Existing COVID Vaccines Trigger Lasting T Cell Response

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Scientists have found that four COVID vaccines (Pfizer-BioNTech, Moderna, J&J/Janssen, and Novavax) prompt the body to make effective, long-lasting T cells against SARS-CoV-2. These T cells can recognise SARS-CoV-2 Variants of Concern, including Delta and Omicron.

The new study, published in Cell, showed that the vast majority of T cell responses are also still effective against Omicron, reducing the odds of illness for up to six months, regardless of vaccine.

These data come from adults who were fully vaccinated, but not yet boosted. The researchers are now investigating T cell responses in boosted individuals and people who have experienced “breakthrough” COVID cases.

The study also shows that fully vaccinated people have fewer memory B cells and neutralising antibodies against the Omicron variant. This finding is in line with initial reports of waning immunity from laboratories around the world.

Without enough neutralising antibodies, Omicron is more likely to cause a breakthrough infection, and fewer memory B cells means a slower production of more neutralising antibodies.

Co-first author Camila Coelho, PhD, said: “Our study revealed that the 15 mutations present in Omicron RBD can considerably reduce the binding capacity of memory B cells.”

Neutralising antibodies and memory B cells are only two arms of the body’s adaptive immune response. , T cells do not prevent infection, rather they patrol the body and destroy cells that are already infected, which prevents a virus from multiplying and causing severe disease.

The team believes the “second line of defence” from T cells helps explain Omicron’s reduced severity in vaccinated people. The variant also appears to infect different tissues.

To know whether the vaccine-induced T cells they detected in their study were actually effective against variants such as Delta and Omicron, the scientists took a close look at how the T cells responded to different viral “epitopes.”

Every virus is made up of proteins that form a certain shape or architecture. A viral epitope is a specific landmark on this architecture that T cells have been trained to recognise. Current COVID vaccines were designed to teach the immune system to recognise specific epitopes on the initial variant of SARS-CoV-2, specifically targeting the Spike protein which the virus uses to access human cells. As the virus has mutated, its architecture has changed, and the concern is that immune cells will no longer recognise their targets.

The new study shows that while the architecture of Omicron is different enough to evade some neutralising antibodies and memory B cells, memory T cells still do a good job of recognising their targets, even on the highly mutated Omicron variant. Overall, at least 83 percent of the CD4+ (helper) T cell responses and 85 percent of the CD8+ T cell responses stayed the same, no matter the vaccine or the variant.

The memory B cells that do bind Omicron are likely to also contribute to protection against severe disease, forming multiple lines of defence. 

Researchers are now focusing on measuring T cells, B cells and antibody responses after COVID booster shots, and also characterising immune responses after a breakthrough infection.

Source: La Jolla Institute

Two Key Proteins with a Major Role in Ageing

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In the largest genetic study of ageing to date, two key proteins have been identified that play a significant role in the ageing process. Developing drugs that target these proteins could be one way of slowing down ageing.

Genetics, lifestyle, environment and chance influence ageing. The study sheds light on the part proteins play in this process. Some people have higher or lower levels of certain proteins according to their individual DNA, which in turn affect a person’s health.

In a study published in Nature Aging, researchers from the University of Edinburgh combined the results of six large genetic studies into human ageing – each containing genetic information on hundreds of thousands of people.

Among 857 proteins studied, researchers identified two that had significant negative effects across various ageing measures.

People who inherited DNA that causes raised levels of these proteins were frailer, had poorer self-rated health and were less likely to live an exceptionally long life than those who did not.

The first protein, apolipoprotein(a) (LPA), is made in the liver and thought to play a role in clotting. High levels of LPA can increase the risk of atherosclerosis – a condition in which arteries become clogged with fatty substances. Heart disease and stroke is a possible outcome.

The second protein, vascular cell adhesion molecule 1 (VCAM1), is primarily found on the surfaces of endothelial cells lining blood vessels. The protein controls the vessels’ expansion and retraction – and have a function in blood clotting and the immune response.

Levels of VCAM1 increase in response to signals indicating an infection, and the protein then allows immune cells to cross the endothelial layer.

The researchers say that drugs used to treat diseases by reducing levels of LPA and VCAM1 could have the added benefit of improving quality and length of life.  

One such example is a clinical trial that is testing a drug to lower LPA as a way of reducing the risk of heart disease. No clinical trials with VCAM1 are underway, but studies in mice have shown how antibodies lowering this protein’s level improved cognition during old age.

The identification of these two key proteins could help extend the healthy years of life. Drugs that reduce these protein levels in the blood could allow the average person to live as healthy and as long as individuals who have won the genetic lottery and are born with genetically low LPA and VCAM1 levels.

Source: University of Edinburgh

Muscles may Stay Younger at an Epigenetic Level through Exercise

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While the benefits of exercise in ageing have been well established, such as lowering risk of cardiovascular disease, a new study that used mice demonstrated that exercise in aged individuals could help muscles stay younger at an epigenetic level.

Despite generating a wealth of data, the study, which was published in Aging Cell, made use of a relatively straightforward experiment. Lab mice nearing the end of their natural lifespan, at 22 months, were allowed access to a weighted exercise wheel. Mice generally run voluntarily, without any coercion. Older mice will run anywhere from six to eight kilometres a day, mostly in spurts, while younger mice may run up to 10 to 12 kilometres. The weighted wheel ensured they built muscle. While there isn’t a direct analogue to most human exercise routines, first author Kevin Murach, assistant professor at the University of Arkansas, likened it to “a soldier carrying a heavy backpack many miles.”

When the mice were examined after two months of progressive weighted wheel running, it was determined that they were the epigenetic age of mice eight weeks younger than sedentary mice of the same age – 24 months. Murach noted that while the specific strain of mice and their housing conditions can impact lifespans, “historically, they start dropping off after 24 months at a significant rate.” Needless to say, when your lifespan is measured in months, an extra eight weeks – roughly 10 percent of that lifespan – is a noteworthy gain.

The science behind this hinges largely on DNA methylation, where methyl groups attach to DNA, altering their function. As the body ages, there tends to be increased DNA methylation, or even hypermethylation, at promoter sites on genes in muscle. “DNA methylation changes in a lifespan tend to happen in a somewhat systematic fashion,” Murach explained, “to the point you can look at someone’s DNA from a given tissue sample and with a fair degree of accuracy predict their chronological age.” Due to this, researchers can use one of a number of “methylation clocks” to determine the age of a DNA sample.

While the paper strengthens the case for exercise, much work remains to be done. Though there is a clear connection between methylation and ageing, the relationship between methylation and muscle function is less clear. Murach is not yet prepared to say that the reversal of methylation with exercise causes improved muscle health. “That’s not what the study was set up to do,” he explained. However, he intends to pursue future studies to determine if “changes in methylation result in altered muscle function.”

Source: University of Arkansas

A New Method to Block Listeria Infections

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University of Queensland researchers have unlocked a way of fighting Listeria infections, which can cause severe and potentially illness in pregnant women and immunocompromised individuals.

Listeria infection does not cause disease in most people, but can be deadly for the immunocompromised and is also a major health concern during pregnancy and can lead to miscarriage, stillbirth and premature birth.

From 2017 to 2018, South Africa suffered the world’s largest listeriosis outbreak, in which there were 216 deaths out of 1060 recorded cases.

During the study, published in the journal PLOS Pathogensresearchers discovered a way to block Listeria from making the proteins that allow bacteria to survive and multiply in immune cells. University of Queensland’s Professor Antje Blumenthal said using a small, drug-like inhibitor has improved their understanding of Listeria’s weak spot.

Listeria is found in the soil and sometimes in raw foods. Once ingested it can hide from the immune system and multiply inside immune cells,” Prof Blumenthal said.

“Instead of killing the bacteria, the immune cells are used by the bacteria to multiply and are often killed by Listeria growing inside them.

“Our study showed the bacteria could be cleared with a small drug-like inhibitor that targets the ‘master regulator’ of the proteins that help Listeria grow in immune cells. The inhibitor helped the immune cells survive infection and kill the bacteria.”

Previously, studies into Listeria’s ‘master regulator’, which controls critical proteins that make the bacteria virulent, have mostly been based on engineered bacteria, or mutated versions of these proteins.

“By using a drug-like inhibitor, we were able to use molecular imaging and infections studies to better understand what happens to Listeria when the bacteria cannot effectively grow inside immune cells and hide from immune defence mechanisms,” Prof Blumenthal said.

“We hope that our discovery, together with recent research into the master proteins’ molecular structure and functions, could guide the development of inhibitors and new drugs to treat Listeria infection.”

“Our findings could also inform design of inhibitors against related proteins that are found in different bacteria,” Prof Blumenthal said.

Source: University of Queensland

Simple Dietary Supplement in Type 1 Diabetes Calms Immune System

Gut microbiome. Credit: Darryl Leja, NIH

A clinical trial performed by Australian scientists showed that a simple dietary supplement that targeted gut microbiota could improve gut health and strengthen the immune system in individuals with type 1 diabetes.

The supplement is a type 2–resistant starch consisting of a high-amylose (70%) maize starch that has been modified by bonding the acetate and butyrate. The supplement is resistant to digestion in the upper gastrointestinal tract and delivers a very high yield of short-chain fatty acids (SCFAs) in the colon. This makes it a useful tool to measure the effect of SCFAs on intestinal biology.

According to senior author and lead investigator Dr Eliana Marino, the study tested 21 adults with type 1 diabetes who incorporated the supplement into their daily diet for six weeks. Increased production of metabolites by the gut microbiota was observed, specifically SCFAs. This has an important role in preventing type 1 diabetes.

“People with 1 diabetes have shown altered gut microbiota and reduced production of short-chain fatty acids in stools and blood. We previously have demonstrated that the supplement used in this human study protected mice from diabetes,” said Dr Marino.

Published in Microbiome, the clinical trial showed that participants’ blood immune cells developed a more regulatory phenotype post-intervention.
“We were very excited to find that blood immune cells had become more regulated. Because type 1 diabetes is caused when the immune system becomes too activated and attacks the insulin-producing cells in the pancreas,” said co-lead researcher Associate Professor Hamilton-Williams.

“Type 1 diabetes is a lifelong autoimmune disease that is on the rise with no cure. Individuals living with type 1 diabetes depend on insulin treatment. As a consequence, they can develop late life-threatening inflammatory complications, such as kidney failure, neurological and cardiovascular diseases,” said co-lead researcher Associate Professor Sonia Saad

“While glucose control and insulin requirements didn’t change overall, the participants with the highest short-chain fatty acid concentrations showed the best glucose control after the supplementation,” said co-lead researcher Dr Kirstine Bell.

“Using this supplement for longer and starting it earlier in the disease could potentially stop the immune attack, preserving insulin-producing cells and improving glucose regulation,” said Dr Marino.

“This dietary supplementation represents a safe and accessible alternative therapy for many children with type 1 diabetes or other autoimmune diseases. Also, it could decrease the risk of subsequent inflammatory complications such as cardiovascular disease as clinical trials are underway,” said Dr Marino.

Source: Monash University

A New Test to Diagnose Dizziness without Deafening

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Swedish researchers have developed a new way to diagnose dizziness problems in a simpler and less painful way than the old method. A bone conduction speaker, easily attached behind the ear, can make the diagnosis more efficient and safer – especially for patients with pre-existing hearing problems.

For patients with dizziness, the relationship of dizziness and hearing is used for diagnosis. Typically, a ‘VEMP’ test (Vestibular Evoked Myogenic Potentials) is performed. With loud sounds, the test evokes a muscle reflex contraction in the neck and eye muscles, triggered by the vestibular system. In their new approach, reported in Communications Medicine, researchers at Chalmers University instead made use of bone-conducted sounds to achieve better results.

“We have developed a new type of vibrating device called B250 that is placed behind the ear of the patient during the test,” said Bo Håkansson, a professor at Chalmers University. “The vibrating device is small and compact in size and optimised to provide an adequate sound level for triggering the reflex at frequencies as low as 250 Hz, which we have found to be optimal for VEMP stimulation. Previously, no vibrating device has been available that was directly adapted for this type of test of the balance system.”

In bone conduction transmission, sound waves are transformed into vibrations through the skull, stimulating the cochlea within the ear, in the same way as when sound waves normally go through the ear canal, the eardrum and the middle ear. This can be used in various technologies such as in hearing aids.

Half of over-65s suffer from dizziness, but the causes can be difficult to diagnose for several reasons. Dizziness in 50% of those cases results from vestibular system problems. But current VEMP methods have major shortcomings and can cause hearing loss and discomfort for patients. The VEMP test uses very high sound levels which can cause permanent hearing damage. Additionally, if certain types of hearing loss are already present, the test can be inconclusive.

“The previous test was like a machine gun going off next to the ear – with this bone-conduction method it will be much more comfortable. The sound levels to which patients are exposed can be minimised. The test can be performed at 40 decibels lower than today’s method, which uses air-conducted sounds through headphones. This eliminates the risk that the test itself could cause hearing damage,” said researcher Karl-Johan Fredén Jansson, who made all the measurements in the project.

“The benefits also include safer testing for children, and that patients with impaired hearing function due to chronic ear infections or congenital malformations in the ear canal and middle ear can still be diagnosed for the origin of their dizziness,” said Prof Håkansson.

The device has now been tested and developed in several patient studies that have been published internationally, both with healthy individuals to obtain normal data, and in patients suffering from various types of dizziness. The device is compatible with standardised equipment for balance diagnostics in healthcare, which makes it easy to use. In addition to the benefits for patients, the cost of the new technology is also judged to be lower than the corresponding equipment used today.

Source: News-Medical.Net

Medical Bodies Push Back against Commission for Gender Equality’s Statement

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The South African Medical Research Council (SAMRC), along with other professional medical and scientific institutions released a statement  distancing themselves from the Commission for Gender Equality’s (CGE) press release of 16 January, 2022, titled “Warning Against Imposing Mandatory Covid-19 Vaccination on Employees and Students”. [PDF]

The CGE cited an article published in Obstetrics and Gynaecology which found that women receiving Pfizer-BioNTech, Moderna or J&J COVID vaccines, vaccine administration was associated with less than a one-day change in cycle length for both vaccine-dose cycles compared with pre-vaccine cycles. The article concluded that clinically meaningful change in menstrual cycle duration associated with COVID vaccination was found. 

The CGE used this study as justification, cautioning businesses and institutions against mandatory vaccination and recommended against sanctions for employees who chose to remain vaccinated.

The signatories expressed their concern at the contents of the statement which is at odds with the scientific understanding of COVID vaccinations, a concern which is compounded by the “enormous influence” of the GCE.

They accept that the vaccine mandates are subject to legal scrutiny, but take issue with the commission “trying to bolster its argument by wrongly insinuating that COVID vaccination has the potential to harm women’s health.”

They also point out that the commission seems to disregard the much greater risks to women and their unborn babies of COVID infection, while misinterpreting evidence on minor menstrual cycle lengthening. This creates fear and confusion in vaccinated women, and may increase vaccine hesitancy.

“It fails to appreciate that one in six unvaccinated pregnant women admitted to hospital in South Africa with COVID infection requires mechanical ventilation, and one in 16 has a fatal outcome,” the signatories stated.

They noted that COVID vaccination provides upwards of 80% protection against severe disease, hospitalisation and death.

They endorse the view of the College of Obstetricians and Gynaecologists of South Africa, which draws on research of the highest quality, that the menstrual effects are minor.

The evidence is “indisputable” that COVID vaccination is safe, does not negatively affect women’s bodies and saves the lives of women, they stress. Statements to the contrary are strongly repudiated.

“We are of the view that the CGE, like all state institutions, medical and scientific bodies, social partners and civil society formations working in the fields of women’s rights, empowerment and equality, should urge women to get vaccinated and advance and defend their rights to all relevant information about and access to vaccination.”

The signatories call on the CGE to withdraw its 16 January statement and to share with it scientific facts on COVID vaccination and women’s health.

Source: South African Medical Research Council

How Many Intervention Sessions to Prevent Cognitive Decline?

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Physical activity, diet and cognitive stimulation are all known to be good interventions for the prevention of Alzheimer’s disease and dementia. Now an international team of researchers has determined that only about a dozen intervention sessions are all that were needed to observe an improvement in cognition.

Until now, the number of sessions or “doses” needed for optimal effect has been unknown. Published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, the study led by Université de Montréal psychology professor Sylvie Belleville showed that between 12 and 14 sessions were all that were needed to boost cognitive ability, though the gain observed levelled off with more sessions.

“In pharmacological studies, every effort is made to define an optimal treatment dose needed to observe the expected effects, “ said Prof Belleville,  a neuropsychologist and researcher at the research centre of the UdeM-affiliated Institut universitaire de gériatrie de Montréal. “This is rarely done in non-pharmacological studies, especially those on the prevention of cognitive decline, where little information is available to identify this dose.

“Defining an optimal number of treatment sessions is therefore crucial.,” she continued. “Indeed, proposing too few sessions will produce no noticeable improvement effects, but too many sessions is also undesirable as these interventions are costly. They are costly both for the individual who follows the treatments, in terms of time and involvement, and for the organisation offering these treatments.”

The study is based on a secondary analysis of data from the three-year Multidomain Alzheimer Preventive Trial (MAPT) and examined 749 participants who received a range of interventions aimed at preventing cognitive decline. These interventions included dietary advice, physical activity and cognitive stimulation.

In their research, Prof Belleville’s team noted that people’s individuality should be considered when determining the optimal treatment dose.

In their study, the researchers gauged the effects of the sessions in terms of each participant’s age, gender, education level, and cognitive and physical condition. The relationship between the “dose” each received and their cognitive improvement was then analysed.

The findings revealed an increase with dose followed by a plateau effect after 12 to 14 sessions. However, participants with lower levels of education or more risk factors for frailty did benefit from more sessions.

The researchers concluded that it’s important to pinpoint an optimal dose and to customise the treatment for each individual. Not only is “dosage” an important component of behavioural interventions, it can also provide valuable information in resource-constrained settings, helping public-health agencies develop effective prevention programs and offer guidance to older adults and clinicians.

Source: University of Montreal

SA Healthcare Bolstered With Vaccine Lab Investment and Loans

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Last week, South African healthcare received a double shot in the arm with the opening of a local vaccine manufacturing facility and the approval of a World Bank loan to bolster social safety nets and health systems.

On Wednesday, President Cyril Ramaphosa and health technology billionaire Dr Patrick Soon-Shiong officially opened a new vaccine manufacturing facility in Brackenfell, Western Cape.

The South African-born entrepreneur has been strongly supporting local healthcare, with R3 billion invested to help SA share vaccine technology with the rest of Africa. His company, ImmunityBio, is developing a T-cell based universal COVID vaccine, currently in Phase III trials in SA. The same adenovirus vector technology it uses is also being tested in cancer vaccines.

“It has been a dream of mine, since I left the country as a young physician, to bring state-of-the-art, 21st century medical care to SA and to enable the country to serve as a scientific hub for the continent,” Dr Shoon-Siong had previously said. The technology transfer will help “establish much-needed capacity and self-sufficiency.”

The hub will transfer technology, know-how and materials for DNA, RNA, adjuvant vaccine platforms and cell therapies to SA.

“There is no reason we couldn’t make 500 million doses a year,” said Dr Soon-Shiong, who is also a Wits alumnus. “Subject to the raw material being available.”

He said he wants to tap the country’s expertise on prevalent diseases such as HIV and cervical cancer. “There are fantastic scientists with deep knowledge about these diseases,” he said. “More so than in America because they see these patients every day.”

President Ramaphosa and Dr Soon-Shiong also launched the Coalition to Accelerate Africa’s Access to Advanced Healthcare, which aims to drive the development of innovative therapeutics and ensure the continent is prepared for future pandemics.

The coalition aims to manufacture a billion doses of the COVID vaccine by 2025 and to develop treatments for conditions including cancer, COVID, tuberculosis and HIV.

South Africa also received approval from the World Bank for a US$750 million COVID relief loan aimed at reducing the worst of the pandemic’s impact on the poor.

“The World Bank budget support is coming at a critical time for us and will contribute towards addressing the financing gap stemming from additional spending in response to the COVID crisis,” said Dondo Mogajane, Director General of the National Treasury. “It will assist in addressing the immediate challenge of financing critical health and social safety net programs whilst also continuing to develop our economic reform agenda to build back better.”

Meanwhile, Health Minister Dr Joe Phaahla warned that South Africa will likely enter a fifth wave when cold temperatures in May, though what COVID variants may drive it remain to be seen.

K-Wires for Wrist Fractures on Par with Cast

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Using metal K-wires (aka ‘pins’) to hold broken wrist bones in place while they heal are no better than a traditional moulded plaster cast, finds a study published by The BMJ.

If the bone fragments in wrist fractures have displaced, they often require manipulation followed either by surgery to insert metal wires or plates, or a moulded cast as a non-surgical alternative, to hold the bones in place while they heal.

Surgery is expensive and carries risk for the patient, whereas a moulded plaster cast is cheaper but may not provide the same functional outcome.

To see which option is superior, researchers tracked the progress of 500 adults, average age of 60 and 83% female. with a displaced wrist fracture. Patients were randomly allocated to receive a cast (255) or surgical fixation with K-wires (245) after manipulation of their fracture. The primary outcome measure was the Patient Rated Wrist Evaluation (PRWE) score at 12 months, which included questions about pain, function and disability, and gave an overall score from 0 (best) to 100 (worst).

Secondary outcomes were PRWE score at three and six months, quality of life, and complications, including the need for later surgery.

Of the 79% of patients who completed the follow-up, no statistically significant difference was seen in the PRWE score at three, six or 12 months (average score 21.2 in the cast group compared with 20.7 in the K-wire group). Quality of life was similar.

However, one in eight patients with cast needed later surgery for loss of fracture position in the first six weeks after their injury compared with only one patient in the K-wire group.

Other complications were rare, with no evidence of a difference between the two groups (28 in the cast group compared with 22 in the K-wire group).

Limitations included the fact that neither the treating clinicians nor the participants could be blind to the interventions. Still, the researchers noted this was a large trial involving adults of all ages and the results are based on validated patient reported outcomes, reflecting the care provided across a healthcare system.

As such, they conclude: “Surgical fixation with K-wires did not provide better wrist function at 12 months compared with a moulded cast, indicating that a cast is an acceptable first line treatment following manipulation of a dorsally displaced fracture of the distal radius.”

They added: “Cast treatment avoids the expense and risks of surgical fixation for seven out of eight patients. However, careful follow-up is needed as one in eight patients treated with a cast required subsequent surgical intervention as the fracture reduction could not be maintained.”

Source: The BMJ