Kenyan, make up the majority of the results as they have come to dominate the sport, the paper noted that non-East-African elite runners showed similar improvements in performance.

“These results confirm that advanced footwear technology has benefits to the elite male and female distance runners,” Dr Bermon said. “Whether this technology will be banned or simply controlled, as it is currently, is still to be decided by World Athletics.”

No immediate follow-up studies are planned, though Dr Bermon said additional research is needed into injury rates with the new footwear with mass adoption.

Source: Medical Xpress

Journal information: Stéphane Bermon et al, Effect of Advanced Shoe Technology on the Evolution of Road Race Times in Male and Female Elite Runners, Frontiers in Sports and Active Living (2021). DOI: 10.3389/fspor.2021.653173

A Golden Opportunity for Metformin as a Cancer Drug

In a new study from the National University of Singapore, a new approach to target highly resistant triple-negative breast cancers (TNBCs) has been developed using a gold-metformin prodrug.

Metformin, first approved by the FDA in 1994, is a widely prescribed “over-the-counter” medication for Type 2 diabetes. Some evidence shows that people taking metformin for an extended period have a significantly reduced cancer risk. In spite of evidence of its effects and its low cost, use of metformin as an anticancer agent has serious drawbacks, with poor uptake by cells necessitating repeated high doses to have a therapeutic effect.
A team of researchers led by Prof Ang Wee Han from the Department of Chemistry, National University of Singapore and Prof Maria Babak from City University of Hong Kong came up with a way of chemically conjugating metformin, as well as its analog phenformin. They accomplish this by using a gold-based active molecular fragment to increase bioavailability and achieve synergistic action of the two key components (metformin and gold molecules). 

The electrochemical activity of the gold-based molecule,enabled the team to successfully deliver metformin into cancer cells with high selectivity. The lead drug candidate, 3met, was found to have an anti-cancer activity over 6000 times higher than regular metformin.

Prof Ang said, “TNBCs represent an especially dangerous subset of breast cancers with the poorest prognosis and limited treatment options. However, this particular aggressiveness of TNBC cells is related to their increased dependence on glucose and lipids, which provide additional energy to sustain rapid cancer growth. Since our drug candidates interfered with energy production in the cancer cells, we hypothesized that TNBCs might be particularly responsive to such treatment.”

In tests with mice, the research team injected the drug candidate into breast tumours at their nipple region and monitored the growth of the tumours. They found that in a drug-treated group, tumour growth completely halted after three weeks, indicating the unique anticancer potential of the drug candidate. 

With an patent application filed for, the research team is actively working on the development of other efficient drugs for the treatment of chemo-resistant cancers.

Source: Medical Xpress

Journal information: Maria V. Babak et al. Interfering with Metabolic Profile of Triple‐Negative Breast Cancer using Rationally‐Designed Metformin Prodrugs, Angewandte Chemie International Edition (2021). DOI: 10.1002/anie.202102266

NICD Tracking Rise of COVID Cases

Following a steep rise in COVID cases in three provinces, The National Institute for Communicable Diseases (NICD) is working with teams in those areas to monitor the situation.

Increases in the Northern Cape, North West and Free State have been observed by the NICD. The Northern Cape has over 3000 active cases, the North West over 2600 and the Free State over 2200.

The NICD said that it was working with provinces to ascertain whether the rise in cases could be attributed to cluster outbreaks and has recommend increased testing and contact tracing to contain the situation.

Acting executive director of the NICD, Professor Adrian Puren, said: “We want to reassure South Africans that we are actively monitoring the situation in these provinces and will keep the community informed of any new developments.”

The NICD said that with the April school holiday season soon starting and many people making plans for travel and social gatherings, it was still vital to continue to comply with COVID preventative health measures.

Earlier this month, Discovery Health described possible scenarios for COVID in South Africa. Poor social distancing and masking behaviours, superspreader events and a lack of early vaccinations, a third wave could claim as many as 76 000 lives, the insurance company estimated. However, by maintaining good nonpharmaceutical interventions and engaging in a prompt vaccination rollout, deaths would fall to 9000 by the end of the year.

The NICD monitors the number of confirmed COVID-19 cases and tests performed on a daily basis and associated resurgence metrics.

Source: Eyewitness News