Could mRNA make us superhuman?

‘Until recently most people had never even heard of mRNA vaccines. Now scientists believe they may be the key to solving a wealth of health problems...

‘The theory behind the mRNA vaccine was pioneered by University of Pennsylvania scientists Katalin Karikó and Drew Weissman, who both recently received the 2021 Lasker Award, America's top biomedical research prize. Even in 2019, however, mainstream mRNA vaccines were believed to be at least five years away. The pandemic fast-forwarded this field of medicine by half a decade. Kathryn Whitehead, an associate professor of chemical engineering and biomedical engineering at Carnegie Mellon University, and a key collaborator of Weissman and Karikó admits, "there weren't many people in the mRNA therapeutics world who would have imagined 95% initial efficacy rates in this emergency scenario".

‘But now, the possibilities are seemingly endless. Or, as Blakney puts it: "Now it's like, OK, so it's worked for a viral glycoprotein, what other vaccines can we make with it? And what can we do beyond that?"... 

‘All this raises the question: could mRNA therapeutics give us almost superhuman immunity? Already Covid-19 mRNA vaccines lead some people to produce very high levels of antibodies, able to neutralise several variants of Covid-19 at once. 

‘There's also the potential to mix various mRNA vaccines together into a single health booster vaccine, which could ward off cancers and viruses at the same time. While it's just speculation at present, Fu says, "you could take a whole bunch of different flavours… a cocktail of mRNAs that make different proteins selective for your particular need." Both Moderna and Novavax already have combined Covid-19 and flu vaccines in development.’

Read here (BBC, Nov 23, 2021)

‘Maybe the coronavirus was lower-hanging fruit’

‘Emerging mRNA technology proved excellent for COVID vaccines. BioNTech’s founders preview what that could mean for cancer and other mysteries...

‘The fact that mRNA technology had never delivered an authorized therapy before the coronavirus pandemic could tell us one of two things. Perhaps synthetic mRNA is like a miraculous key that humankind pulled out of our pockets in this pandemic, but it was so perfectly shaped for the coronavirus that we shouldn’t expect it to unlock other scientific mysteries any time soon.

‘Or perhaps mRNA is merely in the first chapter of a more extraordinary story. This month, BioNTech announced that it had initiated Phase 2 trials of personalized cancer vaccines for patients with colorectal cancer. It is working on other personalized cancer vaccines and exploring possible therapies for malaria using a version of the mRNA technology that had its breakout moment in 2020.’

Read here (The Atlantic, Oct 18, 2021)

Official: Chinese vaccines’ effectiveness low

‘In a rare admission of the weakness of Chinese coronavirus vaccines, the country’s top disease control official says their effectiveness is low and the government is considering mixing them to give them a boost. Chinese vaccines “don’t have very high protection rates,” said the director of the China Centers for Disease Control, Gao Fu, at a conference Saturday in the southwestern city of Chengdu.

‘Beijing has distributed hundreds of millions of doses in other countries while also trying to promote doubt about the effectiveness of Western vaccines. “It’s now under formal consideration whether we should use different vaccines from different technical lines for the immunization process,” Gao said.’

Read here (AP News, Apr 11, 2021)

Q&A: BioNTech vaccine is only ‘mRNA 1.0’. This is just the beginning, say co-founders

‘The successful development of mRNA vaccines for Covid-19 is ‘transformational’ and opens the doors to new types of vaccines for other infectious diseases as well as cancer, according to Dr Özlem Türeci and Dr Uğur Şahin, the co-founders of Germany’s BioNTech.’

Read here (Horizon, Apr 8, 2021)

Kati Kariko helped shield the world from the coronavirus

‘Collaborating with devoted colleagues, Dr. Kariko laid the groundwork for the mRNA vaccines turning the tide of the pandemic...

‘Now Katalin Kariko, 66, known to colleagues as Kati, has emerged as one of the heroes of Covid-19 vaccine development. Her work, with her close collaborator, Dr. Drew Weissman of the University of Pennsylvania, laid the foundation for the stunningly successful vaccines made by Pfizer-BioNTech and Moderna.

‘For her entire career, Dr. Kariko has focused on messenger RNA, or mRNA — the genetic script that carries DNA instructions to each cell’s protein-making machinery. She was convinced mRNA could be used to instruct cells to make their own medicines, including vaccines.

‘But for many years her career at the University of Pennsylvania was fragile. She migrated from lab to lab, relying on one senior scientist after another to take her in. She never made more than $60,000 a year.’

Read here (New York Times, Apr 7, 2021)

How mRNA technology could change the world

‘mRNA’s story likely will not end with COVID-19: Its potential stretches far beyond this pandemic...

‘But mRNA’s story likely will not end with COVID-19: Its potential stretches far beyond this pandemic. This year, a team at Yale patented a similar RNA-based technology to vaccinate against malaria, perhaps the world’s most devastating disease. Because mRNA is so easy to edit, Pfizer says that it is planning to use it against seasonal flu, which mutates constantly and kills hundreds of thousands of people around the world every year. The company that partnered with Pfizer last year, BioNTech, is developing individualized therapies that would create on-demand proteins associated with specific tumors to teach the body to fight off advanced cancer. In mouse trials, synthetic-mRNA therapies have been shown to slow and reverse the effects of multiple sclerosis. “I’m fully convinced now even more than before that mRNA can be broadly transformational,” Özlem Türeci, BioNTech’s chief medical officer, told me. “In principle, everything you can do with protein can be substituted by mRNA”.’

Read here (The Atlantic, Mar 29, 2021)

BioNTech and Fosun Pharma form Covid-19 vaccine strategic alliance in China

• BioNTech and Fosun Pharma will jointly conduct clinical trials of BNT162 in China, leveraging BioNTech’s proprietary mRNA vaccine technology and Fosun Pharma’s clinical development and commercialization capabilities in China
• Fosun Pharma will commercialize the vaccine in China upon regulatory approval, with BioNTech retaining full rights to develop and commercialize the vaccine in the rest of the world
• Fosun Pharma will pay BioNTech up to USD 135M (EUR 120M) in upfront and potential future investment and milestone payments; the two companies will share future gross profits from the sale of the vaccine in China

Read here (BioNTech press statement, Mar 16, 2021)

Finding an ultimate vaccine to fight the mutating “emperor” virus

‘We are commenting on the shocking CNN website report (March 2), headlined “All our recent progress with COVID-19 could be wiped out by variants, CDC director says”. The first two paragraphs (below) are enough to sum up the CNN report: “The US is at risk of losing all its recent gains in the battle against COVID-19 as highly contagious variants take advantage of Americans getting lax with safety measures... “Please hear me clearly: At this level of cases with variants spreading, we stand to completely lose the hard-earned ground we have gained,” said Dr Rochelle Walensky, director of the US centers for Disease Control and Prevention (CDC).”...

‘With new variants, serious doubts are suggested by the CNN report on whether this “vaccine” [mRNA], the first in the global market, would work, even if safety factor is put aside. Nevertheless, there are safe and workable vaccines, using tried and tested technologies like using inactivated or attenuated virus from nature to stimulate the body to produce anti-body response. Even the adenovirus viral vector technology, tried and tested for Ebola, appears to be safer than mRNA.

‘There are also safe and good alternatives, like the anti-viral “broad spectrum” drug Ivermectin, which can destroy the new variants. In the meantime, it is vital that we improve our body immunity against COVID-19 by taking Vitamin C with zinc, Vitamin D, minerals and trace elements needed, explore proven traditional and complimentary medicines, and maintain established standard operating procedures (SOPs) of physical distancing, wearing surgical masks and personal hygiene in public places.’

Read here (Focus Malaysia, Mar 4, 2021)

How Covid-19 vaccine efforts could help defeat other diseases

• A proposed way of immunizing against malaria uses an RNA-based approach similar to COVID-19 vaccines.
• ‘Viral vector’ methods used to stem the pandemic could also yield vaccines for other purposes.
• COVID-19 vaccination achievements could be applied to diseases that kill millions of people annually.

Read here (World Economic Forum, Mar 4, 2021)

Synthetic mRNA Covid vaccines: A risk-benefit analysis

‘With a “vaccine” based on untested technology, and safety trials still ongoing, is it safe to take the shot? And does it even work? And does a disease with an IFR of 0.2% even justify that risk?’

Read here (Off Guardian, Feb 22, 2021)

Experts answer the biggest Covid vaccine questions

‘The lack of informed messaging from the Trump administration, combined with the range of different COVID vaccines, the emergence of new coronavirus variants, and inconsistent state and municipal rollout plans, have caused confusion and driven vaccine hesitancy. Scientific American asked Namandjé Bumpus, a pharmacologist at Johns Hopkins Medicine in Baltimore, and Ashley Lauren St. John, an immunologist at Duke-NUS Medical School in Singapore to answer some of the biggest questions about the currently available COVID vaccines:

• Should you get an authorized COVID vaccine now if you are eligible?
• Should you get vaccinated if you have already had COVID?
• How should you interpret vaccine efficacy—what does “95 percent efficacy” or “66 percent efficacy” even mean?
• If you get the vaccine and still get infected, does the vaccine still make a difference? 
• Will it prevent severe disease or death?
• Do the vaccines protect against the new virus variants, including those first identified in the U.K., South Africa and Brazil?
• What is the difference between mRNA and viral vector vaccines?
• Is there a “best” vaccine?
• Will the vaccine protect you from giving the virus to others?
• Will the vaccine’s effectiveness “wear off” over time?
• Should you be worried about allergic reactions to the vaccine?
• How can you ensure you’re getting a legitimate, authorized vaccine?

Read here (Scientific American, Feb 19, 2021)

Pfizer withdraws vaccine application in India [after failing to present needed information to experts]

‘Pfizer Inc says it has withdrawn its application for emergency use of its COVID-19 vaccine in India. The company said Friday that it participated in a meeting of experts of the drug regulator on Feb. 3. Based on the deliberation of that meeting and “our understanding of additional information that the regulator may need, the company has decided to withdraw its application at this time,” it said in a statement.

‘The company was the first to approach the Indian regulator in December for its messenger RNA vaccine that it has developed with Germany’s BioNTech. They were closely followed by applications for two other vaccines --- a version of the AstraZeneca made by Serum Institute of India and another by Indian company Bharat Biotech -- which eventually got the nod for emergency use on Jan. 3. However, India’s Health Ministry has said that Pfizer hadn’t made its presentation to experts who needed to clear the vaccine, before the regulator could green-light its use in India.’

Read here (The Independent, Feb 6, 2021)

Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine

‘It is important to note that all the severe Covid-19 cases were in the placebo group, which suggests that mRNA-1273 is likely to have an effect on preventing severe illness, which is the major cause of health care utilization, complications, and death. The finding of fewer occurrences of symptomatic SARS-CoV-2 infection after a single dose of mRNA-1273 is encouraging; however, the trial was not designed to evaluate the efficacy of a single dose, and additional evaluation is warranted.

‘Overall, the safety of the mRNA-1273 vaccine regimen and platform is reassuring; no unexpected patterns of concern were identified. The reactogenicity associated with immunization with mRNA-1273 in this trial is similar to that in the phase 1 data reported previously. Overall, the local reactions to vaccination were mild; however, moderate-to-severe systemic side effects, such as fatigue, myalgia, arthralgia, and headache, were noted in about 50% of participants in the mRNA-1273 group after the second dose. These side effects were transient, starting about 15 hours after vaccination and resolving in most participants by day 2, without sequelae.’

Read here (New England Journal of Medicine, Feb 4, 2020)

A new vaccine to battle Covid-19 -- NEJM editorial

‘That the mRNA-1273 Covid-19 and the BNT162b2 Covid-19 vaccines protect with near-identical 94 to 95% vaccine efficacies — and that both vaccines were developed and tested in less than a year — are extraordinary scientific and medical triumphs. This happened because the scientific community was prepared from years of technology development for other vaccines, such as those against HIV, influenza, respiratory syncytial virus, and Zika, and because clinical trials consortia were established that rapidly carried out Covid-19 efficacy trials. If mRNA-LNP vaccines significantly contribute to control of the pandemic, mRNA technology has the potential to radically change vaccine design for future viral outbreaks.

‘Although the Covid-19 pandemic is currently raging, the prospects for control of this and future pandemics are bright. The recent FDA issuance of EUAs for these extraordinarily protective vaccines provide us with much-needed hope at a time when so many are suffering. The next challenge is to get these and the next Covid-19 vaccines to the people most at risk as quickly as possible.’

Read here (New England Journal of Medicine, Feb 4, 2020)

How to redesign Covid vaccines so they protect against variants

‘Some aspiring vaccine makers have had their eye on the threat that escape variants might pose from the start. A team at Gritstone Oncology decided to focus on this potential problem by designing a vaccine that targets multiple sites on several viral proteins, in contrast to first-generation shots that target only the spike protein, says Andrew Allen, president of the company in Emeryville, California. The hope is that the vaccine, which should soon start clinical trials, will make it difficult for the virus to evade immunity because many genetic changes would be necessary for it to do so. “You can either play whack-a-mole and chase the variants, or you can try to get ahead of them,” Allen says.

‘Because updating the construction of existing vaccines is relatively simple, a new RNA vaccine could be designed and manufactured for clinical testing within six weeks, Weissman estimates. But that is only the beginning. “Mass-producing a vaccine is hard. To start all over again will be hard,” says Offit. Some researchers are expecting periodic updates to coronavirus vaccines, as with flu, to become a way of life. “This is not unusual,” says Stanley Plotkin, a consultant who advises companies on vaccines. But it could mean that worries over supply chains and logistics will continue for some time.’

Read here (Nature, Jan 29, 2021)

Chinese health experts call to suspend Pfizer's mRNA vaccine for elderly after Norwegian deaths

‘Chinese health experts called on Norway and other countries to suspend the use of mRNA-based COVID-19 vaccines produced by companies such as Pfizer, especially among elderly people, due to the vaccines' safety uncertainties following the deaths of 23 elderly Norwegian people who received the vaccine. 

‘The new mRNA vaccine was developed in haste and had never been used on a large scale for the prevention of infectious disease, and its safety had not been confirmed for large-scale use in humans, a Chinese immunologist said. The death incidents in Norway also proved that the mRNA COVID-19 vaccines' efficacy was not as good as expected, experts said. 

‘As of Thursday, Norway has reported 23 deaths in connection with vaccination."So far, 13 of these have been assessed. Common side effects may have contributed to a severe course in frail elderly people," the Norwegian Medicines Agency said on its website. All the deaths have occurred in frail, elderly patients in nursing homes. All are over 80 years old and some of them over 90, Norwegian media NRK reported.’

Read here (Global Times, Jan 15, 2021)

Peter Doshi: Pfizer and Moderna’s “95% effective” vaccines—we need more details and the raw data

Peter Doshi: Pfizer and Moderna’s “95% effective” vaccines—we need more details and the raw data 

‘Five weeks ago, when I raised questions about the results of Pfizer’s and Moderna’s covid-19 vaccine trials, all that was in the public domain were the study protocols and a few press releases. Today, two journal publications and around 400 pages of summary data are available in the form of multiple reports presented by and to the FDA prior to the agency’s emergency authorization of each company’s mRNA vaccine. While some of the additional details are reassuring, some are not. Here I outline new concerns about the trustworthiness and meaningfulness of the reported efficacy results...’

Read here (BMJ, Jan 4, 2021) 

Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine (Pfizer clinical trial)

BACKGROUND: ‘Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently.’

METHODS: ‘In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety.’

RESULTS: ‘A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups.’

CONCLUSIONS: ‘A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728. opens in new tab.)’

Read here (New England Journal of Medicine, Dec 31. 2020)

Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine

‘This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2.

‘The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline... 

‘The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427. opens in new tab.)’

Read here (New England Journal of Medicine, Dec 30, 2020)

Breaking down Moderna’s Covid-19 patent pledge: Why did they do it?

‘Last month, Moderna Therapeutics, one of the global leaders in the race to produce a COVID-19 vaccine using mRNA, made the following statement regarding enforcement of its patents: “We feel a special obligation under the current circumstances to use our resources to bring this pandemic to an end as quickly as possible. Accordingly, while the pandemic continues, Moderna will not enforce our COVID-19 related patents against those making vaccines intended to combat the pandemic. Further, to eliminate any perceived IP barriers to vaccine development during the pandemic period, upon request we are also willing to license our intellectual property for COVID-19 vaccines to others for the post pandemic period.”

‘This post examines why Moderna made this patent pledge by examining its mRNA technology, go-to-market status, patent landscape, and market position.’

Read here (IP Watchdog, Nov 11, 2020)