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COVID vaccines: combining AstraZeneca and Pfizer may boost immunity – new study

A study at the University of Oxford has looked at what happens when people receive one dose of AstraZeneca one dose of Pfizer.

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Late last year, I asked: is it safe to have more than one type of COVID-19 vaccine? A trial has now addressed that question, as well as what effect combining different vaccine types has on immunity.

Most COVID-19 vaccines require two doses, and the usual strategy is to give people the same vaccine type for both. But the Com-Cov study, led by the University of Oxford, recruited over 800 participants from across the UK to investigate the effects of giving people different vaccines for their first and second jabs. Two vaccines were studied: those made by Pfizer and AstraZeneca.

So, is mix and match an option? The trial’s results are preliminary, having yet to be reviewed by other scientists, but the answer appears to be yes. Giving people different types of COVID-19 vaccine appears not only to be safe, but also a potential way of boosting protection against the coronavirus.

However, the exact benefits depend on which vaccine goes first and which second. Taking the AstraZeneca vaccine followed by the Pfizer one resulted in a striking increase in antibodies against the coronavirus’s spike protein (a key part of its outer structure) compared to using the AstraZeneca vaccine for both doses or Pfizer followed by AstraZeneca.


Read more: New coronavirus variant: what is the spike protein and why are mutations on it important?


Taking the AstraZeneca vaccine followed by Pfizer resulted in a better T cell response than all other combinations of doses. T cells – also known as T lymphocytes – are immune cells that help kill invading germs (such as the coronavirus) and support antibody production.

The Com-Cov study will next look at whether mixing and matching doses like this provides as good results when a larger gap is left between doses. The time between doses in this initial trial was 28 days, but a parallel study is stretching this to 84 days. The results are yet to be reported.

An expected outcome?

Other researchers have also been studying mixing vaccine types to fight COVID-19. A Spanish study recently reported that people who initially received the AstraZeneca vaccine experienced a massive increase to their antiviral immunity when given a second dose of the Pfizer vaccine – providing more evidence that Pfizer works well as a booster.

The body may mount an immune response against vaccines themselves – particularly those that use adenoviruses for delivery. Christoph Burgstedt/Shutterstock

To understand why these beneficial effects might be happening, it’s important to understand how the AstraZeneca and Pfizer vaccines work. Both present a key element of the coronavirus – again, the spike protein – to the immune system, but do so using different methods.


Read more: How the leading coronavirus vaccines work


The Pfizer approach packs the genetic code for the coronavirus’s spike protein into fatty nanoparticles. When these particles enter the body’s cells, the code is read and copies of the spike protein are produced, leading to an immune response. The AstraZeneca vaccine delivers the same genetic code but uses a weakened form of a common cold virus (an adenovirus) from chimpanzees to carry the code into cells.

When the first vaccine doses are given, it is possible that an immune response is raised not just against the spike protein created, but also against the carriers that are used to deliver the code for it. This is a known issue for treatments or vaccines that use viruses for delivery. If the second dose is then the same, the immunity developed against the carrier will react against the second dose, clearing some of it before robust, protective and long-lasting immunity develops.

This is why Russia’s Sputnik V vaccine – which is based on the same delivery method as the AstraZeneca vaccine – uses two different adenoviruses as carriers for its first and second doses, and has achieved impressive results.

Why mixing doses is so important

There are additional benefits to mixing vaccine doses on top of improving protection. Logistical problems can arise when a second vaccine dose has to be identical to the first. Producing double the quantity of one vaccine takes time. Boosting with a different vaccine could allow the world’s population to be vaccinated quicker.

Vials of COVID vaccines from AstraZeneca, Moderna, Pfizer and Johnson & Johnson
Next we need to see what happens when mixing COVID-19 vaccines from other manufacturers. Miguel Toro/Shutterstock

Second, if a person reacts badly to their first vaccination, they are more likely to get a second dose if they know it is a different one – and it’s clear that two are needed for good protection. Governments may also decide a certain type of vaccine is less suitable for different groups of people, as has been the case with the AstraZeneca vaccine in younger people in some countries. Having more potential vaccine combinations available may help overcome any public uncertainty in the wake of these sorts of decisions.

Supplying vaccines to some low- and middle-income countries can also be difficult, particularly if they do not have the necessary cold storage requirements for large batches of a vaccine that need to be kept at low temperatures. Including vaccines into the distribution plan that do not need storage at very low temperatures may make widespread vaccine delivery easier.

So there are clearly huge benefits to vaccine mixing. However, this study only looked at two vaccine types – in time, every combination will need to be tested, in every age group and in every ethnicity. Vaccines may also behave differently if mixed in different contexts, for example, against a backdrop of malnutrition or other infectious diseases. These factors will need to be included in future testing too. But for now, this study suggests that a mix-and-match approach to COVID-19 vaccines is an acceptable, useful option.

Tracy Hussell does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

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NYC biotech LB Pharmaceuticals eyes $75M for new take on decades-old schizophrenia drug

As Karuna Therapeutics wraps up its FDA approval request for what could be the first new type of schizophrenia drug in decades, another East Coast biotech…

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As Karuna Therapeutics wraps up its FDA approval request for what could be the first new type of schizophrenia drug in decades, another East Coast biotech is raising $75 million to test an adjusted version of a decades-old medicine for the disorder next year.

LB Pharmaceuticals has secured about $35 million so far and expects another $40 million in the round, according to an SEC filing on Thursday. Per the financial document, its board includes directors associated with Vida Ventures, Pontifax, Deep Track Capital and TCGX, a crossover firm that has invested in multiple nine-figure biotech financings in recent months, including Carmot Therapeutics, Alkeus and Upstream Bio.

LB declined to comment.

The New York City biotech plans to run a Phase II trial of a chemically differentiated form of amisulpride, a D2 and D3 antagonist that has been available in Europe and more than 50 countries for decades, according to an investor deck from June. Sanofi marketed it as Solian, which generated €135 million in sales in 2002 for the French Big Pharma. It’s since become available as a generic.

LB’s board includes Piero Poli, CEO of Swiss drugmaker Rivopharm, which produces generic amisulpride. In February 2020, Acacia Pharma secured FDA approval for an IV formulation of amisulpride in certain postoperative patients with nausea, marketing it as Barhemsys.

With its methylated version of amisulpride, LB says its oral asset LB-102 has the potential to be more effective at lower doses by improving blood-brain barrier permeability, per the investor deck. Its new chemical structure gives LB-102 IP protection until “at least 2037.” LB has positioned the drug as a blockbuster treatment that could generate $1 billion or more in annual sales, pointing to antipsychotic prescriptions in the EU with an average price of $2,000 per month.

The drug is set to go into Phase II testing in adults with acute schizophrenia in the first quarter of next year, per the June document.

The company expects to enroll about 350 people at 25 sites, testing whether three doses of the drug are better than placebo based on the commonly used schizophrenia clinical trial measure known as PANSS, or Positive and Negative Syndrome Scale. Karuna’s M1/M4-preferring muscarinic agonist KarXT has passed two Phase III trials that use that measure, leading to massive financing hauls for the biotech and Cerevel Therapeutics. Boston-based Karuna plans to submit its approval request to the FDA this quarter. Meanwhile, Sumitomo and Otsuka’s ulotaront failed a Phase III on the PANSS test two months ago.

LB expects the study to focus on in-patients for four weeks. Pending the mid-stage results, the company would likely then take LB-102 into multiple Phase III trials in 2025, with plans to submit an NDA in 2028, per the June presentation. The company sees schizophrenia as the first step, with potential for studies in depression, bipolar depression and other indications.

Zachary Prensky

The drug developer is led by a former family office manager, CEO Zachary Prensky. LB’s medical chief is Anna Eramo, who previously ran clinical and medical affairs at Lundbeck’s US operations and worked on the development of Rexulti, approved for schizophrenia and other indications. Science chief Andrew Vaino and chief financial officer Marc Panoff were previous executives at Retrophin.

Prensky co-founded LB with Vincent Grattan, a pharmacist who came across amisulpride in the 2000s while working on medication managements in multiple prisons. “As many are aware, correctional facilities are de facto mental health hospitals, and I wanted to make sure we were stocking the most reliable medications,” he told Psychiatric News in 2021.

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Dana-Farber, Brigham breakup could lead to a ripple effect for CGT clinical trials for cancer

Dana-Farber Cancer Institute announced on Sept. 14 that it is securing a new joint venture with Beth Israel Deaconess Medical Center, marking a breakup…

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Dana-Farber Cancer Institute announced on Sept. 14 that it is securing a new joint venture with Beth Israel Deaconess Medical Center, marking a breakup of its decadeslong adult cancer care partnership with Brigham and Women’s Hospital.

The news shocked Brigham, which had been negotiating a partnership extension with Dana-Farber for the past 15 months, according to the Boston Globe.

There are around 20 ongoing cell therapy clinical trials under the Dana-Farber Brigham Cancer Center, which comprises 12 treatment centers with experts from Dana-Farber and Brigham working together. Brigham also has its own gene and cell therapy institute and a lab dedicated to next-generation, genetically-modified CAR-T cell therapies for cancer.

With the Dana-Farber contract set to end in 2028, concerns have been raised about the impact on current cell and gene therapy (CGT) studies and ones that are scheduled to start, due to the complex nature of the treatments involved.

Jason Foster

Manufacturing CGTs is a skill- and labor-intensive process. Ori Biotech CEO Jason Foster told Endpoints News that hospitals and research centers often work together to make them on-site for clinical trials, with highly skilled experts from the specialty centers playing a key role. UK-based Ori develops technologies that automates CGT manufacturing.

At Dana-Farber Brigham Cancer Center’s cellular therapies program, cells are processed at an outside commercial facility or at the Connell and O’Reilly Families Cell Manipulation Core Facility.

When such partnerships come to an end, “that kind of [specialist] knowledge loss is something that will impact both the trajectory of [CGT] trials, but also the time it takes to get these products to patients,” Foster added.

These potential negative impacts on trials would only compound preexisting barriers to access to CGTs, including high costs and lengthy manufacturing processes. Estimates suggest that 25% of patients die while waiting for CAR-T treatments, according to ASCO Post.

Lee Buckler

Lee Buckler, senior vice president of advanced therapies at Blood Centers of America, told Endpoints in an email that collaboration between research institutes and healthcare providers was of significant — if not critical — value to the testing of CGTs.

A Brigham spokesperson said that the hospital is one of the largest recipients of NIH funding and does not expect any changes to trials already under agreement, adding it would continue to be a leader in the CGT space. “We are also planning for a new, state of the art Brigham facility which will include the medical oncology specialty,” the spokesperson said.

Dana-Farber did not respond to Endpoints before deadline.

Problems with CGT trials could be both the cause and the effect of partnership breakdowns. Buckler said that general hospitals are often reluctant to facilitate the kinds of clinical trial protocols associated with innovative CGTs, which may drive research centers to align with partners more willing to prioritize them.

Under the new partnership with Beth Israel, Dana-Farber plans to create a free-standing state-of-the-art cancer hospital, which it said would have the flexibility to “incorporate the innovations and technology in cancer care that Dana-Farber’s and BIDMC’s researchers and clinicians are developing every day.”

Vered Caplan

But a dedicated cancer hospital is not necessarily better at carrying out CGT trials than a general hospital with a tightly-integrated cancer specialty.

“I’ve seen general hospitals with tremendous capabilities and specific hospitals with tremendous capabilities — it really depends on the particular hospital,” Orgenesis CEO Vered Caplan told Endpoints in an interview. Germantown, MD-headquartered Orgenesis rolls out CGT mobile processing units and labs for cancer treatment to hospitals.

Regardless, the breakup means Dana-Farber must convince patients that its program with Beth Israel will provide at least the same quality care as the Brigham partnership, while Brigham must rebuild its specialist capabilities without Dana-Farber expertise.

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Zelensky Departs Washington Mostly Empty-Handed Amid Mood Shift In West

Zelensky Departs Washington Mostly Empty-Handed Amid Mood Shift In West

By all accounts, Zelensky came away from his Washington visit with…

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Zelensky Departs Washington Mostly Empty-Handed Amid Mood Shift In West

By all accounts, Zelensky came away from his Washington visit with nothing new. Biden did announce a fresh $325 million aid package for Ukraine from already committed funds, but the hoped-for long range missile approval never came (however, more cluster bombs are being sent). And as we detailed Thursday, House Republican leadership once again failed to move forward on a mere procedural vote for the Pentagon funding bill, due in large part to GOP members rejecting Biden's proposed $24 billion more in Ukraine aid.

Thursday's package announced by Biden, as Zelensky visited the White House and Capitol Hill, was run-of-the-mill and entirely to be expected. "Today I approved the next tranche of U.S. security assistance to Ukraine including more artillery, more ammunition, more anti-tank weapons and next week, the first U.S. Abrams tanks will be delivered to Ukraine," Biden said.

As for the earlier in the day (Thurs.) meeting with Congressional leaders, House Speaker Kevin McCarthy explained when asked why the Ukrainian leader's request to address Congress was denied, "Zelensky asked for a joint session, we just didn't have time. He's already given a joint session."

Via AFP

Instead in a closed-door meeting, Zelensky later acknowledged he discussed with lawmakers "the battlefield situation and priority defense needs."

But if there is any level of consolation for Kiev, it's seen in the Pentagon announcement which came late in the day Thursday. Facing potential US government shutdown on Oct.1st, given at this point Congress is not expected to pass the 12 appropriations bills needed to fund government operations before next fiscal year, the Pentagon has said it will exempt its operations supporting Ukraine from a shutdown. 

The military typically suspends any activities not deemed vital to national security during government shutdowns, thus the DoD is in effect saying Ukraine aid remains "vital to national security". 

"Operation Atlantic Resolve is an excepted activity under a government lapse in appropriations," Pentagon spokesman Chris Sherwood told Politico, in reference to the operational name still used for actions supporting Kiev.

But Politico points out a potential shutdown would still negatively impact US support to Ukraine:

Sherwood noted that while DOD’s activities related to Ukraine will continue, furloughs and other activities halted under the shutdown could still have a negative impact.

"Training would happen, but depending on whether or not there were certain personnel that were not able to report for duty, for example, that could have an impact," said Pentagon spokesperson Brig. Gen. Patrick Ryder on Thursday.

This Pentagon exemption to keep Ukraine-related support active during a government shutdown seems to be the only significant thing Zelensky came away with. 

It appears to have been the main object of discussion when Zelensky met with Secretary of Defense Lloyd Austin in Washington during the trip. The Pentagon said this was "to reaffirm the steadfast US support for Ukraine."

Meanwhile, Bloomberg takes note of Zelensky "showing the strain" amid increasing divisions among allies:

The Ukrainian president allowed a dispute with one of his biggest allies to spin out of control at the United Nations General Assembly this week, and that’s just a hint of the tensions building behind the scenes.

Zelenskiy has been leading his country through Russia’s brutal assault for 19 months, all the time fighting on another front to wring the weapons and finance he needs from his US and European supporters. Now he suspects that President Joe Biden’s commitment is wavering and other leaders may be taking their cue from the US, according to a person who met with him recently.

He grew very emotional at times during that discussion, the person said, and was scathing in his criticism of nations that he said weren’t delivering weapons quickly enough.

Washington's lackluster greeting of Zelensky this week (compared to how he was received in December 2022) came simultaneous to Poland declaring it will no longer arm Ukraine, amid a fierce diplomatic spat over blockage of Ukraine grain imports by Warsaw, to protect Polish farmers.

The Economist is also taking note of the significant mood shift among Western allies...

A "long war" indeed... given a G7 leader from a European country has told reporters this week that the West is prepared for a years-long war, something likely to last some six or seven years, according to the quote.

"A senior official from one European G-7 country said the war may last as much as six or seven more years and that allies need to plan financially to continue support for Kyiv for such a long conflict," Bloomberg wrote.

Tyler Durden Fri, 09/22/2023 - 10:15

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