LIVE BLOG: R&D response to COVID-19 pandemic (archived)

US biotech Moderna announced it has completed manufacturing of clinical trial material of a vaccine designed to protect against the SARS-CoV-2 variant known as B.1.351, which was first identified in South Africa, and has shipped doses to the US National Institutes of Health (NIH) for a phase I clinical trial, to be led and funded by NIH.

While initial data confirms the approved Moderna COVID-19 vaccine works against B.1.351, the company is evaluating using booster doses of vaccine to increase neutralising immunity against this and other variants of concern.

“We look forward to beginning the clinical study of our variant booster and are grateful for the NIH’s continued collaboration,” said Stéphane Bancel, CEO of Moderna. “Leveraging the flexibility of our mRNA platform, we are moving quickly to test updates to the vaccines that address emerging variants of the virus in the clinic. Moderna is committed to making as many updates to our vaccine as necessary until the pandemic is under control.”

At the same time, Moderna said it is making new capital investments to increase manufacturing capacity at its own and partner’s facilities. This will increase 2022 manufacturing capacity to approximately 1.4 billion doses. Given the six to nine months needed to add capacity and further time to get regulatory approval, it is estimated it will be 12 months before the additional production is available.

“We are investing in this additional capacity to help us increase production and allow for flexibility in manufacturing potential vaccine boosters to address emerging variants of the virus,” said Bancel.

Moderna is also increasing its base plan for 2021 manufacturing from 600 million doses to 700 million doses, and is exploring other approaches to potentially improve throughput, working to further optimise operations to potentially deliver up to one billion doses in 2021.

To date, the company has shipped approximately 60 million doses globally including approximately 55 million doses shipped to the US government and four million doses from its ex-US supply chain.

Scientists from around the world published more than 87,000 papers about the SARS-CoV-2 coronavirus between the start of the COVID-19 pandemic and October 2020, a new analysis shows.

Even given the context of the pandemic, researchers were surprised by the huge number of studies produced on the subject in such a short time.

"It is an astonishing number of publications, it may be unprecedented in the history of science," said Caroline Wagner, associate professor at Ohio State University, who is co-author the research, published in Scientometrics.

The analysis, carried out with Xiaojing Cai at Zhejiang University in China, and Caroline Fry at the University of Hawaii, found 4,875 COVID-19 related articles were published between January and mid-April 2020. That rose to 44,013 by mid-July and 87,515 by the start of October.

Wagner compared the amount of journal papers on the coronavirus to the attention given to nanotechnology, which was one of the hottest areas in science during the 1990s. It took more than 19 years to go from 4,000 to 90,000 scientific articles on that topic. "Coronavirus research reached that level in about five months," she said.

This new study was an update of an earlier one published in July 2020, which found that China and the US led the world in coronavirus research during the early months of the pandemic.

The new study shows China's contributions dropped off significantly after infection rates in the country fell. From Jan. 1 to April 8, Chinese scientists were involved in 47% of all worldwide publications on the coronavirus. That dropped to only 16% from July 13 to October 5.

Similar results were found in other countries when infection levels dropped among their populations.

"At the beginning of the pandemic, governments flooded scientists with funding for COVID research, probably because they wanted to look like they were responding," Wagner said. "It may be that when the threat went down, so did the funding."

In China, the work was also slowed by a government requirement that officials approve all articles related to COVID-19, according to Wagner.

The rate of international collaborations also continued to drop, the study found. Part of the reason was the practical barrier that travel bans made it impossible for researchers to meet.

But there may have also been a political component, Wagner said, particularly in US-China collaborations. The Chinese government's requirement of study review is one factor, but in addition, the US government has been putting Chinese researchers in the US under scrutiny, which may have led some scientists to forgo partnerships.

"We need to figure out a way to restart these collaborations as we move into the post-COVID period," Wagner said. "International cooperation is crucial for the scientific enterprise."

COVID-19 vaccination has been linked to a substantial reduction in the risk of being admitted to hospital with COVID-19, according to the first population-level study of a live vaccination programme.

The data cover 1.1 million of 5.4 million people in Scotland  to have received the first dose of either the Pfizer/BioNTech or AstraZeneca vaccines, confirming previous results about vaccine efficacy from clinical trials.

By the fourth week after receiving the initial dose, the Pfizer/BioNTech reduced hospitalisation by 85% and AstraZeneca by 94%, respectively.

The finding is significant because there were not many older people in the AstraZeneca phase III clinical trial. That led Germany to say this vaccine should not be given to the over 65s, but now the data indicate AstraZeneca may be more protective than the Pfizer/BioNTech vaccine in the older age groups.

Among those aged 80 years and over - one of the highest risk groups - vaccination was associated with an 81 per cent reduction in hospital admissions in the fourth week, when the results for both vaccines were combined.

The level of protection seen after a single dose is also an important corroboration of the UK’s controversial policy of maximising population level protection by giving as many first doses to as many people as possible. That is at odds with what it says on the labels of the vaccines, which is that the second dose should be three weeks after the first for Pfizer/BioNTech and four weeks for AstraZeneca   

As part of the EAVE II project, which uses patient data to track the pandemic and the vaccine roll out in real time, researchers from the universities of Edinburgh, Strathclyde, Aberdeen, Glasgow and St Andrew’s and Public Health Scotland analysed a dataset covering the entire Scottish population of 5.4 million.

Data on vaccine effect was gathered between 8 December and 15 February. During this period, 1.14 million vaccines were administered and 21% of the Scottish population had received a first dose.

The Pfizer/BioNTech vaccine had been received by some 650,000 people and 490,000 had had the AstraZeneca vaccine.

Researchers analysed data for every week during this period, including GP records on vaccination, hospital admissions, death registrations and laboratory test results, and compared the outcomes of those who had received their first dose with those who had not.

Dynamic modelling of the movements of the proteins in the spike structure via which SARS-CoV-2 enters and infects human cells, has led to the identification of a 'hinge' mechanism, that gives the spike of the virus purchase to hook onto the cell.

The modelling also pinpointed changes in the shape of the virus that then enable it to fuse with the host cell membrane and enter the hooked cell.

The research, led by Warwick University as part of Eutopia, an alliance of six universities funded by the EU Erasmus+ programme, involved simulating movements in the structure of 287 proteins of the Covid-19 virus, in an effort to identify drug targets.

In a paper published in Scientific Reports, the team of physicists and life scientists have made their data, movies and structural information, detailing how the proteins move and how they deform, publicly accessible.

“Knowing how this mechanism works is one way in which you can stop the virus, and in our study we are the first to see the detailed movement of opening,” said lead author, Rudolf Roemer, professor in the department of physics at Warwick University, who did the work while on a sabbatical at CY Cergy-Paris Université. “Now that you know what the range of this movement is, you can figure out what can block it,” he said.

Pfizer and BioNTech announced results from a laboratory study that provides additional data on the capability of blood samples from individuals immunised with their COVID-19 vaccine to neutralise variants of the SARS-CoV-2 that have the South African mutations in the spike protein.

This study, which builds on previous work, was conducted by Pfizer and the University of Texas Medical Branch and investigated the full set of South African variant (also known as B.1.351) spike mutations.

Three genetically engineered recombinant viruses were produced, one with the full set of spike mutations found in the South African variant and the other two with subsets of these mutations. These viruses were tested against blood from 15 participants who were immunized in the previously reported phase II trial.

Although the results indicated a reduction in neutralisation of virus with all the South African variant spike glycoprotein mutations, all the blood samples neutralised all the viruses tested.

The two companies said there is also no clinical evidence to date that the South African variant virus escapes the protection provided by their vaccine. However, Pfizer and BioNTech are taking steps and making investments to be in a position to develop and seek authorisation for an updated mRNA vaccine or booster once a variant that significantly reduces the protection from the vaccine is identified.

The Commission has announced a European bio-defence preparedness plan against COVID-19 variants, which will bring together researchers, biotech companies, manufacturers and public authorities in the EU and globally, to detect new variants of SARS-CoV-2 that could reduce the efficacy of vaccines.

There will be incentives to develop new and adapted vaccines, speed up regulatory approval and support scale up of manufacturing capacities.

Key actions will include developing tests for new variants; supporting viral genome sequencing in member states with at least €75 million in EU funding to reach the target of sequencing 5% of viral samples from positive tests to help identify variants, monitor their spread and assess their impact on transmissibility; and speeding up research and data exchange on variants with €150 million funding.

US biotech Moderna said the European Commission is buying an additional 150 million doses of its COVID-19 vaccine, bring confirmed orders to 310 million doses for delivery in 2021. The latest doses are scheduled to be delivered in the third and fourth quarter of the year.

Under the terms of the agreement, the Commission has an option to purchase an additional 150 million doses for delivery in 2022.

Stéphane Bancel, CEO of Moderna, said, “The European Commission is in discussions with us on how to prepare for 2022, including addressing potential variants [of the virus].”

Pfizer and BioNTech have announced an agreement with the European Commission to supply an additional 200 million doses of their COVID-19 vaccine Comirnaty, to the EU.

This new agreement is in addition to the 300 million doses that have already been committed to the EU in 2021 under the first supply agreement signed last year. The additional 200 million doses are expected to be delivered in 2021, with an estimated 75 million to be supplied in the second quarter.

The total number of doses to be delivered to the EU member states by the end of 2021 is now 500 million, with the potential to increase to 600 million based on an option granted in the new agreement.

Albert Bourla, CEO of Pfizer said, “With this new agreement with the European Commission, we now expect to deliver enough doses to vaccinate at least 250 million Europeans before the end of the year.”

“We have taken additional steps to expand our manufacturing capacity to two billion doses in 2021,” said Ugur Sahin CEO of BioNTech. “We will initiate production at our Marburg facility this month.”

The UK government has awarded funding to extend its support for COVID-19 clinical trials to the earliest phase I studies, making it possible to rapidly progress new therapies through all stages of development in the country.

Four therapies have so far been selected for phase I development. Future treatments will be selected by the UK COVID-19 therapeutics advisory panel, which is open to receiving proposals from academic groups and companies.

Currently, the government is funding phase II and III studies, including the large scale Recovery trial, which is testing existing drugs in hospitalised COVID-19 patients. The randomised study, which recruited its 36,000 patient last week, has found two therapies, dexamethasone and tocilizumab, that are effective, and shown that four suggested treatments are not.

Phase I trials are the essential first step that ensures treatments are safe. The government backing is for Agile, a phase I/IIa clinical trial platform run in a collaboration between Liverpool, Lancaster and Southampton universities, and other external partners

The design of the platform means that multiple potential treatments can be evaluated in parallel and testing can be completed in months rather than years.

Patients in the early stages of COVID-19 infection will be recruited to Agile from the community, in addition to patients who have been hospitalised with COVID-19. Drugs that show a signal of benefit in Agile will be considered for advancement into later phase clinical trials.

Policymakers should learn lessons from the success of research and development (R&D) in responding to COVID-19, to rethink approaches to tackling healthcare and environmental challenges, according to a new study.

Economists from Bath University and the International Monetary Fund examined the drivers of innovation in global pharmaceutical R&D, finding research carried out by the industry typically follows a law of diminishing effort. This means that while the global death burden of a disease doubles, the intensity of research effort rises by only 50%.

However, the scientific response to COVID-19 is a major exception, with seven to twenty times more COVID-19 clinical trials than this historical relationship would imply.

During the pandemic, global pharmaceutical R&D, as measured by the number of clinical trials, has scaled up by 38%, with only a modest reduction of research on other diseases.

But much of this response occurred via public research institutions, which account for 70% of all COVID-19 trials globally.

The researchers say their findings suggest global pharmaceutical innovation has room to grow, but that government incentives and support from public research institutions should play a crucial role in supplementing the private research.

Patrick Gaule, senior lecturer in economics at Bath University and co-author of the study said, “The rate and direction of innovation is shaped by incentives and government policy actions. Traditionally, economists have emphasised the market size as an important driver for innovation - the greater the private demand for an innovation, the more innovation we should expect in that domain.”

"However, this may not be sufficient by itself to encourage innovation to address the deadliest diseases - from coronary heart disease to lung cancer, or indeed other major challenges facing humanity, namely climate change.”

Instead, the response to COVID-19 suggests that scaling up global innovation in the future may require moves to complement the market size effect with early-stage incentives that harness the power of public research institutions and non-monetary incentives, for example altruism, Gaule said.