Maintains Outperform Rating
Monday, October 31, 2022
Inactivated SARS-CoV-2 and spike mRNA vaccines trigger different T-cell responses
The total magnitude of the T-cell responses induced by mRNA and inactivated SARS-CoV-2 vaccines are comparable; however, the similarity ends here, according to a new study led by Duke-NUS Medical School scientists.
They found that the inactivated vaccines, which expose the immune system to the entire non-viable virus, elicit a broad immune response against different proteins on the virus. Publishing in Cell Reports Medicine, the findings add to the growing literature that will help scientists improve vaccine strategies for an ever-changing virus.
"Inactivated SARS-CoV-2 vaccines were used extensively in Asia, but are often considered inferior due to their induction of a lower antibody response compared to other types of vaccines," said Dr. Anthony Tanoto Tan, Senior Research Fellow with the Duke-NUS' Emerging Infectious Diseases (EID) Program and a senior co-author of the study. "This means that they might not have been as good at preventing infection, but several studies have shown that they are highly capable of thwarting the development of severe COVID-19."
The research team compared the T-cell immune response in blood samples from people who received inactivated SARS-CoV-2 and spike mRNA vaccines. While mRNA vaccines can only induce T cells targeting SARS-CoV-2's spike protein, which contains numerous mutations in the omicron variant, the inactivated vaccines stimulated a broad T-cell response not only against the virus's spike protein, but also the membrane and nucleoprotein that has much fewer mutations in omicron.
"This combination of membrane, nucleoprotein and spike-specific T-cell response is quantitatively comparable to the sole spike T-cell response induced by the mRNA vaccine. It also effectively tolerates the mutations characterizing the omicron lineage," said Ms. Joey Lim Ming Er, first author of the study and a second-year student Ph.D. with the Integrated Biology and Medicine Ph.D. track at Duke-NUS.
However, unlike the mRNA vaccines, the inactivated virus vaccines did not appear to trigger cytotoxic CD8 T cells known for their ability to kill virus-infected cells. They mainly stimulated a type of T cells called CD4 T helper cells. When these T cells recognize a viral antigen, they release chemicals, called cytokines that helps the activation other types of immune cells, hence their name.
Senior author of the study Professor Antonio Bertoletti from Duke-NUS' EID Program said, "The omicron variant can effectively evade antibody neutralization, moving the evaluation of vaccination efficacy away from preventing infection and towards ameliorating disease. T cells are likely to play a more important role in this compared to antibodies, due to their ability to target virus-infected cells.
"Since inactivated SARS-CoV-2 vaccines can generate T cell responses towards other viral proteins, this more heterogenous response could be beneficial, in comparison to the current Spike targeting strategy of other vaccines. However, larger studies are needed to clarify the impact of these T cells responses in SARS-CoV-2 pathogenesis to better design vaccines for controlling severe COVID-19 after infection by omicron or future variants."
To dig deeper into the implications of the different T-cell responses, the scientists called for further research with larger numbers of participants, to compare the ability of the multi-protein CD4 T cell response induced by inactivated virus vaccines with that of the single spike protein coordinated CD4 and CD8 T cell response induced by mRNA vaccines to ameliorate COVID-19 disease severity.
More information: Joey Ming Er Lim et al, A comparative characterization of SARS-CoV-2-specific T cells induced by mRNA or inactive virus COVID-19 vaccines, Cell Reports Medicine (2022). DOI: 10.1016/j.xcrm.2022.100793
Anti-inflammatory molecules that decline in the aging brain
Aging involves complicated plot twists and a large cast of characters: inflammation, stress, metabolism changes, and many others. Now, a team of Salk Institute and UC San Diego scientists reveal another factor implicated in the aging process—a class of lipids called SGDGs (3-sulfogalactosyl diacylglycerols) that decline in the brain with age and may have anti-inflammatory effects.
The research, published in Nature Chemical Biology on October 20, 2022, helps unravel the molecular basis of brain aging, reveals new mechanisms underlying age-related neurological diseases, and offers future opportunities for therapeutic intervention.
"These SGDGs clearly play an important role in aging, and this finding opens up the possibility that there are other critical aging pathways we've been missing," says co-corresponding author Alan Saghatelian, professor in Salk's Clayton Foundation Laboratories for Peptide Biology and holder of the Dr. Frederik Paulsen Chair. "This is a pretty clear case of something that should be dug into more in the future."
SGDGs are a class of lipids, also called fats. Lipids contribute to the structure, development, and function of healthy brains, while badly regulated lipids are linked to aging and diseased brains. However, lipids, unlike genes and proteins, are not well understood and have often been overlooked in aging research. Saghatelian specializes in discovering new lipids and determining their structures.
His lab, in collaboration with Professor Dionicio Siegel at UC San Diego, made three discoveries involving SGDGs: In the brain, lipid levels are very different in older mice than in younger mice; all SGDG family members and related lipids change significantly with age; and SGDGs may be regulated by processes that are known to regulate aging.
To reach these findings, the team took an unusual, exploratory approach that combined the large-scale study of lipids (lipidomics) with structural chemistry and advanced data analytics. They first obtained lipid profiles of mouse brains at five ages, ranging from one to 18 months, using liquid chromatography-mass spectrometry.
Technological advances in this instrumentation vastly expanded the number of data points available to the scientists, and advanced data analysis allowed them to determine age-related patterns in the enormous lipid profiles. The team then constructed SGDG molecules and tested them for biological activity.
"SGDGs were first identified in the 1970s, but there were few follow-up studies. These lipids were essentially forgotten and missing from the lipid databases. Nobody knew SGDGs would be changing or regulated in aging, let alone that they have bioactivity and, possibly, be therapeutically targetable," says first author Dan Tan, a postdoctoral fellow in Saghatelian's lab at Salk.
The analysis showed that SGDGs possess anti-inflammatory properties, which could have implications for neurodegenerative disorders and other neurological conditions that involve increased inflammation in the brain.
The team also discovered that SGDGs exist in human and primate brains, suggesting that SGDGs may play an important role in animals other than mice. Further research will be required to show if SGDGs contribute to human neuroinflammation.
In the future, the team will examine how SGDGs are regulated with aging and what proteins are responsible for making them and breaking them down, which may open the door to discovering novel genetic activity associated with aging.
"With the understanding of the structure of SGDGs and our ability to create them in the laboratory, the study of these important lipids is now wide open and ripe for discovery," says Siegel, co-corresponding author of the study.
More information: Dan Tan et al, A class of anti-inflammatory lipids decrease with aging in the central nervous system, Nature Chemical Biology (2022). DOI: 10.1038/s41589-022-01165-6
Best blood thinner for minimizing bleeding risk
A large-scale comparison of direct oral anticoagulants (blood thinners), commonly prescribed for irregular heartbeats, has identified the drug associated with the lowest risk of bleeding, in a new study led by UCL researchers.
In the paper published in Annals of Internal Medicine, the researchers report that one of the two most common direct oral anticoagulants (DOACs), apixaban, offers the lowest risk of gastrointestinal bleeding, with similar performance on stroke prevention and other side effects.
DOACs are used to prevent strokes for people with atrial fibrillation—slow or irregular heartbeats—a condition affecting over 33 million people worldwide. They have recently become more common than warfarin, the previous standard treatment, as they do not require as much follow-up monitoring (which was particularly valuable during the COVID-19 pandemic) and carry less risk of side effects.
For the new study, the researchers compared the efficacy and risk of side effects for the four most common DOACs. They reviewed data from more than 500,000 new DOAC users in the UK, France, Germany and the US, including 281,320 apixaban users, 61,008 dabigatran users,12,722 edoxaban users, and 172,176 rivaroxaban users.
They found that all four drugs were comparable on outcomes for ischemic stroke, brain bleeds and all-cause mortality, while they did identify a difference in risk of gastrointestinal bleeding, which is one of the most common and concerning side effects of DOACs.
The study revealed that apixaban stood out as having lower risk of gastrointestinal bleeding, with 19-28% lower risks when compared directly to each of the other three DOACs.
The researchers found that their findings held true when looking at data only from those aged over 80, and those with chronic kidney disease, two groups that are often underrepresented in clinical trials.
Co-lead author Dr. Wallis Lau (UCL School of Pharmacy) said, "Direct oral anticoagulants have been prescribed with increasing frequency worldwide in recent years, but evidence comparing them directly has been limited. Our results indicate that apixaban may be preferable to other blood thinners because of the lower rate of gastrointestinal bleeding and similar rates of stroke, a finding that we hope will be supported by randomized controlled trials.
"As with all medications, potential risks and benefits can differ between people, so considering the full spectrum of outcomes and side effects will still be necessary for each individual patient."
Explore further
More information: Comparative Effectiveness and Safety Between Apixaban, Dabigatran, Edoxaban, and Rivaroxaban Among Patients With Atrial Fibrillation, Annals of Internal Medicine (2022). DOI: 10.7326/M22-0511
Invitae: therapy informed by genetic testing reduces seizures in some patients with epilepsy
Invitae (NYSE: NVTA), a leading medical genetics company, today announced the findings of a study that documents the actions clinicians take upon receiving a positive diagnostic genetic testing result for patients with epilepsy. The findings, in JAMA Neurology, demonstrate that a positive genetic diagnosis leads to clinical management changes in approximately half of patients and that changes implemented by clinicians based on genetic testing improve health outcomes in as many as three quarters of patients. When a change in management is made based on the results of a positive genetic test result, outcomes for patients with epilepsy generally improve, including reduction, and even complete elimination of seizures.
This study addresses a longstanding gap in understanding clinician action once positive genetic results are found for patients with epilepsy. A definitive molecular diagnosis obtained from epilepsy genetic testing led to important changes in clinical management that ultimately improved outcomes for patients. These changes included initiating medication, adding a new medication, or stopping a medication, and were made for half of the patients in the study within three months of testing. For patients with treatment changes, 75% were reported to have positive health outcomes including 65% who had reduction in seizure frequency and in some cases elimination of seizures.
Sweeping New Rules Will Curtail Student Loan Interest And Expand Loan Forgiveness Programs
The Biden administration has released final regulations that will provide sweeping changes to the federal student loan system. The new rules will curtail interest accrual and expand relief under several existing student loan forgiveness programs.
The release of these final regulations is the next step in a long process that began last year with negotiated rulemaking, where the Education Department convened key stakeholders to review and approve proposed reforms to student loan programs.
“Today is a monumental step forward in the Biden-Harris team’s efforts to fix a broken student loan system and build one that’s simpler, fairer, and more accountable to borrowers,” said U.S. Secretary of Education Miguel Cardona in a statement on Monday.
Here’s an overview of the major changes that will result from the new regulations.
Student Loan Interest Capitalization Reforms
The new federal regulations will curtail student loan interest capitalization.
In many circumstances, student loan interest can accrue on top of a borrower’s monthly payments, such as when the borrower is in an income-driven repayment plan. In addition, interest can accrue during many periods of nonpayment, such as a forbearance. Over time, this interest accrual can result in steadily increasing balances.
Adding to the problem is that certain events can cause that accruing interest to be added back on to the loan principal balance through a process called interest “capitalization.” Since interest is charged as a percentage of the loan principal, capitalization has a compounding effect, where interest accrues on interest. This can lead to substantial balance increases.
The new federal regulations will eliminate certain interest capitalization events including when a borrower first enters repayment, when a borrower exits a forbearance, and when a borrower leaves most income-driven repayment (IDR) plans such as Pay As You Earn (PAYE) and Revised Pay As You Earn (REPAYE). Interest will still be capitalized for borrowers who leave the Income-Based Repayment (IBR) plan, however, because changing that rule would require an act of Congress.
Expanded Student Loan Forgiveness
The final regulations released on Monday will also streamline and expand student loan forgiveness under several existing programs:
- For Borrower Defense to Repayment — a loan forgiveness program for borrowers misled or defrauded by their school — the new rules will strengthen protections for borrowers and expand the avenues of relief. The rules will allow the Education Department to provide individual or group relief, and will expand the categories of school misconduct that can give rise to a borrower claim. Borrowers will also be entitled to full relief (rather than partial relief, which had previously been permitted) for approved Borrower Defense claims.
- Borrowers will be entitled to automatic Closed-School Discharges “one year after a college’s closure date for borrowers who were enrolled at the time of closure, or [if they] left 180 days before closure and... do not accept an approved teach-out agreement or a continuation of the program at another location of the school.”
- Borrowers seeking loan forgiveness through the Total and Permanent Disability (TPD) discharge program will have an easier process of proving that they are disabled under the TPD standard. A greater percentage of borrowers receiving Social Security benefits will be entitled to relief automatically, and borrowers will no longer be subject to post-discharge income monitoring.
Additional Student Loan Relief Is Coming
The new federal regulations are expected to be effective by July 1, 2023. In the meantime, there are several other initiatives by the Biden administration that may provide significant relief for federal student loan borrowers by then, as well:
- The Limited PSLF Waiver, which temporarily relaxes key requirements associated with Public Service Loan Forgiveness, ends today. Millions of borrowers have already been approved. But there’s still time to apply.
- The Biden administration is in the process of developing a new Income-Driven Repayment (IDR) plan, which may be more affordable than current options and will also suspend excess interest accrual during periods where monthly payments do not cover all accruing interest.
- The Education Department is starting to roll out the IDR Account Adjustment initiative, which will provide retroactive credit towards borrowers’ 20-year and 25-year IDR student loan forgiveness terms, bringing millions of borrowers closer to eventual loan forgiveness.
- The administration is still accepting applications for its one-time student loan forgiveness initiative of $10,000 or $20,000. A federal appeals court has temporarily blocked the plan, but the Education Department is still encouraging borrowers to submit a student loan forgiveness application.
Glucose monitoring device maker DexCom stock rallies more than 50% in October to pace the S&P 500
DexCom eased today but stayed on track to be the S&P 500's best October performer with a month-to-date gain of 50.6%. The rally comes as maker of glucose monitoring systems reported last week third-quarter results that beat expectations and got a boost from the Centers for Medicare and Medicaid Services' issuing a proposal that would expand the coverage of glucose monitoring devices.
Subscribe to:
Posts (Atom)