Know More About mRNA Before Your COVID Jab

 Clinicians will start rolling up their sleeves in just a few weeks to get their first doses of COVID-19 vaccines, both of which use mRNA technology to induce an immune response.

For those who want more information on the history and science of mRNA vaccines and therapeutics before getting their jab, here's a primer.

How It Works

Biologically, messenger RNA is transcribed from DNA and travels into a cell's cytoplasm where it's translated by ribosomes into proteins.

For the Pfizer/BioNTech and Moderna vaccines, the synthesized mRNA is cloaked in a lipid nanoparticle in order to evade the immune system when it's injected. Once it's inside a cell, the ribosomes will get to work pumping out the spike protein of SARS-CoV-2.

The immune system then mounts a response to that protein, conferring immunity to the virus without ever having been infected by it.

Essentially, instead of pharma producing the proteins via an expensive and difficult process, mRNA enlists the body to do the work. The capability to produce mRNA so rapidly is one reason these vaccines are out front in the global race for a COVID-19 vaccine.

Never Been Done Before?

That's not completely true. While an mRNA vaccine has never been on the market anywhere in the world, mRNA vaccines have been tested in humans before, for at least four infectious diseases: rabies, influenza, cytomegalovirus, and Zika.

In 2017, German biotech CureVac published results in The Lancet for a phase I trial of its mRNA rabies vaccine, and in January of this year the company issued results via press release from a phase I trial of its low-dose rabies mRNA vaccine.

Last year, Moderna and German researchers published the phase I results of two mRNA vaccines against influenza. In January, Moderna announced results of its phase I study of an mRNA vaccine against cytomegalovirus, and just this past April as the pandemic raged, the company reported interim data from its mRNA vaccine against Zika.

In a paper in Nature Reviews Drug Discovery, Drew Weissman, MD, PhD, of the University of Pennsylvania in Philadelphia and an early pioneer of mRNA technology, and colleagues wrote that early results from the rabies and flu mRNA vaccines "were somewhat modest, leading to more cautious expectations about the translation of preclinical success to the clinic."

The team noted that in both trials, immunogenicity was "more modest in humans than was expected based on animal models, a phenomenon also observed with DNA-based vaccines, and the side effects were not trivial."

Some indication of immunogenicity can also be gleaned from the COVID vaccine trials. Topline final results with the Pfizer/BioNTech showed 95% effectiveness in preventing symptomatic infection within 2 months of the second dose. Moderna's vaccine showed an efficacy rate of 94.1% in final phase III results. Both products appeared very effective in preventing severe illness as well as more moderate cases.

Durability of these effects remains an open question. However, follow-up data from a phase I study of Moderna's product, spanning 4 months after the first dose, showed a persistent neutralizing antibody response, though with modest declines over that period, particularly in older participants.

What Do We Know About Safety?

While the flu and rabies vaccines appeared to be "safe and reasonably well tolerated," Weissman and colleagues wrote, trials did show "moderate and in rare cases severe injection site or systemic reactions."

Their chief safety concerns, which they said should be closely watched in future trials, were about local and systemic inflammation, as well as keeping tabs on the "expressed immunogen" and on any auto-reactive antibodies.

"A possible concern could be that some mRNA-based vaccine platforms induce potent type I interferon responses, which have been associated not only with inflammation but also potentially with autoimmunity," they wrote. "Thus, identification of individuals at an increased risk of autoimmune reactions before mRNA vaccination may allow reasonable precautions to be taken."

The authors also noted that extracellular RNA could contribute to edema, and cited a study that showed it "promoted blood coagulation and pathological thrombus formation."

"Safety will therefore need continued evaluation as different mRNA modalities and delivery systems are utilized for the first time in humans and are tested in larger patient populations," they wrote in the paper, which was published in 2018.

Systemic effects have definitely been seen with the two mRNA COVID vaccines, with news reports quoting participants as complaining of symptoms like "bad flu." While Pfizer/BioNTech reported no serious safety concerns with their COVID-19 vaccine, patients did experience grade 3 fatigue and headache at rates of 3.8% and 2%, respectively.

Moderna did not release figures for adverse events in announcing final topline results, but said there were "no new serious safety concerns." Interim data from the company's phase III trial, analyzed when 95 infections had been recorded, did include adverse event rates: fatigue (9.7%), myalgia (8.9%), arthralgia (5.2%), headache (4.5%), pain (4.1%), and erythema/redness at the injection site (2.0%).

Why Did Earlier Vaccines Stall?

"A major factor is that there's not a sense of urgency," Dennis Burton, PhD, of Scripps Translational Research Clinic in La Jolla, California, told MedPage Today.

Zika has been relatively contained; rabies vaccines are already sufficiently effective; and influenza remains a difficult target, Burton said.

While tolerability may have been an issue, safety wasn't, he said. "There's no risk of incorporation into host chromosomes, and levels of mRNA and protein will decline and clear."

"We know broadly that the overall approach is pretty safe," Burton said, but noted that it was important that adverse events are monitored and followed up.

He cautioned that just based on the sheer number of people who will be vaccinated for COVID-19, events will occur, and most will likely be unrelated to the vaccine. If people feel that concerns about those events are adequately addressed, they should be less likely to harbor reservations about taking the vaccine, and more inclined to help achieve the levels of herd immunity needed to end the pandemic.

"One of the things we're most concerned about is that people won't get vaccinated," he said. "But the risks of this disease are going to be way higher than the risks associated with vaccination."

What Else Do I Need to Know?

Introducing synthetic mRNA into cells also holds promise as a type of replacement therapy for diseases in which production of vital proteins is inadequate or defective. It could thus hold advantages over gene therapies and protein replacement: less risky than the former, less frequent dosing than the latter, and cheaper than either.

Preclinical work on therapeutic mRNA goes back at least to 1990, with successful protein production seen in mice. Two years later, a study showed that mRNA injected into the hypothalamus of rats with a genetic mutation enabled production of vasopressin and reversed their diabetes.

But those early results didn't garner substantial interest in mRNA therapeutics due to concerns about mRNA instability, high innate immunogenicity, and inefficient delivery, Weissman and colleagues wrote. "Instead, the field pursued DNA-based and protein-based therapeutic approaches."

Finally, in 2005, Weissman and Katalin Kariko, who is now a senior vice president at BioNTech, modified the mRNA so that it could evade immune detection and boost protein production, according to an article in STAT. This is considered one of the groundbreaking moments in mRNA therapeutics, experts told STAT.

Since then, the technology has been used not just in vaccines for infectious diseases, but also as a means to rev up the immune system to battle cancer. mRNA can target tumor-associated antigens expressed mainly by cancerous cells, like certain growth factors. These therapeutic -- rather than prophylactic -- vaccines have been tested in a range of cancers, including acute myeloid leukemia, multiple myeloma, glioblastoma, melanoma, prostate cancer, and others.

There are fewer trials of regular therapeutics, but one that has garnered some attention is an mRNA heart failure therapy being developed by Moderna and AstraZeneca that encodes for vascular endothelial growth factor A. Preclinical studies showed new blood vessel creation and improved cardiac function, and a phase I study in diabetic patients published in Nature Communications in 2019 showed enhanced blood flow, which could indicate "therapeutic potential for regenerative angiogenesis."

Whether the apparent success of Pfizer and Moderna's vaccines will spark a wave of mRNA therapeutic development remains to be seen, but Burton cautioned that the coronavirus spike protein "does seem to be a particularly easy target."

"Will RNA work for all vaccines? I don't think we can say that yet," Burton said. "It's a huge leap forward. It's very quick to make and has a lot of advantages. But I think SARS-CoV-2 is an easy test relative to some of the other viruses we have to deal with."

https://www.medpagetoday.com/infectiousdisease/covid19/89998

UK recruits first global patient to antibody treatment study to protect against COVID

 The world’s first participant in a new antibody treatment study to protect against COVID-19 has been recruited at the University College London Hospitals (UCLH) NHS Foundation Trust.

The trial is for people thought to have come into contact with a confirmed COVID-19 case. The AstraZeneca study called STORM CHASER, began recruiting participants at UCLH’s new Vaccine Research Centre, and is being delivered by the NIHR.

Through the use of a monoclonal antibody, the study hopes to offer immediate protection to people who have recently been exposed to the virus and prevent them developing infection.

Antibodies are protein molecules that the body produces to help fight infections. Monoclonal antibodies are artificially produced in a laboratory and designed as possible medical treatments. Monoclonal antibodies are designed to be injected directly into the body, unlike vaccines which encourage the immune system itself to produce antibodies.

The study is one of two national priority trials focused on the treatment of two investigational antibodies, known as AZD7442. The PROVENT trial, another AstraZeneca study, is looking at the use of the long-acting antibody combination in people who may not respond to vaccination, for example someone who has a compromised immune system or are at increased risk of COVID-19 infection.

The antibodies have been engineered with AstraZeneca’s proprietary half-life extension technology to increase the durability of the therapy for six to 12 months following a single administration. The combination of two antibodies is also designed to reduce the risk of resistance developed by the SARS-CoV-2 virus.

In both studies, researchers are assessing whether the treatment reduces the risk of developing COVID-19 and/or reduces the severity of infection compared to placebo.

Key participant groups in the STORM CHASER study include healthcare workers, students living in group accommodation, and patients exposed to anyone with the SARS-CoV-2 virus which causes COVID-19, as well as residents of long-term care facilities and industrial/military settings.

Both trials are taking place at UCLH’s Vaccine Research Centre, which opened in December 2020, under the patronage of the NIHR UCLH Biomedical Research Centre, to help accelerate the development of new vaccines and treatments during the COVID-19 pandemic. The centre represents an extension of the existing NIHR UCLH Clinical Research Facility (CRF).

Prof Andrew Ustianowski, Joint National Specialty Lead for Infection, National Institute of Health Research (NIHR), and Chief Investigator of the study said:

"We have had very encouraging data on COVID-19 vaccines and these are imminently being rolled-out to our populations. We have some significant improvement in our management of those with COVID-19. What we don't yet have, but need, are interventions in the post-exposure setting. STORM CHASER is exploring the use of a combination of monoclonal antibodies given intramuscularly in those who have been exposed to SARS-CoV2 - a setting where vaccination would not have time to work and we have no other proven therapies to date. Therefore this is an important study that may have a large impact on our ability to control this infection.

"Today's announcement shows once again the UK's ability to set up world-leading research into COVID-19. It is a credit not only to the research team involved, but the thousands of people at the NIHR and the NHS who have delivered COVID-19 vaccine research in ground-breaking time."

Mene Pangalos, AstraZeneca Executive Vice President, BioPharmaceuticals Research & Development, said:

“AZD7442 has the potential to be an important preventative and therapeutic medicine against Covid-19, focusing on the most vulnerable patients. This work complements our vaccine development programme.

“The STORM CHASER trial in particular is a unique approach, with enrolment initiated on site following the identification of a confirmed case to halt the spread of Covid-19 in the facility or community. We offer our appreciation and gratitude to everyone involved in these trials, from the scientists, researchers and clinicians, to the trial participants and study sites, as we all work together to help end this pandemic.”

https://www.nihr.ac.uk/news/uk-recruits-first-global-patient-to-antibody-treatment-study-to-protect-against-covid-19/26458

Brooklyn clinics face criminal probe over unauthorized COVID-19 vaccine

 A health-care network with clinics in Boro Park, Bensonhurst and Williamsburg is under a criminal investigation for giving unauthorized COVID-19 vaccines, officials said Saturday.

ParCare Community Health Network  “may have fraudulently obtained COVID-19 vaccine, transferred it to facilities in other parts of the state in violation of state guidelines and diverted it to members of the public,” state Health Commissioner Howard Zucker said in a news release.

The statement came hours after The Post questioned a state health department spokesman about ParCare giving the coveted inoculations.

The network’s actions appear to violate the state’s plan to administer the limited supply of vaccines first to frontline healthcare workers, along with nursing home residents and staffers, the statement said.

Currently, there isn’t enough vaccine for the groups that are supposed to get it first.

“The supply of COVID-19 vaccine remains limited and has not yet met demand among the groups prioritized for initial vaccination,” Dr. Jane Zucker, the city Health Department’s assistant commissioner for immunizations said Thursday.

The news site BoroPark24 reported Dec. 21 that ParCare claimed it had received 3,500 doses of the Moderna vaccine.

ParCare shared this poster on social media announcing their authorization to administer COVID-19 vaccines.

“Hundreds of patients were already vaccinated today, and people are still coming in,” Gary Schlesinger, the CEO and president of ParCare, told the news site.

Schlesinger also said he expected to have vaccinated 500 people in Boro Park that same day.

ParCare set up a website, parcarevaccine.com, where residents could register for the vaccine.

“You have to be on that list,” Schlesinger told BoroPark24, adding he expected to get more vaccines every day. “Once you are on the list, we have to vet to make sure that you are either a healthcare worker, are over 60, or have underlying conditions. We will not give the vaccine to people who are not eligible for this first batch of the shots.”

ParCare accepts Medicare, Medicaid, and most other insurance plans, the company said.

ParCare brazenly tweeted photos Monday showing boxes of the Moderna vaccine wrapped with ice packs and then in a refrigerator.

“ONE SMALL INJECTION CAN MAKE A DIFFERENCE FOR THE ENTIRE COMMUNITY!” it tweeted.

Schlesinger is politically well-connected in the Orthodox Jewish community. He has cultivated ties to Mayor de Blasio, Attorney General Letitia James, Brooklyn District Attorney Eric Gonzalez, and Brooklyn borough president and mayoral candidate Eric Adams, sources said. 

A ParCare ad claimed  “the FDA authorized” the network to receive “a minimal number of COVID-19 vaccines.”

“The vaccines will be made available on a first-come, first-serve (sic) basis,” the ad says.

It adds the vaccines will be given “Only for people in the following categories,” and lists: “Elderly, high risk, underlying conditions.”

One community member told The Post his father, in his 60s, received the vaccine at ParCare’s Williamsburg clinic.

“It’s known in the community you can get a vaccine if you want,” the resident said, adding “it’s a mystery”  how the clinic obtained the supply.

“We take this very seriously and DOH will be assisting State Police in a criminal investigation into this matter. Anyone found to have knowingly participated in this scheme will be held accountable to the fullest extent of the law,” the state health commissioner said.

Schlesinger could not immediately be reached for comment.

https://nypost.com/2020/12/26/brooklyn-clinics-face-criminal-probe-over-covid-19-vaccines/

BionTech CEO says will work with others to boost vaccine capacity

 

BioNTech Chief Executive Ugur Sahin said his company would be open to cooperating with others as it looks to increase production capacity for its COVID-19 vaccine developed with Pfizer and was considering opening an office in Turkey.

Sahin repeated BioNTech aimed to distribute 1.3 billion doses of its vaccine by the end of 2021 and that 70% of the world needed to be vaccinated by next winter to go back to "normal life", according to an interview with Turkey's state-run Anadolu news agency.

"We want to produce more than 1 billion doses with Pfizer next year. We need to distribute them to over 80 countries," he was cited as saying. "This is not easy. Vaccines are made in a complex manner. We will start cooperating with other companies again," he added.

"If we can carry out our plans on how to increase capacity, we can disclose it in January or February. I believe we can increase it. We don't have a guaranteed plan yet."

Ankara has agreed to buy 4.5 million doses of the BioNTech and Pfizer vaccine, with an option to procure 30 million more doses later.

Sahin, the son of a Turkish immigrant to Germany, told Anadolu BioNTech was in talks with Turkey's state scientific agency Tubitak, and would aim to deliver the 30 million doses to the country by the end of 2021.

"It is a great joy to be able to help people in Turkey," Sahin was quoted as saying by Anadolu.

"We also want to carry out research in Turkey. We have talks with Tubitak, we have started working with some professors at universities. We want to open a branch of the BioNTech company in Turkey," he said, adding he hoped to start clinical work on cancer research in the country in the summer of 2021.

Turkey has also agreed to buy 50 million doses of China's Sinovac vaccine, CoronaVac, and a first shipment of 3 million doses of CoronaVac arrives on Monday.

https://www.marketscreener.com/quote/stock/SINOPHARM-GROUP-CO-LTD-5774274/news/BionTech-CEO-says-will-work-with-others-to-boost-vaccine-capacity-Anadolu-32088249/

U.S. bracing for post-Christmas COVID-19 surge

 

• Despite warnings from health officials to limit travel amid rising COVID-19 cases in the U.S., more than 6.7M people have passed through TSA checkpoints in the seven days heading into Christmas, 
• That is over a 3% increase for the same period through Thanksgiving Day last month. In two weeks, the post-Thanksgiving COVID-19 surge led to a 20% rise in new COVID-19 cases, with a 21% rise in hospitalizations and a 39% jump in fatalities.
• "We had Thanksgiving, we had Labor Day, we had Halloween, and each one of these events brought lots of people together and just gave the virus more fuel to move through the population," CNN quoted a health expert as saying. 
• The fresh concerns over another spike in case numbers emerge as a new COVID-19 variant detected in the U.K., which has prompted many countries to impose travel restrictions on the country. Last week, the CDC warned that the new variant could already be circulating in the U.S. without notice, given the insufficient number of COVID-19 cases that have been sequenced across the country. 
• Meanwhile, the investors appear to be bullish over the companies focused on COVID-19 testing and treatments. Despite vaccine hopes, the ETFMG Treatments, Testing, and Advancements ETF (NYSEARCA:GERM) has returned +25.1% over the past six months, outperforming the +12.6% rise in the iShares Nasdaq Biotechnology ETF (NASDAQ:IBB).
• Last week the analysts at JPMorgan Chase upgraded their price targets for Quest Diagnostics (NYSE:DGX) and Laboratory Corporation of America (NYSE:LH), anticipating ‘better than expected COVID-19 molecular testing volumes’, to offset the ‘weaker than expected organic testing volume.’
• https://seekingalpha.com/news/3647428-u-s-is-bracing-for-post-christmas-covidminus-19-surge

COVID-19 Antibody Test For Blood, Platelet and Plasma Donations

 COVID-19 is caused by a coronavirus called SARS-CoV-2, but most people use coronavirus and COVID-19 interchangeably. Since the beginning of the coronavirus pandemic, the American Red Cross has been a nationwide leader in supporting the lifesaving efforts those battling the virus. In early spring, the Red Cross began implementing additional safety measures including taking the temperature of all potential donors and requiring that masks be worn at all donation sites by both donors and staff. In March of this year, the Red Cross also started collecting convalescent plasma from donors who had already recovered from SARS-CoV-2 infection to support hospitals evaluating its use as possible treatment for critically ill coronavirus patients. At this time, the Red Cross was only testing convalescent plasma for COVID-19 antibodies. In June 2020, the Red Cross began testing tingblood, platelet and plasma donations for COVID-19 antibodies as an additional health service to our donors.

What Is Antibody Testing?

When a person is sick, their immune system develops antibodies to the virus or pathogen causing the illness. COVID-19 antibody tests detect the presence of antibodies that may fight off SARS-CoV-2 infection. A positive antibody test result indicates that an individual may have had previous exposure to the virus that causes COVID-19 and their body has developed specific antibodies to the virus. The test does not diagnose or confirm an infection with coronavirus. Tests to diagnose coronavirus infection look for the presence of viral nucleic acids and are performed by one’s health care provider. It is currently unknown whether the presence of COVID-19 antibodies provides immunity to future infection, although it has been shown to be the case with related viruses for a period of time.

The Red Cross hopes that the temporary addition of COVID-19 antibody testing will give our donors helpful information that may indicate if their immune system has produced antibodies to the coronavirus, regardless of whether they developed symptoms.

What You Should Know About Red Cross Antibody Testing

When potential donors present to Red Cross donation sites, the health and safety of the donors, volunteers, employees, and patients is our highest priority. Each collected blood donation is tested for many different infectious diseases before it can be transfused to a patient. Some of these tests are antibody tests. The COVID-19 antibody test has been added as one of these tests. Testing has become widely available and provides valuable insight into the prevalence and spread of the disease in our population. As of June 15, 2020, for a limited all blood product donations will undergo COVID-19 antibody testing for a limited time.

Results will be available seven to 10 days after the donation is completed. Donors will be able to view the results of their COVID-19 antibody test, as well as other vital signs obtained during their pre-donation screening, in both the Blood Donor App and on RedCrossBlood.org. The results of the antibody test will read either positive (COVID-19 antibodies were presumptively detected), negative (COVID-10 antibodies were presumptively not detected), or not available. Results may not be available if the sample could not be tested.

Individuals who have a positive antibody test result may be eligible to participate in the convalescent plasma donation program, though additional donor pre-qualification via the convalescent plasma donor eligibility form is needed. More information about the program and the donor eligibility form can be found here.

https://www.redcrossblood.org/local-homepage/news/article/covid-19-antibody-test-for-blood--platelet-and-plasma-donations.html

LA County taps labs to probe for variant coronavirus strain

 As demand for precious hospital space continued to rise on Friday, Dec. 25, Los Angeles county public health officials were asking testing labs to look for a variant of COVID-19  —  reported in the United Kingdom — that appears to be more transmissible than other strains.

In a memo issued Thursday, public health officials asked that laboratories help with “surveillance to detect the variant strain and to report any occurrence” of it to them.

This strain is believed to be potentially more transmissible than others that have been circulating, but there is no evidence that it results in more severe illness or greater risk of death, according to the Centers for Disease Control and Prevention.

The county memo, issued to healthcare providers, came as Los Angeles county experiences a record-breaking surge that on Thursday resulted in a report that 148 people who tested positive for COVID-19 died in a single day.

While holidays such as Thanksgiving — during which families and friends typically gather — may be contributing to the high numbers, public health officials in Los Angeles county have also been perplexed by the intensity of the latest surge in cases.

The surge appears to be continuing into the Christmas holiday, during which large numbers of people have flocked to outdoor malls to shop. Some also turned out to attend indoor religious services, but in much smaller numbers than in previous years.

Meanwhile, public officials have been trying to learn more about the variant strain found in the United Kingdom that has been especially prevalent in London and in the southeast.

The Centers for Disease Control and Prevention recently issued an advisory saying that this  “variant strain has been predicted to potentially be more rapidly transmissible than other circulating strains of SARS-CoV-2,” although there is no evidence this strain will cause more severe illness or greater risk of death.

Public health officials also say there is no evidence at this time that the Pfizer and Moderna vaccines now being administered against the virus would be less effective against this variant.

Due to a Spectrum communications service outage, county public health officials said Friday that they were unable to report the daily numbers for COVID-19 cases and deaths. Instead, that information will be included in Saturday’s daily report.

Although there were no numbers reported by the county, state data on hospitalizations again showed and increase. The state reported that 6,770 people are hospitalized, with 1,335 of them in the Intensive Care Unit. That is up by 62 from the previous numbers of 6,708 people in hospitals, with 1,329 of them in the ICU.

In total, by Christmas Eve, Public Health officials had identified 677,299 positive cases of COVID-19 across all of L.A. County, with a total of 9,299 deaths.

With the rising hospitalization numbers, public officials have also warned of the crisis reaching a more dire stage, in which overwhelmed hospitals that are already often a capacity may no longer be able to provide full care to all of their patients.

Planning for rationing care, which involves deciding which patients to provide care to over others, is already underway, public officials have said.

Los Angeles Mayor Eric Garcetti also warned of this possibility that care will need to be rationed, in his briefing on Wednesday, ahead of the Christmas holiday.

“If we continue to spread this virus, if we see a linear growth of this for the next two weeks, we will not have enough medical staff to treat everyone at hospitals may soon be in the position of having to ration care,” he said. “That means the doctors will be forced to determine who lives and who dies, and more Angelenos will lose their lives, not just the COVID-19, but to call emergencies.”

https://www.eastbaytimes.com/2020/12/26/la-county-taps-labs-to-probe-for-variant-coronavirus-strain/