 Your new post is loading...
|
Scooped by
Juan Lama
|
The goal of any vaccine is to induce long-lived plasma cells (LLPC) to provide life-long protection. Natural infection by influenza, measles, or mumps viruses generates bone marrow (BM) LLPC similar to tetanus vaccination which affords safeguards for decades. Although the SARS-CoV-2 mRNA vaccines protect from severe disease, the serologic half-life is short-lived even though SARS-CoV-2-specific plasma cells can be found in the BM. To better understand this paradox, we enrolled 19 healthy adults at 1.5-33 months after SARS-CoV-2 mRNA vaccine and measured influenza-, tetanus-, or SARS-CoV-2-specific antibody secreting cells (ASC) in LLPC (CD19−) and non-LLPC (CD19+) subsets within the BM. All individuals had IgG ASC specific for influenza, tetanus, and SARS-CoV-2 in at least one BM ASC compartment. However, only influenza- and tetanus-specific ASC were readily detected in the LLPC whereas SARS-CoV-2 specificities were mostly excluded. The ratios of non-LLPC:LLPC for influenza, tetanus, and SARS-CoV-2 were 0.61, 0.44, and 29.07, respectively. Even in five patients with known PCR-proven history of infection and vaccination, SARS-CoV-2-specific ASC were mostly excluded from the LLPC. These specificities were further validated by using multiplex bead binding assays of secreted antibodies in the supernatants of cultured ASC. Similarly, the IgG ratios of non-LLPC:LLPC for influenza, tetanus, and SARS-CoV-2 were 0.66, 0.44, and 23.26, respectively. In all, our studies demonstrate that rapid waning of serum antibodies is accounted for by the inability of mRNA vaccines to induce BM LLPC. Preprint available in medRxiv (March 5, 2024): https://doi.org/10.1101/2024.03.02.24303242
|
|
Scooped by
Juan Lama
|
In vitro-transcribed (IVT) mRNAs are modalities that can combat human disease, exemplified by their use as vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). IVT mRNAs are transfected into target cells, where they are translated into recombinant protein, and the biological activity or immunogenicity of the encoded protein exerts an intended therapeutic effect1,2. Modified ribonucleotides are commonly incorporated into therapeutic IVT mRNAs to decrease their innate immunogenicity3–5, but their effects on mRNA translation fidelity have not been fully explored. Here we demonstrate that incorporation of N1-methylpseudouridine into mRNA results in +1 ribosomal frameshifting in vitro and that cellular immunity in mice and humans to +1 frameshifted products from BNT162b2 vaccine mRNA translation occurs after vaccination. The +1 ribosome frameshifting observed is probably a consequence of N1-methylpseudouridine-induced ribosome stalling during IVT mRNA translation, with frameshifting occurring at ribosome slippery sequences. However, we demonstrate that synonymous targeting of such slippery sequences provides an effective strategy to reduce the production of frameshifted products. Overall, these data increase our understanding of how modified ribonucleotides affect the fidelity of mRNA translation, and although there are no adverse outcomes reported from mistranslation of mRNA-based SARS-CoV-2 vaccines in humans, these data highlight potential off-target effects for future mRNA-based therapeutics and demonstrate the requirement for sequence optimization. A study demonstrates that nucleotide modifications in mRNA-based therapeutics can lead to +1 ribosomal frameshifting during translation, yielding products that can trigger immune responses. Published in Nature (Dec. 6, 2023): https://doi.org/10.1038/s41586-023-06800-3
|
|
Scooped by
Juan Lama
|
Background: Subvariants of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) omicron XBB-lineage have the potential to escape immunity provided by prior infection or vaccination. For Covid-19 immunizations beginning in the Fall 2023, the U.S. FDA has recommended updating to a monovalent omicron XBB.1.5-containing vaccine. Methods: In this ongoing, phase 2/3 study participants were randomized 1:1 to receive 50-µg doses of mRNA-1273.815 monovalent (50-µg omicron XBB.1.5 spike mRNA) or mRNA-1273.231 bivalent (25-µg omicron XBB.1.5 and 25-µg omicron BA.4/BA.5 spike mRNAs) vaccines, administered as 5th doses, to adults who previously received a primary series and 3rd dose of an original mRNA coronavirus disease 2019 (Covid-19) vaccine, and a 4th dose of a bivalent (omicron BA.4/BA.5 and original SARS-CoV-2) vaccine. Interim safety and immunogenicity data 15 days post-vaccination are presented. Results: In April 2023, participants received mRNA-1273.815 (n=50) and mRNA-1273.231 (n=51). The median intervals from the prior dose of BA.4/BA.5-containing bivalent vaccine were 8.2 and 8.3 months for the mRNA-1273.815 and mRNA-1273.231 groups, respectively. Both vaccines increased neutralizing antibody (nAb) geometric mean titers against all variants tested at day 15 post-booster nAb compared to pre-booster levels. Geometric mean fold-rises from pre-booster titers after the monovalent booster were numerically higher against XBB.1.5, XBB.1.16 and SARS-CoV-2 (D614G) than those of the bivalent booster and were comparable against BA.4/BA.5 and BQ1.1 variants for both vaccines. The monovalent vaccine also elicited nAb responses against omicron XBB.2.3.2, EG.5.1, FL.1.5.1 and BA.2.86 that were similar to those against XBB.1.5 in a subset (n=20) of participants. The occurrence of solicited adverse reactions and unsolicited adverse events were overall similar to those previously reported for the original mRNA-1273 50-µg and omicron BA.4/BA.5-containing bivalent mRNA-1273 vaccines. Conclusion: In this interim analysis, XBB.1.5-containing monovalent and bivalent vaccines elicited potent neutralizing responses against variants of the omicron XBB-lineage (XBB.1.5, XBB.1.6, XBB.2.3.2, EG.5.1, and FL.1.5.1) as well as the recently emerged BA.2.86 variant. The safety profile of the XBB.1.5-containing vaccine was consistent with those of prior vaccines. These results overall indicate that the XBB.1.5-containing mRNA-1273.815 vaccine has the potential to provide protection against these emerging variants and support the Covid-19 vaccine update in 2023-2024 to a monovalent XBB.1.5-containing vaccine. Preprint avilable in medRxiv (Sept. 7, 2023): https://doi.org/10.1101/2023.08.22.23293434
|
|
Scooped by
Juan Lama
|
Using mRNA tailored to each patient’s tumor, the vaccine may have staved off the return of one of the deadliest forms of cancer in half of those who received it. Five years ago, a small group of cancer scientists meeting at a restaurant in a deconsecrated church hospital in Mainz, Germany, drew up an audacious plan: They would test their novel cancer vaccine against one of the most virulent forms of the disease, a cancer notorious for roaring back even in patients whose tumors had been removed. The vaccine might not stop those relapses, some of the scientists figured. But patients were desperate. And the speed with which the disease, pancreatic cancer, often recurred could work to the scientists’ advantage: For better or worse, they would find out soon whether the vaccine helped. On Wednesday, the scientists reported results that defied the long odds. The vaccine provoked an immune response in half of the patients treated, and those people showed no relapse of their cancer during the course of the study, a finding that outside experts described as extremely promising. The study, published in Nature, was a landmark in the yearslong movement to make cancer vaccines tailored to the tumors of individual patients. Researchers at Memorial Sloan Kettering Cancer Center in New York, led by Dr. Vinod Balachandran, extracted patients’ tumors and shipped samples of them to Germany. There, scientists at BioNTech, the company that made a highly successful Covid vaccine with Pfizer, analyzed the genetic makeup of certain proteins on the surface of the cancer cells. New Developments in Cancer Research Progress in the field. In recent years, advancements in research have changed the way cancer is treated. Here are some recent updates: Cancer vaccines. A pancreatic cancer vaccine provoked an immune response in half of the patients treated in a small trial, a finding that experts described as very promising. The study was a landmark in the movement to make cancer vaccines tailored to the tumors of individual patients. Ovarian cancer. Building on evidence that ovarian cancer most often originates in the fallopian tubes, not the ovaries, the Ovarian Cancer Research Alliance is urging even women who do not have a genetically-high risk for ovarian cancer — that is, most women — to have their fallopian tubes surgically removed if they are finished having children and are planning a gynecologic operation anyway. Rectal cancer. A small trial that saw 18 rectal cancer patients taking the same drug, dostarlimab, appears to have produced an astonishing result: The cancer vanished in every single participant. Experts believe that this study is the first in history to have achieved such results. Using that genetic data, BioNTech scientists then produced personalized vaccines designed to teach each patient’s immune system to attack the tumors. Like BioNTech’s Covid shots, the cancer vaccines relied on messenger RNA. In this case, the vaccines instructed patients’ cells to make some of the same proteins found on their excised tumors, potentially provoking an immune response that would come in handy against actual cancer cells. “This is the first demonstrable success — and I will call it a success, despite the preliminary nature of the study — of an mRNA vaccine in pancreatic cancer,” said Dr. Anirban Maitra, a specialist in the disease at the University of Texas MD Anderson Cancer Center, who was not involved in the study. “By that standard, it’s a milestone.” The study was small: Only 16 patients, all of them white, were given the vaccine, part of a treatment regimen that also included chemotherapy and a drug intended to keep tumors from evading people’s immune responses. And the study could not entirely rule out factors other than the vaccine having contributed to better outcomes in some patients. “It’s relatively early days,” said Dr. Patrick Ott of the Dana-Farber Cancer Institute. Beyond that, “cost is a major barrier for these types of vaccines to be more broadly utilized,” said Dr. Neeha Zaidi, a pancreatic cancer specialist at the Johns Hopkins University School of Medicine. That could potentially create disparities in access. But the simple fact that scientists could create, quality-check and deliver personalized cancer vaccines so quickly — patients began receiving the vaccines intravenously roughly nine weeks after having their tumors removed — was a promising sign, experts said. Since the beginning of the study, in December 2019, BioNTech has shortened the process to under six weeks, said Dr. Ugur Sahin, a co-founder of the company, who worked on the study. Eventually, the company intends to be able to make cancer vaccines in four weeks. And since it first began testing the vaccines about a decade ago, BioNTech has lowered the cost from roughly $350,000 per dose to less than $100,000 by automating parts of production, Dr. Sahin said. A personalized mRNA cancer vaccine developed by Moderna and Merck reduced the risk of relapse in patients who had surgery for melanoma, a type of skin cancer, the companies announced last month. But the latest study set the bar higher by targeting pancreatic cancer, which is thought to have fewer of the genetic changes that would make it ripe for vaccine treatments. In patients who did not appear to respond to the vaccine, the cancer tended to return around 13 months after surgery. Patients who did respond, though, showed no signs of relapse during the roughly 18 months they were tracked. Intriguingly, one patient showed evidence of a vaccine-activated immune response in the liver after an unusual growth developed there. The growth later disappeared in imaging tests. “It’s anecdotal, but it’s nice confirmatory data that the vaccine can get into these other tumor regions,” said Dr. Nina Bhardwaj, who studies cancer vaccines at the Icahn School of Medicine at Mount Sinai. Scientists have struggled for decades to create cancer vaccines, in part because they trained the immune system on proteins found on tumors and normal cells alike. Tailoring vaccines to mutated proteins found only on cancer cells, though, potentially helped provoke stronger immune responses and opened new avenues for treating any cancer patient, said Ira Mellman, vice president of cancer immunology at Genentech, which developed the pancreatic cancer vaccine with BioNTech. “Just establishing the proof of concept that vaccines in cancer can actually do something after, I don’t know, thirty years of failure is probably not a bad thing,” Dr. Mellman said. “We’ll start with that.” Study cited published in Nature (May 10, 2023): https://doi.org/10.1038/s41586-023-06063-y
|
|
Scooped by
Juan Lama
|
US biotech company Moderna on Tuesday announced positive interim trial results for its vaccine against respiratory syncytial virus (RSV) in adults over the age of 60. There are no jabs currently available for the virus, which is a top cause of lower respiratory diseases, commonly leading to bronchiolitis in children and pneumonia in the elderly. However numerous vaccines and treatments are under development, most notably by Moderna's rival COVID-19 vaccine maker Pfizer. Moderna's vaccine was found to be nearly 84 percent effective against RSV-linked diseases in Phase III trials—the final stage of human testing—the firm said in a statement. The trial of the vaccine, which uses the new mRNA technology from Moderna's COVID jab, involves some 37,000 adults over 60 in 22 countries including the United States. The company released the findings of an interim analysis, which has not been peer-reviewed. In the placebo group, there were 55 cases of RSV-linked lower respiratory tract disease with at least two symptoms, compared to nine in the group that received the vaccine, it said. The vaccine had no serious side effects, the company added. Moderna plans to apply for regulatory approval for the vaccine in the US, Europe and other regions in the coming months. This could make it available for the RSV season in the Northern Hemisphere's winter this year, Moderna's chief medical officer Paul Burton told AFP. The company is also testing the vaccine for use in children, but those trials are still at the first phase. 'Good news' In high-income countries, RSV caused 5.2 million cases of severe disease among adults over 60 in 2019, Moderna said. Up to 30,000 elderly patients die every year in G7 countries due to the virus, Burton added. He said that the number of doses required for Moderna's vaccine was yet to determined. The positive results come after Pfizer announced in December that its own RSV vaccine for over-60s was granted priority review status by the US Food and Drug Administration. The previous month, Pfizer said another of its RSV vaccines, which is given to pregnant mothers, was effective at protecting newborns. Also in November, the European Union approved a preventative treatment which works similarly to a vaccine made by AstraZeneca and Sanofi which has been shown to prevent severe illness from RSV in infants. When asked about other RSV vaccines being developed by Moderna's rivals, Burton said "it's good news". "The public has gone seven decades with nothing" to fight the virus, and soon could have multiple options, he said. Moderna is also looking at whether the RSV jab can be combined with COVID and even influenza vaccines, after soaring cases of all three in recent months was dubbed a "tripledemic". Moderna's Press Release: https://investors.modernatx.com/news/news-details/2023/Moderna-Announces-mRNA-1345-an-Investigational-Respiratory-Syncytial-Virus-RSV-Vaccine-Has-Met-Primary-Efficacy-Endpoints-in-Phase-3-Trial-in-Older-Adults/default.aspx
|
|
Scooped by
Juan Lama
|
RNA vaccines are efficient preventive measures to combat the SARS-CoV-2 pandemic. High levels of neutralizing SARS-CoV-2-antibodies are an important component of vaccine-induced immunity. Shortly after the initial two mRNA vaccine doses, the IgG response mainly consists of the pro-inflammatory subclasses IgG1 and IgG3. Here, we report that several months after the second vaccination, SARS-CoV-2-specific antibodies were increasingly composed of non-inflammatory IgG4, which were further boosted by a third mRNA vaccination and/or SARS-CoV-2 variant breakthrough infections. IgG4 antibodies among all spike-specific IgG antibodies rose on average from 0.04% shortly after the second vaccination to 19.27% late after the third vaccination. This induction of IgG4 antibodies was not observed after homologous or heterologous SARS-CoV-2 vaccination with adenoviral vectors. Single-cell sequencing and flow cytometry revealed substantial frequencies of IgG4-switched B cells within the spike-binding memory B-cell population (median 14.4%; interquartile range (IQR) 6.7–18.1%) compared to the overall memory B-cell repertoire (median 1.3%; IQR 0.9–2.2%) after three immunizations. Importantly, this class switch was associated with a reduced capacity of the spike-specific antibodies to mediate antibody-dependent cellular phagocytosis and complement deposition. Since Fc-mediated effector functions are critical for antiviral immunity, these findings may have consequences for the choice and timing of vaccination regimens using mRNA vaccines, including future booster immunizations against SARS-CoV-2. Published in Science Immunology (Dec. 22, 2022):
|
|
Scooped by
Juan Lama
|
Vaccine makers are betting that the mRNA technology powering two successful Covid vaccines will help curb the tragic global death toll from the flu. As the world grapples with Covid-19, influenza isn’t getting much attention these days. But the flu’s global impact is staggering: three million to five million cases of severe illness every year, and up to 650,000 deaths. Every few decades, a new flu strain spills over from animals and leads to a pandemic. The deadly toll of influenza is all the more striking when you consider that we have had vaccines to fight it for eight decades. But they remain mediocre. A flu shot is good for only one flu season, and its effectiveness typically reaches somewhere between 40 and 60 percent. In some years it’s as low as 10 percent. But a new generation of highly effective flu vaccines may emerge in the next few years, based on the same mRNA technology that has protected hundreds of millions of people against Covid-19. While traditional influenza vaccines are grown for months in chicken eggs, mRNA vaccines are manufactured relatively quickly from scratch. In theory, their faster production may make them better matched to each season’s flu strains. And when they’re injected into people, they may provoke a stronger immune response than traditional flu vaccines do. Two companies — Moderna, the Massachusetts biotech company that produced one of the authorized mRNA vaccines for Covid-19, and Sanofi, a French vaccine maker — began trials for mRNA flu vaccines this summer. Pfizer and BioNTech, the companies that produced the other mRNA Covid-19 vaccine, started their own flu trial last month. And Seqirus, a vaccine producer based in England, is planning to test another mRNA vaccine for the flu early next year. No one can say for sure how well any of these four seasonal flu vaccines will turn out, but many experts are optimistic. And further down the line, mRNA technology may be tailored to make vaccines that work for years against a wide range of influenza strains. “I am beyond excited for the future of flu vaccination,” said Jenna Bartley, an immunologist at the University of Connecticut. No one can say for sure how well any of these four seasonal flu vaccines will turn out, but many experts are optimistic. And further down the line, mRNA technology may be tailored to make vaccines that work for years against a wide range of influenza strains. “I am beyond excited for the future of flu vaccination,” said Jenna Bartley, an immunologist at the University of Connecticut. The 1918 influenza pandemic was the worst in modern history, killing somewhere between 50 million and 100 million people. As the death toll climbed, doctors responded by inoculating people by the thousands with an assortment of experimental vaccines. None of them worked. Scientists at the time wrongly believed that disease was caused by bacteria, not viruses. That error led them to make vaccines from the microbes they gathered in the sputum of flu patients. The vaccines were useless at mounting an immune defense against the viral disease. It was not until 1933 that British virologists isolated the influenza virus, finally making it possible to design an effective vaccine. Researchers injected influenza viruses into chicken eggs, where they multiplied. Once they had extracted and purified the new viruses, they killed them with chemicals, and injected the inactivated viruses into people. The United States licensed the first commercial influenza vaccine in 1945. The Nobel-prize-winning virologist Wendell Stanley hailed the milestone, declaring that the vaccine would prevent influenza from ever again becoming “one of the great destroyers of human life.” But the vaccine didn’t quite live up to Dr. Stanley’s hopes. Influenza outfoxed it with an awesome power to mutate. During an influenza infection, cells in our airway begin copying the virus’s genome, allowing it to proliferate. The copying process results in lots of genetic errors. Sometimes these mutations will enable the virus to escape the body’s immune response spurred by a vaccine. Flu viruses also have another route to rapid evolution. If two types of flu viruses infect the same cell, it can produce a genetic hybrid, which may evade vaccine-triggered immunity even more successfully. This extraordinary capacity for change also explains why several strains of flu may circulate in a single flu season, and new strains may rise to dominance the following year. “The flu virus, for lack of a better word, is just kind of a jerk,” Dr. Bartley said. Vaccine makers have responded by including up to four different strains in their annual formulations. But because producing vaccines in chicken eggs is such a slow process, scientists must choose which strains to include several months before a flu season, often leading to a mismatch when the shape-shifting virus actually arrives. “It’s an educated guessing game,” said Dr. Alicia Widge, an immunologist at the National Institutes of Health’s Vaccine Research Center. “We’re always catching up with the virus.” Between 2004 and 2019, the effectiveness of the flu vaccine ranged from as high as 60 percent to as low as 10 percent. Even that modest protection translates into a lot of benefit, however, because so many people get the flu every year. In addition to lowering the odds of getting infected, the vaccine also lowers the chances that people sick with the flu have to go to the hospital. In the 2018-19 flu season, the flu vaccine — with an effectiveness of just 29 percent — prevented an estimated 4.4 million illnesses in the United States alone, plus 58,000 hospitalizations and 3,500 deaths, according to one study. If scientists could make more robust flu vaccines, they could potentially save thousands of additional lives. “The bottom line is that the flu vaccines we have aren’t good enough,” said Nicholas Heaton, a virologist at Duke University School of Medicine.....
|
|
Scooped by
Juan Lama
|
Moderna receives FDA Fast Track designation for Respiratory Syncytial Virus (RSV) vaccine (mRNA-1345), its investigational single-dose mRNA vaccine against respiratory syncytial virus (RSV) in adults older than 60 years of age. “We are pursuing an mRNA RSV vaccine to protect the most vulnerable populations – young children and older adults,” said Stéphane Bancel, Chief Executive Officer of Moderna. “We are studying mRNA-1345 in these populations in an ongoing clinical trial and we look forward to sharing data when available. The Fast Track designation for older adults underscores the urgent need for a vaccine against RSV. With our investments in science and manufacturing, we have taken eleven infectious disease vaccines into human clinical trials. We have accelerated research and development of our infectious disease therapeutic area and we will continue to advance our mRNA vaccines into new areas of high unmet need.” Respiratory syncytial virus is a common respiratory virus that generally causes cold-like symptoms. In the United States and areas with similar climates, RSV infections occur primarily during fall, winter, and spring. Most people recover in a week or two, but RSV can be serious, especially for infants and older adults. RSV is the most common cause of bronchiolitis and pneumonia in children younger than one year of age in the United States and can result in pneumonia and respiratory distress in older adults. According to the U.S. Centers for Disease Control and Prevention, in the United States, RSV leads each year, on average, to approximately 58,000 hospitalizations among children younger than five years old, 177,000 hospitalizations among adults 65 years and older and 14,000 deaths among adults 65 years and older. There is no approved vaccine available today for RSV. Fast Track is designed to facilitate the development and expedite the review of therapies and vaccines for serious conditions and that fill an unmet medical need. Programs with Fast Track designation may benefit from early and frequent communication with the FDA, in addition to a rolling submission of the marketing application. The Company previously received Fast Track designation for its COVID-19 vaccine candidate, Zika vaccine candidate (mRNA-1893), methylmalonic acidemia (MMA) (mRNA-3704) and propionic acidemia (PA) (mRNA-3927) programs. The Phase 1 study of mRNA-1345 to evaluate the tolerability and reactogenicity of mRNA-1345 in younger adults, older adults and children is ongoing. All four cohorts of younger adults (ages 18-49 years) are fully enrolled. Dosing in the older adult cohort (ages 65-79 years) is ongoing. The age range of toddlers in this de-escalation Phase 1 study is 12-59 months. The Company shared the first interim analysis of the Phase 1 study of mRNA-1345, through 1-month post-vaccination, of the younger adult cohorts at its annual Vaccines Day on April 14, 2021. Results showed the vaccine candidate generated a geometric mean rise in neutralizing antibodies relative to baseline of at least 11-fold. The Company also intends to evaluate the potential of combinations of mRNA-1345 with its vaccines against other respiratory pathogens in children and separately in older adults. Moderna owns worldwide commercial rights to mRNA-1345. About mRNA-1345 mRNA-1345 is a vaccine against RSV encoding for a prefusion F glycoprotein, which elicits a superior neutralizing antibody response compared to the postfusion state. RSV is the leading cause of respiratory illness in young children. Older adults (65+) are at high risk for severe RSV infections. mRNA-1345 uses the same lipid nanoparticle (LNP) as Moderna’s authorized COVID-19 vaccine and contains optimized protein and codon sequences....
|
|
Scooped by
Juan Lama
|
Moderna said Monday that its coronavirus vaccine candidate is 94.5% effective in fighting the virus, per an initial analysis released by the company. Why it matters: The Moderna vaccine — alongside Pfizer's similarly effective candidate — provides another dash of hope that the pandemic currently raging across the world could be tamed by next year. The state of play: Moderna's study, done in collaboration with the National Institute of Health, looked at 30,000 participants — with half receiving a placebo. - In 95 cases of COVID-19 that developed among participants, 90 were taking the placebo.
- Of the 11 people who contracted "severe" COVID-19 infections, all were taking a placebo.
- Moderna reports there are no significant safety concerns so far.
- The company also said that the vaccine could be stored at refrigerator temperatures for up to a month — compared to Pfizer's vaccine candidate, which requires ultra-cold conditions.
What they're saying: "It’s extremely good news. If you look at the data, the numbers speak for themselves," said Dr. Anthony Fauci, per the Washington Post. - "I describe myself as a realist, but I’m fundamentally a cautious optimist. I felt we’d likely get something less than this. … I said certainly a 90-plus-percent effective vaccine is possible, but I wasn’t counting on it."
The big picture: The Moderna vaccine was part of the federal government's Operation Warp Speed acceleration project, and the company received about $2.5 billion to back its research and development. - Pfizer, on the other hand, funded its own vaccine research but did commit to an Operation Warp Speed deal to speed potential distribution.
Worth noting: Like Pfizer's announcement last week, Moderna's details on its vaccine candidate came in the form of a press release. - The data has not been peer-reviewed and its effectiveness could change as the study progresses, but Moderna says they plan to submit to a peer-reviewed publication when the study is complete.
- Pfizer CEO Albert Bourla said that his company had avoided such specificity about effectiveness given that the numbers could continue changing as its trial continues.
Moderna's press release (Nov. 16, 2020): https://investors.modernatx.com/news-releases/news-release-details/modernas-covid-19-vaccine-candidate-meets-its-primary-efficacy
|
|
Scooped by
Juan Lama
|
The company said its preliminary test in 8 healthy volunteers was safe. It is on an accelerated timetable to begin a larger human trial soon. The first coronavirus vaccine to be tested in people appears to be safe and able to stimulate an immune response against the virus, its manufacturer, Moderna announced on Monday. The findings are based on results from the first eight people who each received two doses of the vaccine, starting in March. Those people, healthy volunteers, made antibodies that were then tested in human cells in the lab, and were able to stop the virus from replicating — the key requirement for an effective vaccine. The levels of those so-called neutralizing antibodies matched the levels found in patients who had recovered after contracting the virus in the community. The company has said that it is proceeding on an accelerated timetable, with the second phase involving 600 people to begin soon, and a third phase to begin in July involving thousands of healthy people. The Food and Drug Administration gave Moderna the go-ahead for the second phase earlier this month. If those trials go well, a vaccine could become available for widespread use by the end of this year or early 2021, Dr. Tal Zaks, Moderna’s chief medical officer, said in an interview. How many doses might be ready is not clear, but Dr. Zaks said, “We’re doing our best to make it as many millions as possible.”.. Official Moderna's Press Release: https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-positive-interim-phase-1-data-its-mrna-vaccine
|
|
Scooped by
Juan Lama
|
Moderna, Inc., a clinical stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients, today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for its investigational Zika vaccine (mRNA-1893) currently being evaluated in a Phase 1 study for the prevention of Zika virus infection in healthy adults. Fast Track is designed to facilitate the development and expedite the review of therapies and vaccines for serious conditions and fill an unmet medical need. Programs with Fast Track designation may benefit from early and frequent communication with the FDA, in addition to a rolling submission of the marketing application. Moderna previously received Fast Track designation for its methylmalonic acidemia (MMA) program (mRNA-3704), which is now recruiting patients for a Phase 1/2 clinical study. “Protecting against Zika virus transmission, particularly in women during pregnancy, continues to be an area of high unmet need. Fast Track designation supports our belief in the clinical potential of mRNA-1893 and the importance of developing an effective vaccine that can be rapidly developed and deployed,” said Tal Zaks, M.D., Ph.D., chief medical officer at Moderna. “Our Zika program is part of Moderna’s broader commitment to improving global public health through developing mRNA vaccines to prevent the spread of infectious diseases.” mRNA-1893 contains an mRNA sequence encoding for the structural proteins of Zika virus and is designed to cause cells to secrete virus-like particles, mimicking the response of the cell after natural infection. Preclinical data published in The Journal of Infectious Diseases have shown that vaccination with mRNA-1893 protected against transmission of Zika virus during pregnancy in mice.1 mRNA-1893 is currently in a Phase 1 study evaluating safety, pharmacokinetics and pharmacodynamics in healthy volunteers.
|
|
|
Scooped by
Juan Lama
|
Researchers from Karolinska Institutet in Sweden have discovered that the gut microbiome can influence how well people respond to mRNA COVID vaccines. The study, published in the journal npj Biofilms and Microbiomes, suggests that certain bacteria in the gut can enhance the immune response to the vaccine, whereas other bacteria may weaken it. The gut microbiome is the collection of microorganisms that live in our digestive tract. It plays an important role in many aspects of our health, such as digestion, metabolism, and immunity. The researchers wanted to find out if the gut microbiome also affects the response to mRNA COVID vaccines. To do this, the researchers collected stool samples from 68 people living with HIV and 75 healthy individuals before their first mRNA COVID vaccine dose. The researchers analysed the microbiome composition using a technique called 16S rRNA sequencing, which identifies the types and relative abundance of bacteria in the samples. They also measured the levels of antibodies and immune cells that were produced after the vaccination. The results showed that the initial makeup of the gut microbiome could predict the immune response to the vaccine in both groups. They found that a less diverse gut microbiome was associated with a stronger vaccine response, marked by higher levels of spike protein antibodies and spike specific CD4 T-cells. These are key components of the immune system that help to neutralize the virus and prevent severe infection. The researchers also identified specific bacteria that were linked with better or worse vaccine responses. For example, they found that Lactobacillus, Bacteroides, and Lachnospira were associated with higher antibody and immune cell levels, while Cloacibacillus was associated with lower antibody levels. They also found that Bifidobacterium and Faecalibacterium were microbial markers of individuals with higher antibody levels. According to the researchers, the study highlights the significant role of the gut microbiome in the effectiveness of mRNA COVID vaccines. The findings could lead to developing microbiota-focused treatments to enhance vaccine responses, especially in groups that may have weaker responses, such as the elderly or immunocompromised individuals. The potential strategies could include changing the diet or taking probiotics to improve the gut microbiome and immunity, the researchers suggest. The study was conducted in collaboration with the Karolinska University Hospital, and SciLifeLab National Genomics Infrastructure in Stockholm, Sweden. The research was funded by Region Stockholm, the Swedish Research Council, and Physicians Against AIDS. Cited study published in NPJ Biofilms and Microbiomes (Dec. 20, 2023): https://doi.org/10.1038/s41522-023-00461-w
|
|
Scooped by
Juan Lama
|
Katalin Karikó and Drew Weissman laid the groundwork for immunizations that were rolled out during the pandemic at record-breaking speed. This year’s Nobel Prize in Physiology or Medicine has been awarded to biochemist Katalin Karikó and immunologist Drew Weissman for discoveries that enabled the development of mRNA vaccines against COVID-19. The vaccines have been administered more than 13 billion times, saved millions of lives and prevented millions of cases of severe COVID-19, said the Nobel committee. Karikó, who is at Szeged University in Hungary, and Weissman, at the University of Pennsylvania in Philadelphia (UPenn), paved the way for the vaccines’ development by finding a way to deliver genetic material called messenger RNA into cells without triggering an unwanted immune response. They will each receive an equal share of the prize, which totals 11 million Swedish krona (US$1 million). Karikó is the 13th female scientist to win a Nobel Prize in medicine or physiology. She was born in Hungary, and moved to the United States in the 1980s. “Hopefully, this prize will inspire women and immigrants and all of the young ones to persevere and be resilient. That’s what I hope,” she tells Nature. A new chapter The COVID-19 vaccines developed by Moderna and the Pfizer–BioNTech collaboration deliver mRNA that instructs cells to create copies of a protein that is found on SARS-CoV-2 virus particles, called the spike protein. This stimulates the body to make antibodies that target the protein, as well as triggering other immune responses. For decades, mRNA vaccines were considered unfeasible because the injection of mRNA into the body triggered an immune reaction that immediately broke down the mRNA. In the mid-2000s, working at UPenn, Karikó and Weissman demonstrated that swapping one type of molecule in mRNA, called uridine, with a similar one called pseudouridine bypasses the cells’ innate immune defences1. “I’m delighted to see them recognized,” says Robin Shattock, a vaccine scientist at Imperial College London, who has worked on mRNA vaccines. “Their contribution was really fundamental in the success of the COVID-19 vaccines, and I think will underlie RNA technology for some time to come.” “They demonstrated that changing the type of the RNA nucleotides within the vaccine altered the way in which cells see it,” said John Tregoning, a vaccine immunologist at Imperial College London, in a press statement for the UK Science Media Centre. “This increased the amount of vaccine protein made following the injection of the RNA, effectively increasing the efficiency of the vaccination: more response for less RNA.” “This discovery has opened a new chapter for medicine,” said Nobel committee member Qiang Pan Hammarström, an immunologist at the Karolinska Institute in Stockholm, at a press conference after the prize announcement. “Investment in long-term basic research is very important.” Vaccine revolution There are now mRNA vaccines in development for a number of other diseases, including influenza, HIV, malaria and Zika. “It’s really like a revolution starting since the COVID pandemic,” says Rein Verbeke, an mRNA vaccine researcher at the Ghent University in Belgium. He adds that Karikó and Weissman’s contributions were essential to the vaccines’ success during the pandemic, and beyond. “Their part was really crucial to the development of this platform.” A COVID-19 mRNA vaccine containing unmodified RNA, developed by CureVac, based in Tübingen, Germany, was widely seen as a flop after its mediocre performance in clinical trials. Another key component of COVID-19 mRNA vaccines was the lipid nanoparticles (LNPs) that surround the modified RNA and ease its entry into cells. Numerous scientists contributed to the development of LNPs, says Verbeke, and it would have been nice if the Nobel committee had also recognized their contributions to mRNA vaccines. The modification of mRNA and the development of LNPs “were the two major steps that were necessary to have mRNA vaccines working”, he says. Many people were involved in developing LNPs, however, and it would be difficult to single out any one contribution, says Pierre Meulien, who worked on using mRNA to trigger immune responses in the 1990s at Transgène, a small biotech firm near Strasbourg in France. Karikó and Weissman “really created the key to success of the whole enterprise around mRNA vaccines”, he adds. The development of mRNA vaccines and therapeutics is still in its infancy, says Shattock. Scientists and biotechnology companies are busy coming up with new applications for mRNA technology, from cancer treatments to next-generation COVID-19 vaccines. Many teams are also working on improved ways of delivering mRNA. “What we see used today is not what’s going to be used in the future,” he says. “We’re at the beginning of an RNA revolution.” Although COVID-19 jabs put mRNA vaccines on the map, the technology’s impact is likely to reach far and wide, says Karikó. “It is just limitless.” doi: https://doi.org/10.1038/d41586-023-03046-x
|
|
Scooped by
Juan Lama
|
Back in January, Moderna set a planned mpox vaccine on the back burner as the immediate outbreak waned, but now the shot has slid into the priority lane, with entry to the clinic likely a “month or | Back in January, Moderna set a planned mpox vaccine on the back burner as the immediate outbreak waned, but now the shot has slid into the priority lane, with entry to the clinic likely a “month or so” away, according to a top vaccine developer and strategist at the company. Moderna is set to launch a phase 1/2 trial of the shot this summer, Hamilton Bennett, senior director of vaccine access and partnerships at Moderna, said in an interview at the the BIO International Convention. The company had previously teased launching human trials sometime this year. Bennett said the goal is to build a preclinical data package that shows efficacy across orthopoxviruses, which include mpox and smallpox, and then generate "robust" phase 1/2 data to inform dose selection and eventually licensure. She added that the company has met with the U.S. mpox response team a couple of times to say, “this is where we are, these are the barriers that we're seeing.” “They've been incredibly helpful in helping us get access to samples and people and information,” she said. Moderna CEO Stéphane Bancel told Fierce Biotech in January that developing a mpox vaccine was not a high priority as development pressed ahead on more than a dozen unique assets beyond the COVID vaccine that helped make the company a household name. Bennett clarified that he was speaking relative to Moderna’s urgency to develop a COVID-19 vaccine during the pandemic. “I think when Stéphane says it's not a priority, it is not a COVID-like priority,” she said. The upcoming trials are just the latest example of the swiftness of Moderna's mRNA platform. The company announced in May 2022 that preclinical work would begin on an mpox vaccine. But no update had been made on the progress prior to Bancel's comments at the beginning of the year. For Bennett, the development of the shot means more than just the potential for a new product; it’s an opportunity to flex her muscles leading the company’s public health portfolio, a position she’s pivoted to since helping lead development and dissemination of the COVID shot. That new role broadly puts her in charge of coordinating with developing nations to help scale up vaccine-related economic infrastructure and ensuring that Moderna is accountable and its products are available to those nations. Bennett said that mpox is a “perfect example” of some of the barriers the company will face as it develops these products, in part because, as of now, funding for an mpox vaccine is really for a smallpox vaccine. At a grander level, mpox represents a virus that only gained national attention when people outside of Africa began to be infected. Bennett doesn’t want Moderna to be caught on its back foot when addressing diseases of significance, even if they aren’t affecting high-income countries. “Our portfolio in global health is designed to allow those associations to happen because they're not something where we can pick up the phone when the clock starts,” she said. “We need to build those relationships now.”
|
|
Scooped by
Juan Lama
|
Software from Baidu Research yields jabs for COVID that have greater shelf stability and that trigger a larger antibody response in mice than conventionally designed shots. An artificial intelligence (AI) tool that optimizes the gene sequences found in mRNA vaccines could help to create jabs with greater potency and stability that could be deployed across the globe. Developed by scientists at the California division of Baidu Research, an AI company based in Beijing, the software borrows techniques from computational linguistics to design mRNA sequences with more-intricate shapes and structures than those used in current vaccines. This enables the genetic material to persist for longer than usual. The more stable the mRNA that’s delivered to a person’s cells, the more antigens are produced by the protein-making machinery in that person’s body. This, in turn, leads to a rise in protective antibodies, theoretically leaving immunized individuals better equipped to fend off infectious diseases. What’s more, the enhanced structural complexity of the mRNA offers improved protection against vaccine degradation. During the COVID-19 pandemic, mRNA-based shots against the SARS-CoV-2 coronavirus famously had to be transported and kept at temperatures below –15°C to maintain their stability. This limited their distribution in resource-poor regions of the world that lack access to ultracold storage facilities. A more resilient product, optimized by AI, could eliminate the need for cold-chain equipment to handle such jabs. The new methodology is “remarkable”, says Dave Mauger, a computational RNA biologist who previously worked at Moderna in Cambridge, Massachusetts, a maker of mRNA vaccines. “The computational efficiency is really impressive and more sophisticated than anything that has come before.” Linear thinking Vaccine developers already commonly adjust mRNA sequences to align with cells’ preferences for certain genetic instructions over others. This process, known as codon optimization, leads to more-efficient protein production. The Baidu tool takes this a step further, ensuring that the mRNA — usually a single-stranded molecule — loops back on itself to create double-stranded segments that are more rigid (see ‘Design optimization’). Known as LinearDesign, the tool takes just minutes to run on a desktop computer. In validation tests, it has yielded vaccines that, when evaluated in mice, triggered antibody responses up to 128 times greater than those mounted after immunization with more conventional, codon-optimized vaccines. The algorithm also helped to extend the shelf stability of vaccine designs up to sixfold in standard test-tube assays performed at body temperature. “It’s a tremendous improvement,” says Yujian Zhang, former head of mRNA technology at StemiRNA Therapeutics in Shanghai, China, who led the experimental-validation studies. So far, Zhang and his colleagues have tested LinearDesign-enhanced vaccines against only COVID-19 and shingles in mice. But the technique should prove useful when designing mRNA vaccines against any disease, says Liang Huang, a former Baidu scientist who spearheaded the tool’s creation. It should also help in mRNA-based therapeutics, says Huang, who is now a computational biologist at Oregon State University in Corvallis. The researchers reported their findings on 2 May in Nature1. Optimal solutions Already, the tool has been used to optimize at least one authorized vaccine: a COVID-19 shot from StemiRNA, called SW-BIC-213, that won approval for emergency use in Laos late last year. Under a licensing agreement established in 2021, the French pharma giant Sanofi has been using LinearDesign in its own experimental mRNA products, too. Executives at both companies stress that many design features factor into the performance of their vaccine candidates. But LinearDesign is “certainly one type of algorithm that can help with this”, says Sanofi’s Frank DeRosa, head of research and biomarkers at the company’s mRNA Center of Excellence. Another was reported last year. A team led by Rhiju Das, a computational biologist at Stanford School of Medicine in California, demonstrated that even greater protein expression can be eked out of mRNA — in cultured human cells at least — if certain loop patterns are taken out of their strands, even when such changes loosen the overall rigidity of the molecule2. That suggests that alternative algorithms might be preferable, says theoretical chemist Hannah Wayment-Steele, a former member of Das’s team who is now at Brandeis University in Waltham, Massachusetts. Or, it suggests that manual fine-tuning of LinearDesign-optimized mRNA could lead to even better vaccine sequences. But according to David Mathews, a computational RNA biologist at the University of Rochester Medical Center in New York, LinearDesign can do the bulk of the heavy lifting. “It gets people in the right ballpark to start doing any optimization,” he says. Mathews helped develop the algorithm and is a co-founder, along with Huang, of Coderna.ai, a start-up based in Sunnyvale, California, that is developing the software further. Their first task has been updating the platform to account for the types of chemical modification found in most approved and experimental mRNA vaccines; LinearDesign, in its current form, is based on an unmodified mRNA platform that has fallen out of favour among most vaccine developers. A structured approach But mouse studies and cell experiments are one thing. Human trials are another. Given that the immune system has evolved to recognize certain RNA structures as foreign — especially the twisted ladder shapes within many viruses that encode their genomes as double-stranded RNA — some researchers worry that an optimization algorithm such as LinearDesign could end up creating vaccine sequences that spur harmful immune reactions in people. “That’s kind of a liability,” says Anna Blakney, an RNA bioengineer at the University of British Columbia in Vancouver, Canada, who was not involved in the study. Early results from human clinical trials involving StemiRNA’s SW-BIC-213 suggest the extra structure is not a problem, though. In small booster trials reported so far, the shot’s side effects have proved no worse than those reported with other mRNA-based COVID-19 vaccines3. But as Blakney points out: “We’ll learn more about that in the coming years.” Research Cited published in Nature (May 2, 2023): https://doi.org/10.1038/s41586-023-06127-z
|
|
Scooped by
Juan Lama
|
Background: During Late 2022, the SARS-CoV-2 Omicron BA.5 sublineages accounted for most of the sequenced viral genomes worldwide. Bivalent mRNA vaccines contain an ancestral SARS-CoV-2 strain component plus an updated component of the Omicron BA.4/BA.5. Since September 2022, a single bivalent booster dose has been recommended for adults who have completed a primary vaccination series and are at high risk for severe Covid-19 disease. Evidence regarding the effectiveness of the bivalent vaccine in reducing hospitalizations and death due to Covid-19 is warranted.
Methods: This retrospective cohort study included all members of Clalit Health Services, aged ≥65, eligible for a bivalent booster. Hospitalizations and death due to Covid-19 among participants who received the bivalent vaccine were compared with those who did not. A Cox proportional-hazards regression model with time-dependent covariates was used to estimate the association between the bivalent vaccine and Covid-19 outcomes while adjusting for demographic factors and coexisting illnesses.
Findings: A total of 622,701 participants met the eligibility criteria. Of those, 85,314 (14%) received a bivalent-booster during the 70-day study period. Hospitalization due to Covid-19 occurred in 6 bivalent recipients and 297 participants who did not, adjusted hazard ratio (HR): 0.19 (95% CI, 0.08-0.43). Death due to Covid-19 occurred in 1 bivalent recipient and 73 participants who did not, adjusted HR 0.14: (95% CI, 0.02-1.04).
Interpretation: Participants who received the bivalent vaccine had lower hospitalization and mortality rates due to Covid-19 than non-recipients up to 70 days after vaccination.
Funding Information: None. Preprint available at the Lancet: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4314067
|
|
Scooped by
Juan Lama
|
An experimental personalized mRNA vaccine in combination with the immunotherapy Keytruda reduced the risk of recurrence or death from melanoma in patients who had already had surgery, Moderna and Merck said Tuesday. The randomized trial included 157 patients with stage 3 or stage 4 melanoma who had already had surgery. Some patients received nine doses of the experimental cancer vaccine made by Moderna and the immunotherapy made by Merck every three weeks for about a year, and some received only the immunotherapy. Treatment with the experimental vaccine in combination with the immunotherapy reduced the risk of cancer recurrence or death by 44% compared with the immunotherapy alone, the companies said. The preliminary results of a Phase 2b trial were shared in a news release and have not been peer-reviewed or published. The companies said they will publish the full data in the future and share results at an upcoming conference. The companies said they will initiate a Phase 3 study in melanoma patients next year, and will study additional tumor types. “Today’s results are highly encouraging for the field of cancer treatment. mRNA has been transformative for COVID-19, and now, for the first time ever, we have demonstrated the potential for mRNA to have an impact on outcomes in a randomized clinical trial in melanoma,” Stéphane Bancel, chief executive officer for Moderna, said in a news release. Moderna is the maker of one of the mRNA Covid-19 vaccines used in the United States. Moderna and Merck said serious treatment-related adverse events occurred in 14.4% of patients who received the vaccine and immunotherapy in the trial, and in 10% of patients who received only the immunotherapy. Keytruda has some known risks for serious side effects, the companies said. Moderna’s experimental cancer vaccine, mRNA-4157/V940, is designed to prime patients’ immune system to generate a response to their specific tumors. Merck’s Keytruda, which is already used in the treatment of melanoma, stimulates the immune system to attack tumors. According to the American Cancer Society, melanoma accounts for about 1% of all skin cancers, but it causes a majority of skin cancer deaths. It estimates that in 2022, about 100,000 new melanomas will be diagnosed, and more than 7,600 people will die from melanoma. Press release (Dec. 13, 2022): https://investors.modernatx.com/news/news-details/2022/Moderna-and-Merck-Announce-mRNA-4157V940-an-Investigational-Personalized-mRNA-Cancer-Vaccine-in-Combination-with-KEYTRUDAR-pembrolizumab-Met-Primary-Efficacy-Endpoint-in-Phase-2b-KEYNOTE-942-Trial/default.aspx
|
|
Scooped by
Juan Lama
|
Participants in the trial must be between the ages of 18 and 50 and not diagnosed with HIV. Moderna is set to start human trials for its experimental mRNA HIV vaccine as early as Thursday, the first time such a trial has ever been conducted. The big picture: "There's a pressing need for new ways to prevent infection from viruses like HIV and influenza that conventional vaccines have struggled to address and to treat rare genetic diseases and cancers that kill millions each year," Axios' Alison Snyder writes. "Vaccines and therapies based on messenger RNA (mRNA) hold promise as a solution." Details: To participate in the trial, participants have to be between the ages of 18 and 50 and not diagnosed with HIV. Moderna says it is looking for 56 participants. What they're saying: "Even as we have shown that our mRNA-based vaccine can prevent Covid-19, this has encouraged us to pursue more-ambitious development programs within our prophylactic vaccines modality," said Moderna CEO Stéphane Bancel in January, when the company announced the vaccine, per Clinical Trials Arena.
|
|
Scooped by
Juan Lama
|
More people taking Moderna’s coronavirus vaccine reported side effects than those who got the Pfizer shot, according to a recent study. Researchers analyzed reports from more than 3 million vax recipients collected via v-safe, a Centers for Disease Control and Prevention program that tracks reactions to the immunizations. Nearly 70 percent said they had some kind of injection site reaction, like pain or swelling, and half reported general side effects like fatigue or chills, the study found. “A greater percentage of participants who received the Moderna vaccine, compared with the Pfizer-BioNTech vaccine, reported reactogenicity; this pattern was more pronounced after the second dose,” the researchers noted. Of those who got the Moderna shot, 73 percent said they had an injection site reaction, compared with 65 percent of people who got Pfizer’s vaccine, the study found. Nearly 51 percent of Moderna recipients reported experiencing full-body symptoms, compared with 48 percent of those who got the Pfizer shot. The reports came from more than 3.6 million people who got their first dose of a COVID-19 vaccine before Feb. 21 and completed at least one health survey on v-safe within seven days of getting jabbed. The gap widened after the second dose, according to the reports from about 1.9 million people who completed those check-ins after receiving shot No. 2, the study said. Close to 82 percent of people who got their second Moderna vaccine had injection site pain, compared to under 69 percent of those with Pfizer. Overall, 74 percent of Moderna recipients said they experienced full-body symptoms, versus 64 percent of people who got the Pfizer vax. Some 40 percent of people with Moderna specifically reported getting chills, compared with just 22 percent of Pfizer recipients. “Data from millions of v-safe participants indicate that injection site pain is common after both the first and second doses of either mRNA-based vaccine,” the researchers noted. The study was published Monday in the peer-reviewed medical journal JAMA.. Findings published in JAMA (April 5, 2021): https://doi.org/10.1001/jama.2021.5374
|
|
Scooped by
Juan Lama
|
Moderna, the first company to start US clinical trials of a Covid-19 vaccine, on Thursday finished enrolling all 30,000 of its participants. All 30,000 have received their first shot, and most of them have also received the required second shot. The company's president says it's now on track to apply to the US Food and Drug Administration for authorization to put the vaccine on the market in early December "if all the stars align." Dr. Stephen Hoge, Moderna's president, said enrolling 30,000 participants is "just a milestone -- it's not the mission." Half of the participants received the vaccine and half received a placebo, or a shot of saline that does nothing. The participants receive a second shot four weeks later. Moderna is one of four US Phase 3 trials of coronavirus vaccines, each involving tens of thousands of participants. Moderna started its Phase 3 trial July 27, and Pfizer started its trial that evening. AstraZeneca started its US trial August 31 and paused it about a week later when a participant fell ill. Johnson & Johnson started its trial September 23 and paused it less than three weeks later for the same reason. Both of those pauses are still in effect. Pfizer has said it could apply for emergency use authorization after the third week in November. Hoge said three things needs to happen before Moderna applies to the FDA for emergency use authorization. Of the 30,000 participants, 53 need to become sick with Covid-19. The company expects that to happen in the second half of November. The second milestone is that of the 53 participants who become ill with Covid-19, at least 40 of them need to be participants who received the placebo. That would show the vaccine is 75% effective. The third milestone is a requirement by the FDA to ensure that enough time has passed to see if participants develop side effects. The FDA rule is that at least eight weeks must pass after half the participants have received their second shot before a company can apply for emergency use authorization. So far, 25,650 participants have received their second shot, and Hoge said Moderna expects to hit this safety milestone in the second half of November. Thursday, Moderna also released the racial breakdown of its study participants. Of the 30,000 participants, 20% are Latino and 10% are Black. Those are higher than the percentages the company was achieving early in its trial, but still lower than the percentages sought by Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.
|
|
Scooped by
Juan Lama
|
One of the first biotech companies to begin human trials of an experimental vaccine for the coronavirus is now ready to move onto the next phase of testing. On Thursday, Moderna announced that the Food and Drug Administration had cleared its application to proceed to a clinical trial involving about 600 people. “The imminent Phase 2 study start is a crucial step forward,” Stéphane Bancel, Moderna’s chief executive, said in a statement. The main goal of this set of tests is to find out if the vaccine is safe and if positive results from the first few dozen volunteers in the first phase can be replicated in a much larger group. If it is successful, later studies, known as Phase 3 trials, will determine exactly how well the vaccine works. More than a dozen companies, including known vaccine producers like Johnson & Johnson, or Sanofi, are involved in a global race to develop a vaccine to tamp down the highly infectious coronavirus that has killed more than a quarter-million people around the world. Four Chinese companies have started testing their potential vaccines on humans, including CanSino Biologics, which announced the beginning of Phase 2 trials in early April. A few others, such as Pfizer and its German partner, BioNTech, are enrolling volunteers for combined Phase 1 and 2 trials. Dr. Anthony Fauci, the nation’s leading expert on infectious diseases, has suggested that it would still take 12 to 18 months for a vaccine to be widely available to the public. There is no proven treatment, and many researchers and corporations around the world are pursuing remedies in addition to vaccines. Moderna’s vaccine candidate, called mRNA-1273, relies on genetic material known as messenger RNA, which carries the recipe for making proteins to tiny ribosome chefs inside cells. The vaccine is written with a very specific recipe — in this case for making the spike protein of the coronavirus.
|
