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)

Can you still transmit Covid-19 after vaccination?

‘In fact, most vaccines don't fully protect against infection, even if they can block symptoms from appearing. As a result, vaccinated people can unknowingly carry and spread pathogens. Occasionally, they can even start epidemics. 

"Effective" or "sterilising" immunity: There are two main types of immunity you can achieve with vaccines. One is so-called "effective" immunity, which can prevent a pathogen from causing serious disease, but can't stop it from entering the body or making more copies of itself. The other is "sterilising immunity", which can thwart infections entirely, and even prevent asymptomatic cases. The latter is the aspiration of all vaccine research, but surprisingly rarely achieved.

What type of immunity do the Covid-19 vaccines provide? "In a nutshell we don't know, because they’re too new," says Neal. So far, the available Covid-19 vaccines have not been judged primarily on their ability to prevent transmission – though this is now being evaluated as a secondary endpoint for many of them. Instead, their efficacy was assessed by whether they could prevent symptoms from developing. "This means that we set our targets kind of pragmatically," says Danny Altmann, professor of immunology at Imperial College London.’

Read here (BBC, Feb 4, 2021)

How Singapore picked its Covid-19 vaccines

‘Last June, Singapore sealed its first deal to buy Covid-19 vaccines - before any of the more than 200 vaccine candidates had even started their phase three clinical trials. It decided not to wait for the trials, and even paid a premium on the price, in order to secure some early stock of vaccines for people here at high risk, such as healthcare workers and the elderly. That was for the Moderna mRNA vaccine, which has yet to be approved for use here.

‘Singapore signed two more purchase agreements in August - with Sinovac which produces a traditional vaccine, and Pfizer-BioNTech which also uses mRNA. These purchases should provide sufficient vaccines for the entire adult population. But Singapore is buying more. Dr Benjamin Seet, who chaired the panel that picked the vaccines for Singapore, said several late-stage discussions are still ongoing with a handful of other companies - as part of a contingency plan should there be disruptions in the supply of purchased vaccines, delays in the delivery, or even the need for further booster shots.’

Read here (Straits Times, Feb 1, 2021) 

Just like Pfizer, China says vaccines can beat new strains

‘Virologists and vaccine specialists with China’s National Health Commission (NHC) said on Wednesday they had a detailed plan to upgrade homegrown vaccines against Covid-19 to “version 2.0” within two months to stop the spread of new mutant strains found across the United Kingdom and South Africa.

‘The claim coincided with Pfizer’s announcement on Wednesday that its Covid-19 vaccine works against mutated variants found in the UK and South Africa, according to a lab study. China’s claim comes as local firms SinoPharm and Sinovac crank out their Covid-19 shots for mass inoculations.’

Read here (Asia Times, Jan 28, 2021)

Norway moves to calm vaccine anxiety after elderly deaths

‘Health authorities in Norway sought to allay safety concerns raised by the death of some elderly patients after they were vaccinated against Covid-19, saying there’s no evidence of a direct link.

‘The initial reports from Norway raised alarm as the world looks for early signs of potential side effects from the vaccines. Although doctors say it’s possible that vaccine side-effects could aggravate underlying illnesses, they were expecting nursing-home residents to die shortly after being vaccinated because deaths are more common among the frailest and sickest elderly patients.

“Clearly, Covid-19 is far more dangerous to most patients than vaccination,” Steinar Madsen, medical director at the Norwegian Medicines Agency, said by phone on Monday, adding that a connection between the vaccine and the deaths is difficult to prove. “We are not alarmed.”

Read here (Bloomberg, Jan 18, 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)

Pfizer/BioNTech vaccine appears effective against mutation in new coronavirus variants: Study

‘Pfizer Inc and BioNTech’s COVID-19 vaccine appeared to work against a key mutation in the highly transmissible new variants of the coronavirus discovered in the UK and South Africa, according to a laboratory study conducted by the U.S. drugmaker.

‘The not-yet peer reviewed study by Pfizer and scientists from the University of Texas Medical Branch indicated the vaccine was effective in neutralizing virus with the so-called N501Y mutation of the spike protein.’

Read here (Reuters, Jan 7, 2021)

BioNTech warns against delaying second vaccine dose

‘German firm BioNTech warned Tuesday there is no data backing the "safety and efficacy" of delaying the second shot of its Covid-19 vaccine beyond three weeks, as some countries push back the jab to give more people their first dose. BioNTech, which developed the vaccine with US giant Pfizer, said its clinical data showing 95 percent efficacy was based on a two-dose schedule separated by 21 days. "The safety and efficacy of the vaccine has not been evaluated on different dosing schedules," it said. "Although data... demonstrated that there is a partial protection from the vaccine as early as 12 days after the first dose, there is no data to demonstrate that protection after the first dose is sustained after 21 days."

Read here (New Straits Times, Jan 5, 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) 

Covid-19 vaccine developers ask the SEC to help keep the secret of how they set prices

‘When the U.S. government awarded over $10 billion in contracts and advance- purchase commitments to drug companies working on COVID-19 vaccine and treatments, it did not require the recipients of government money to agree to offer their products at fair prices or share intellectual property rights to enable faster production.

‘Now, two of the companies awarded those contracts—Pfizer and Johnson & Johnson—are trying to prevent shareholders from voting on resolutions to require the companies to disclose information about the impact of government funding on vaccine access...

‘The shareholder resolutions, filed by members of the Interfaith Center on Corporate Responsibility (ICCR), a shareholder activism organization, ask those two companies to inform their shareholders how "receipt of public financial support for development and manufacture of products for COVID-19 is being, or will be, taken into account when making decisions that affect access to such products, such as setting prices." Similar resolutions were also filed at Eli Lilly, Gilead, Merck, and Regeneron.

‘Both Pfizer and Johnson & Johnson filed "no action requests" with the Securities and Exchange Commission (SEC) in December, asking the agency to rule that the companies can withhold the proposals from shareholders. Neither company responded to The Daily Poster requests for comment.’

Read here (Newsweek, Jan 2, 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)

Suspicions grow that nanoparticles in Pfizer’s COVID-19 vaccine trigger rare allergic reactions

‘Severe allergy-like reactions in at least eight people who received the COVID-19 vaccine produced by Pfizer and BioNTech over the past 2 weeks may be due to a compound in the packaging of the messenger RNA (mRNA) that forms the vaccine’s main ingredient, scientists say. A similar mRNA vaccine developed by Moderna, which was authorized for emergency use in the United States on Friday, also contains the compound, polyethylene glycol (PEG).

‘PEG has never been used before in an approved vaccine, but it is found in many drugs that have occasionally triggered anaphylaxis—a potentially life-threatening reaction that can cause rashes, a plummeting blood pressure, shortness of breath, and a fast heartbeat. Some allergists and immunologists believe a small number of people previously exposed to PEG may have high levels of antibodies against PEG, putting them at risk of an anaphylactic reaction to the vaccine.’

Read here (Science magazine, Dec 21, 2020)

European Commission embarrassed by Covid-19 vaccine price leak

‘The tweeted information gave the following price per dose for each vaccine maker, in either euros or US dollars according to the respective contract:

1. AstraZeneca: €1.78
2. Johnson & Johnson: US$8.50
3. Sanofi/GlaxoSmithKline: €7.56
4. Pfizer/BioNTech: €12.00
5. Curevac: €10.00
6. Moderna: US$18.00’

Read here (Malay Mail, Dec 18, 2020) 

Whose liability for Pfizer’s vaccine?

‘The well-known The Independent newspaper reports that the United Kingdom Department of Health and Social Care has confirmed that Pfizer required, and has been given, an indemnity by the government, protecting it from legal action if any ill-effects arise from the dispensation of the vaccine.

‘What does this mean? What is the effect in law of such an indemnity? Simply, that the country that provides the indemnity becomes primarily and independently liable if anything goes wrong with the uptake of the vaccine.’

Read here (The Sun Daily, Dec 14, 2020)

WHO to make decisions on Pfizer, Moderna, AstraZeneca COVID-19 vaccines in weeks

‘The World Health Organization expects to make decisions on whether to give emergency use approval to COVID-19 vaccines from Pfizer, Moderna and AstraZeneca in the coming weeks, its chief scientist said on Friday (Dec 11).

‘Soumya Swaminathan said the global health body could decide on Pfizer's vaccine candidate in the next "couple of weeks", and later said it could also review Moderna's and AstraZeneca's candidates in a few weeks.’

Read here (Channel News Asia, Dec 12, 2020)

What an FDA committee weighed in voting for the Pfizer Covid vaccine

‘An all-day hearing of the Food and Drug Administration’s vaccine advisory committee closed, on Thursday evening, with a vote to recommend an Emergency Use Authorization of the Pfizer-BioNTech covid-19 vaccine for people sixteen and older. 

‘The proceedings involved a great deal of data and technical talk, but might be quickly summarized this way: there are things we still do not know about the vaccine, but nothing that we do know looks bad. Indeed, the vaccine looks very, very good. And its known goodness applies to a diverse range of populations, including Black and Latinx and older people. An F.D.A. analysis of the raw data, released earlier this week, confirmed previous reports that the vaccine’s efficacy in preventing disease in trial participants was close to ninety-five per cent. That number held up under questioning from committee members, who represented a range of specialties, from pediatrics to virology, throughout the eight hours of the hearing. 

‘Amid a pandemic—on a day when more than three thousand people in this country were reported to have died from covid-19—that result is far more than it would have been reasonable to hope for even a couple of months ago. As Dr. Doran Fink, of the F.D.A., said in one of the day’s presentations, there is no “adequate, approved, and available alternative.” It was a long day, but a reassuring and even energizing one.’

Read here (The New Yorker, Dec 11, 2020)

Information for UK recipients on Pfizer/BioNTech COVID-19 vaccine: UK government

‘Warnings and precautions: Talk to your doctor, pharmacist or nurse before you are given the vaccine if you have:

• Had a serious allergic reaction to a previous vaccine, medicine or food
• Had any problems following previous administration of COVID-19 mRNA Vaccine BNT162b2 such as allergic reaction or breathing problems
• A severe illness with high fever. However, a mild fever or upper airway infection, like a cold, are not reasons to delay vaccination.
• A weakened immune system, such as due to HIV infection, or are on a medicine that affects your immune system
• A bleeding problem, bruise easily or use a medicine to inhibit blood clotting

‘As with any vaccine, COVID-19 mRNA Vaccine BNT162b2 may not fully protect all those who receive it. No data are currently available in individuals with a weakened immune system or who are taking chronic treatment that suppresses or prevents immune responses.

‘Other medicines and COVID-19 mRNA Vaccine BNT162b2: Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines or have recently received any other vaccine.

‘Pregnancy and breast-feeding: There is currently limited data available on the use of this vaccine in pregnant women. If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before you receive this vaccine. As a precaution, you should avoid becoming pregnant until at least 2 months after the vaccine.’

Click here to read more (UK government, Dec 2020)

Man named William Shakespeare, one of the first to get Pfizer vaccine, sets off pun cascade

‘To be or not to be vaccinated, that is the question. After an 81-year-old named William Shakespeare became the second person in the West to receive the Pfizer-BioNTech coronavirus vaccine in Britain outside clinical trials Tuesday, social media erupted with joy, puns and many quotes from the great British playwright. “They really are prioritising the elderly: this guy is 456,” wrote one user, while the term “Two Gentlemen of Corona,” a play on “The Two Gentlemen of Verona,” swiftly became a top trend in Britain. Others quipped that the first batch of inoculations, part of the first mass coronavirus immunization campaign in the West, marked the “Taming of the Flu.”

Read here (Washington Post, Dec 9, 2020)

People with a history of ‘significant’ allergic reactions shouldn’t have Pfizer jab, UK regulator warns

‘The UK’s Medicines and Healthcare products Regulatory Agency updated its guidance to British health service trusts on who should receive the vaccine. The precautionary advice came after two members of Britain’s National Health Service, who received the vaccine on Tuesday, experienced allergic reactions to the shot. Both are recovering well, according to the national medical director for the NHS.’

Read here (CNBC, Dec 9, 2020)

The science behind an RNA vaccine

‘In just 10 months, a vaccine developed by Pfizer and BioNTech has been approved by Britain for emergency use to prevent Covid-19. Another by Moderna is being evaluated for emergency use authorisation by several regulators, including the United States Food and Drug Administration...

‘This 10-month timeline for vaccines to get from concept to licensing is ground-breaking; most take more than 10 years to reach this stage. There are several other RNA vaccines in the pipeline, including the one our team at Duke-NUS Medical School is working on in partnership with Arcturus Therapeutics. Here is the science behind such vaccines...’

Read here (Straits Times, Dec 7, 2020)