New COVID-19 study quantifies antibody response to Pfizer, Moderna vaccines

 New research from the University of Virginia School of Medicine quantifies the antibody response generated by the Pfizer and Moderna COVID vaccines. The findings are some of the earliest to compare the two vaccines' antibody responses head-to-head. The notable finding was that antibody levels in recipients of the Moderna vaccine were slightly higher than in recipients of Pfizer. The difference was mostly accounted for by antibody levels in relatively older subjects.

The researchers caution against drawing conclusions about the vaccines' effectiveness based on the antibody numbers. Both vaccines, they say, have performed exceptionally after having been given to millions of people around the world. The new results are just a small piece in a much larger puzzle as scientists seek to determine if one vaccine may be superior for certain demographics.

"The thing that will be interesting is figuring out if measuring antibody levels ends up being a good marker of vaccine protection," said UVA immunologist Jeffrey Wilson, MD, Ph.D. "At the moment, we don't know for sure."

Pfizer and Moderna, head-to-head

The Pfizer and Moderna vaccines both use mRNA to teach the immune system how to defend itself against COVID's spike protein. However, the formulations for each vaccine are slightly different, with Moderna using more mRNA than Pfizer. That prompted the UVA scientists to seek to quantify and compare the resulting antibody responses.

To do that, they examined blood from 167 UVA employees who received the vaccines. The samples were collected one week to 31 days after the recipients' second vaccine dose. Although subjects were not randomly assigned in the study, the vaccine that was administered was dictated by local availability at the time of vaccination, with 79 receiving Pfizer and 88 receiving Moderna. In some cases, the researchers were able to obtain a blood sample prior to the second dose—either before or after the first dose.

The average age of study participants was 42, and 38% were 50 or older. Most—72%—were women.

Overall, the researchers found that Moderna produced more antibodies in the blood after the second dose than did Pfizer: 68.5 micrograms per milliliter (µg/mL) for Moderna versus 45.9 for Pfizer.

To explore the effect of age on antibody responses, the researchers stratified participants into those younger than 50 or 50 and older. Pfizer recipients age 50 and older produced fewer antibodies than younger recipients after the second dose (31.1 µg/mL vs. 59.0 µg/mL). This age disparity was not seen in people who received the Moderna vaccine. The researchers speculate that this is because of the difference in the amount of mRNA the vaccines contain—Moderna uses more than three times as much.

The scientists note that they did not specifically look at "neutralizing" antibodies—the type of antibodies that block the virus from entering cells. They also did not look at T cells and B cells, which are other vital players in the body's immune response. That will require more complex studies and more time.

"Ultimately, I think you need to do the hard studies. And the hard studies are looking at clinical outcomes and how they relate to antibody levels," Wilson said.

The new results are, however, an important data point as doctors and scientists map out the future response to the pandemic. Scientists continue to study the vaccines' long-term effectiveness and are assessing if booster shots will be needed, especially among older people who may not have generated as strong an immune response as younger ones.

In the meantime, Wilson endorsed both Pfizer and Moderna without hesitation for anyone who is not yet vaccinated. Both will vastly reduce the risk of serious illness or death. With infection numbers rising around the country, he had this advice: "Please, get your shot."

The researchers have published their findings in the scientific journal JAMA Network Open.

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Pfizer seeking FDA OK for COVID-19 vaccine booster dose

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More information: Nathan E. Richards et al, Comparison of SARS-CoV-2 Antibody Response by Age Among Recipients of the BNT162b2 vs the mRNA-1273 Vaccine, JAMA Network Open (2021). DOI: 10.1001/jamanetworkopen.2021.24331

https://medicalxpress.com/news/2021-09-covid-quantifies-antibody-response-pfizer.html

Japan confirms first cases of mu coronavirus variant

 Japan on Wednesday confirmed its first cases of the new mu variant of the coronavirus in two people arriving from abroad through airport screenings.

The health ministry announced that the mu variant was detected in a woman in her 40s who arrived on June 26 from the United Arab Emirates. The other case was with a woman in her 50s who arrived on July 5 from the U.K. Both women were asymptomatic upon arrival.

All travelers to Japan are required to take a PCR test upon arrival and wait for results — if they test positive, they are quarantined in a designated facility or hospitalized depending on their symptoms. Even if they test negative, they are required to quarantine for 14 days at home or a designated facility depending on where they have come from.

The ministry said it would continue to take measures to prevent the spread of the variant by closely monitoring the situation in other countries.

On Monday, the World Health Organization designated the mu variant, also known as B.1.621, as a variant of interest, the second-highest level in its classification of variants.

It remains unclear, however, how transmissible the mu variant is or whether it is resistant to vaccines.

But in a statement released Tuesday, the WHO warned that the variant “has a constellation of mutations that indicate potential properties of immune escape.” This means that vaccines or antibody treatments may not work as well against the mu strain as they do against the original version of the coronavirus.

In its weekly pandemic bulletin, the WHO added that preliminary data showed reduced effectiveness of vaccines against mu similar to that seen for the beta variant, which was discovered in South Africa and is considered to be more contagious than the original coronavirus.

At present, the WHO designates alpha, beta, gamma and delta as variants of concern, the highest classification.

The mu strain was first detected in Colombia in January and currently accounts for about 40% of cases in the country, according to the WHO. The mutation has so far been detected in at least 40 countries but makes up less than 0.1% of all cases worldwide, the organization said.

The WHO also said that since the variant was first identified, there have been a few sporadic reports of infections with the mu variant and even of some larger outbreaks in other countries in South America and in Europe.

The health ministry’s announcement follows a recent report about a new sublineage of the delta variant that emerged in Japan in mid-August. Delta, which originated in India, has become the most prevalent variant in Japan.

So far, the alpha, beta, delta, gamma, kappa, lambda and mu variants have been confirmed in Japan.

https://www.japantimes.co.jp/news/2021/09/02/national/japan-coronavirus-mu-variant/

MONOCLONAL ANTIBODIES FOR HIGH-RISK COVID-19 POSITIVE PATIENTS - HHS

 If you’ve tested positive for COVID-19, one of the first questions you may have is, What can I do to reduce the risk of getting sicker? The good news is, there are treatments that may reduce that risk. Depending on your age, health history, and how long you’ve had symptoms of COVID-19, you may qualify for a promising form of treatment for the disease. It’s called monoclonal antibody (mAb) treatment.

Some early evidence suggests that mAb treatment can reduce the amount of the SARS-CoV-2 virus (the virus that causes COVID-19) in a person's system. This amount is known as viral load. Having a lower viral load means you may have milder symptoms thereby decreasing the likelihood of you needing to stay in the hospital.

mAb treatment may help people who:

• Have a positive COVID-19 test, and had symptoms for 10 days or less
• Are at high risk of getting more serious symptoms

Visit the page How Do I Know If I’m High Risk, and What Do I Do Next? to learn more.

This page describes what mAbs are, how they can prevent mild to moderate symptoms from getting worse, and what to expect if you get mAb treatment.

Find infusion locations

Have symptoms, but no healthcare provider? Call the Combat COVID Monoclonal Antibodies Call Center at 1-877-332-6585.

https://combatcovid.hhs.gov/i-have-covid-19-now/monoclonal-antibodies-high-risk-covid-19-positive-patients

Over 80% In US Have Some Immunity To Coronavirus: Blood Survey

 More than 80% of Americans have some level of immunity against the coronavirus, mostly through vaccination, a survey of blood donations indicates.

The survey, led by the US Centers for Disease Control and Prevention, also indicates that about twice as many people have been infected with the virus as have been officially counted. More than 39 million Americans have been diagnosed with coronavirus infection since the pandemic started in 2020.

The team, led by the CDC’s Dr. Jefferson Jones, set out to determine how close the US might be to some kind of herd immunity — although they do not claim to have any kind of handle on that yet.

They worked with 17 blood collection organizations working in all 50 states plus Washington, DC, and Puerto Rico to test blood covering 74% of the population. In the end, they tested about 1.4 million samples.

In July 2020, before any vaccine was available, 3.5% of samples carried antibodies to SARS-CoV-2, the virus that causes Covid-19. That rose to 11.5% by December, they reported in the medical journal JAMA. By May, 83.3% of samples had antibodies to the virus, most of them from vaccination.

And while in July 2020, blood surveillance indicated the US was only counting one infection out of every three true infections, that fell to one in two a year later.

This was all pre-Delta, the researchers caution. Plus, they didn’t measure the other part of the human response — one involving cells known as T-cells — and one that might induce broader immunity. But knowing who has antibodies can help inform public health efforts.

“Several large studies have shown that among individuals who are seropositive from prior SARS-CoV-2 infection, COVID-19 incidence is reduced by 80% to 95%, similar to vaccine efficacy estimates,” they noted.

“The study will continue until at least December 2021, and results will be made available on the CDC’s website,” they wrote.

Covid-19 hospitalizations in the United States have been rising steadily since early July, but are starting to show signs of improvement, data from the US Department of Health and Human Services shows.

Total hospitalizations nearly tripled in July and doubled again in August, according to HHS data, and for the past eight Sundays, total hospitalizations were an average of 25% higher than the week before.

But over the past seven days, total hospitalizations in the US grew by only 2%. In fact, there were 134 fewer new admissions during the week of August 24 than there were during the previous week.

Together, Covid-19 hospitalizations in Florida and Texas account for nearly 30% of current hospitalizations across the country. Hospitalizations in Florida have declined 11% over the past week, and hospitalizations in Texas have steadied, contributing heavily to improvements in national trends.

But hospitalizations remain perilously high; there are currently 102,804 people hospitalized for Covid-19 in the United States, 72% of the way to the peak from mid-January, according to HHS data. Overall, hospitals across the country are nearly three-quarters full and ICUs are about 80% fully.

At least nine states have had record high hospitalizations in recent days, reaching peaks higher than any other point during the pandemic, including Georgia and Tennessee, where hospitalizations continue to rise. Most of these states have fully vaccinated a smaller share of their residents than the US overall. In Georgia and Tennessee, about 42% of the population is fully vaccinated, compared to about 53% of the US population overall, according to data from the US Centers for Disease Control and Prevention.

More than 500,000 children tested positive for Covid-19 in 3 weeks

More than 500,000 children tested positive for Covid-19 in the US from August 5 to August 26, according to state data collected by the American Academy of Pediatrics. At least 203,962 of those cases were reported in the week of August 19 to August 26; In late June, one weekly reported number was just shy of 8,500.

With concerns building over safely allowing children to return to in-person learning at schools, health experts agree that mask mandates are an effective tool in stemming infections.

“The virus is raging in all these children who are unvaccinated, which is why in schools mask mandates are so important,” CNN medical analyst Dr. Jonathan Reiner told Jake Tapper last week, pointing out that inoculation rates are also low among adolescents who are eligible. “They have no other protection. They’re literally sitting ducks.”

For teens ages 12 and up attending classes, it remains imperative for them to receive vaccinations to help curb the spread of Covid-19, officials say. And vaccine mandates, while unpopular to some, may be a necessary step.More states and school districts across the country are imposing mask and vaccine mandates, while others are working to limit Covid-19 exposure among the unvaccinated. New York Gov. Kathy Hochul announced on Tuesday plans to implement mandatory weekly Covid-19 testing for state school staff who are not vaccinated.

“We all need to remain vigilant to protect each other – and that means coming in to get your shot and booster shot, wearing masks in indoor spaces, and exercising basic safety measures that we are all familiar with by now,” Hochul said.

“I believe that mandating vaccines for children to appear in school is a good idea,” Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told CNN this week, noting that this would not be a radical idea to impose.

“This is not something new. We have mandates in many places in schools, particularly public schools, that if in fact you want a child to come in — we’ve done this for decades and decades requiring (vaccines for) polio, measles, mumps, rubella, hepatitis,” Fauci said. “So this would not be something new, requiring vaccinations for children to come to school.”

Officials expect additional vaccine data soon

Cognizant of the anxiousness felt by some parents and guardians sending their children back to school unvaccinated, health officials say they are working expediently to review whether the age of vaccine eligibility can be lowered.

If authorized, the CDC would move quickly to recommend the use of Covid-19 vaccines in younger children, agency director Dr. Rochelle Walensky said.

“Everybody is looking at this with urgency. Everyone recognizes how important it is for those children to have access to vaccines,” Walensky said during a National Parent Teacher Association town hall Wednesday.

The US Food and Drug Administration (FDA) must approve or authorize the vaccines in younger children first, Walensky noted. And the vaccine makers must make the case to the FDA with clinical trial data.

“My understanding of the timeline is pretty consistent with what is being said — the middle of fall is my understanding, early fall is when we will anticipate seeing the data — and then it will lie with the hands of the FDA. And I’m hopeful for the end of the year,” she said.

Pfizer/BioNTech’s vaccine has been fully approved by the FDA for Americans 16 and older, and emergency use authorization has been granted for those 12 and up. The Moderna and Johnson & Johnson vaccines are under emergency use authorization only for adults 18 and older.

Moderna announced last week that it had completed its submission to the FDA for full approval, and has also filed with the FDA for an emergency use authorization for its vaccine in people age 12 and older.

Clinical trials of vaccines for children under the age of 12 are ongoing.

Fauci said Wednesday that the FDA should have the data to consider authorizing a Covid-19 vaccine for children under 12 by the end of September.

“We should have enough of the data to examine and make a decision as we get into late September, the beginning of October,” Fauci said. “Then the data will be presented to the FDA, and the FDA will make a determination whether they will grant that under an emergency use authorization or some other mechanism.”

When asked whether a Covid-19 vaccine will be authorized for young children before Thanksgiving, Fauci said he hopes so, but does not want to get ahead of the FDA.

https://baltimore.cbslocal.com/2021/09/02/more-than-80-of-americans-have-some-immunity-to-coronavirus-blood-survey-finds/

U.S. lawmakers question FTC's efforts to stop Illumina's deal for Grail

 

Two Republican lawmakers on Thursday questioned the Federal Trade Commission's efforts to unwind life science company Illumina Inc's $7.1 billion acquisition of Grail Inc, alleging the regulator was not following a normal path in its work.

Members of Congress Jim Jordan and Darrell Issa wrote in a letter to FTC Chair Lina Khan that agency actions related to the deal require congressional oversight, demanding documents related to the FTC's work.

"The FTC's approach to the Illumina-GRAIL merger departs from its typical enforcement process and raises questions about the Commission's interference in the case," the Sept. 2 letter said.

The FTC confirmed it received the letter but declined further comment.

Among their complaints, the members of Congress alleged that the FTC filed for an injunction in federal court to give it time to litigate the case before the FTC's own internal administrative court "to avoid speedily resolving novel legal issues under U.S. law in a forum - federal district court - where the FTC was more likely to lose."

The FTC has argued that cancer test detection company Grail and its competitors rely on San Diego, California-based Illumina's DNA sequencing technology. They alleged that Illumina's purchase of Grail would give the company the "incentive and ability to foreclose downstream rivals."

https://www.marketscreener.com/quote/stock/ILLUMINA-INC-9659/news/Illumina-U-S-lawmakers-question-FTC-s-efforts-to-stop-Illumina-s-deal-for-Grail-36314564/

What to expect at the FDA's two-day meeting on gene therapy safety

 Over the past several years, drugmakers have inundated the Food and Drug Administration with scores of applications to begin clinical trials of experimental gene therapies for a wide array of inherited diseases. 

The wave of submissions reflects a research boom that's brought two gene therapies to market in the U.S. and numerous others into later stages of testing. Awash in funding, new gene therapy biotechs have proliferated and, with them, a pipeline that by one count now exceeds 300 would-be treatments.

Yet, while gene therapy has made huge strides since its emergence in the late 1980s, many scientific questions remain, particularly now that more and more patients are being treated in clinical trials. 

To help answer some of those questions, the FDA has asked a panel of gene therapy experts to evaluate an array of safety risks to the complex and cutting-edge treatments. 

The meeting, which will be held virtually Thursday and Friday, could help the agency set new guardrails for running gene therapy trials and for monitoring participants afterwards. And for a field that's advancing quickly, the discussion could serve as a reminder of the risks of treatments often characterized by their potential for dramatic benefit.

Here's what to expect: 

What will the committee be discussing? 

The FDA is focusing the discussion on the safety risks presented by one of the more commonly studied types of gene therapy, namely treatments delivered by a harmless virus called adeno-associated virus, or AAV. 

AAVs are a popular tool for shuttling functional copies of genes into the cells that need them. Luxturna, a blindness treatment developed by Spark Therapeutics that became the first gene therapy approved in the U.S., uses AAV, as does Zolgensma, a therapy for spinal muscular atrophy sold by Novartis. Many other gene therapies that are still in testing do as well. 

Over the course of the two days, the panel will discuss the cancer risk posed by AAV gene therapy, as well as toxicity to the liver and brain that's been observed in animal testing and in humans.

FDA officials and researchers from top academic centers will present on each safety concern, after which the panel will debate how best to assess that risk and whether it can be prevented or mitigated by better treatment or study design. 

Who's speaking? 

The roster of speakers is headlined by Jim Wilson, a star gene therapy researcher with the University of Pennsylvania. Wilson led the gene therapy trial that resulted in the 1999 death of study volunteer Jesse Gelsinger. Since that tragedy, however, he's become a pioneer in the development of AAV vectors, forming multiple biotechs like RegenxBio and Passage Bio in the process. 

But as use of AAV vectors has become more widespread and developers test higher and higher doses, Wilson has also been a voice of caution. A paper his group at UPenn published three years ago described liver and nerve damage in animal experiments, a finding his team used to call for researchers to do more monitoring. Wilson will deliver two separate presentations at the meeting, respectively focused on liver or neurological side effects in preclinical studies. 

The meeting will feature talks from other gene therapy researchers and investigators as well. Ronald Crystal, the chair of genetic medicine at Weill Cornell who has worked on gene therapy since 1987, will discuss the use of AAV vectors in the brain. Lindsey George, a Children's Hospital of Philadelphia investigator involved in multiple hemophilia gene therapy trials, will talk about liver toxicity observed in human studies.  

Only one industry representative, from Novartis, will present to the panel. That talk will center around three cases of a rare clotting syndrome that were observed in post-marketing surveillance of Zolgensma last year. A warning alerting doctors of the potentially serious side effect, known as thrombotic microangiopathy, is now in Zolgensma's prescribing information. 

Why is this meeting being held? 

Safety concerns have dogged gene therapy ever since a series of setbacks two decades ago temporarily halted research and chilled further investment. Improved delivery tools, such as AAV, have helped address some of those concerns, and AAVs are now used in dozens of clinical trials.

But as the use of AAVs widened, more serious side effects have been reported, reviving safety questions and grabbing the attention of regulators.

The FDA cited recent research, for instance, that found roughly a third of AAV gene therapy trials had a "treatment-emergent serious adverse event." 

Some of those have led to tragic results, or to significant patient concerns. In a clinical trial of an Audentes Therapeutics gene therapy for a rare neuromuscular disease, liver-related side effects lead to the death of three patients. Immune-related side effects have occurred in testing of Duchenne muscular dystrophy gene therapies from Solid Biosciences and Pfizer as well as of a vision loss treatment from Adverum Biotechnologies.

A participant in a study of a UniQure gene therapy for hemophilia, meanwhile, was diagnosed with liver cancer, though the biotech later concluded its gene therapy was "highly unlikely" to be the cause. 

Worrisome findings have been found in animal tests with AAV vectors as well, which, taken together, has led to "questions about causality and risk mitigation," the FDA said.

What could come of the meeting?

Advisory committee meetings are just that. The FDA uses them as a sounding board for issues it's wrestling with, but it's not required to follow the advice given by the assembled experts. 

In gene therapy, though, the FDA and drugmakers are both learning as they go. The agency has firmed up its thinking on a number of topics, finalizing a slate of six guidance documents early last year, but it's still developing the rules of the road. 

The questions the FDA posed to its advisers cover a lot of ground and many are open-ended. But they give clues to the direction the agency is thinking. 

Several of the questions ask the experts whether the FDA should set an upper limit on the size of gene therapy doses due to the risk of serious brain and liver toxicity, both of which have been associated with higher doses in several instances. 

With liver toxicity, the FDA wants to know if there are patient factors other than weight that should be considered when determining a dose, a line of inquiry that could impact how clinical trials are run.

Other questions suggest the FDA is particularly interested in whether animal studies could be better designed to assess the risk of cancer or liver damage before testing in humans starts. 

https://www.biopharmadive.com/news/fda-gene-therapy-advisory-meeting-safety-preview/605922/

FDA panel to discuss boosters as Moderna seeks OK for additional shot

 

• Moderna on Wednesday said it had started an application to the Food and Drug Administration for clearance of a booster dose for its coronavirus vaccine; the same day the FDA announced it will convene an advisory committee in two weeks to discuss Pfizer’s submission for the same authorization.
• That meeting, which will take place on Sept. 17, comes just three days before the Biden administration said the general public can expect to start receiving booster doses. While health officials initially indicated the extra dose should be given eight months after a person’s initial inoculation, Biden recently suggested a timeline of as soon as five months.
• Earlier this week, the advisory panel for the Centers for Disease Control and Prevention briefly discussed boosters — or third doses, as the committee suggested they be called — in a daylong meeting, but they have yet to officially vote on their stance. The committee emphasized that, while boosters could be important, the U.S.’s “top priority should be continued vaccination of unvaccinated individuals.”

Moderna’s submission is a significant step toward a broader authorization for booster shots; one that Pfizer took on Aug. 25. As the delta variant spreads across the country, accounting for over 90% of new coronavirus infections, public health officials have pitched boosters as a way to maintain high protection against COVID-19. For some experts, however, the case isn’t as clear-cut when it comes to healthy adults.

The FDA expanded its authorization for the Pfizer and Moderna vaccines in August to allow some immunocompromised people to receive a third dose. The CDC’s director endorsed the expanded authorization, and the extra shot became available that same weekend. 

As of Aug. 30, nearly one million Americans had received a booster dose, according to CDC data. It’s not clear, however, who exactly is part of that group and if they were authorized to receive the additional dose.

Moderna’s booster would be a 50 microgram dose, rather than the 100 microgram dose used for the two doses currently authorized. The company suggested the third shot should be given six months after the first two doses, pointing to clinical data from 344 volunteers who received an additional shot. The third dose increased antibody levels to a higher point than after only two doses, “notably in older adults,” Moderna said.

Moderna will submit an application to the European Medicines Agency in the coming days, although the agency has said they want to see additional data before making any decisions. On Wednesday, the European Centre for Disease Prevention and Control made the same point and said there was no urgent need for booster doses yet.

https://www.biopharmadive.com/news/fda-panel-to-discuss-boosters-as-moderna-seeks-ok-for-additional-shot/606017/