In a bleak year, the past few weeks have brought with them a glut of long-overdue good news. Positive clinical trial results from several vaccine candidates mean that while the pandemic is far from over, it’s now at least possible to see a path back to relative normality.
Here’s everything you need to know about the five frontrunner vaccines that could finally put an end to the coronavirus pandemic for much of the world.
Oxford-AstraZeneca
On November 19, Oxford University published findings from its Phase II/III trials for a Covid-19 vaccine. Combining results from two different dosing regimens, it announced the vaccines had an average effectiveness of 70.4 per cent, which splits into 90 per cent in one dosing regimen, and 62 per cent in the other. This came after clinical trials enrolled over 24,000 participants from across the UK, Brazil and South Africa. Further trials will include 60,000 participants from the United States, Kenya, Japan and India.
Oxford’s vaccine is a partnership between Oxford University and AstraZeneca, a British-Swedish pharmaceutical company based in Cambridge. The vaccine is a genetically altered adenovirus that usually causes the common cold in chimpanzees but has been tweaked to carry the blueprints for part of the coronavirus known as the spike protein. When the vaccine enters the body it uses this genetic code to produce the surface spike protein of the coronavirus, inducing a response that readies the immune system to fight the coronavirus if infected.
Of the big three vaccines – Oxford-AstraZeneca, Moderna and Pfizer/BioNTech – the Oxford-AstraZeneca is currently the cheapest to produce and crucially, it can be stored at a standard temperature between two and eight degrees Celsius in fridges that are found in most GP surgeries and hospitals.
AstraZeneca aims to produce up to three billion doses for the world next year, but when can the UK expect widespread vaccination? So far, the UK government has pre-ordered 100m doses of the Oxford vaccine with Oxford University stating that large-scale manufacturing is ongoing in over 10 countries to support equitable global access. Meanwhile the vaccine has already been referred to the UK’s medical regulatory body, the Medicines and Healthcare products Regulatory Agency (MHRA), for approval. If successful, an NHS rollout would likely happen quickly, with NHS GPs being told they will get 10 days notice before vaccinations in England take place.
For full immunisation, all 68 million UK citizens would need to be administered two doses: a primary dose, then a second administered a few weeks later. A year rollout would be “far too long,” for this says Azeem Majad, professor of primary care and public health at Imperial College London. “Ideally, all vaccines will be done in about four months,” he says. This would require around 17 million vaccinations to be administered per month.
Moderna
On November 16, Massachusetts-based company Moderna published data on its candidate in the race to find a Covid-19 vaccine. For its Phase III test Moderna recruited 30,000 volunteers across the US, with half being given a placebo rather than a vaccine. Analysis of the first 95 cases of Covid-19 detected in participants found that 90 were observed in the placebo group and five in the vaccine group. Based on that data, it demonstrated a 94.5 per cent efficacy.
The Moderna vaccine not only signals a potential return to normal life but a medical breakthrough. Unlike the Oxford-AstraZeneca vaccine, Moderna’s is based on ribonucleic acid (RNA), a molecule similar to DNA that is naturally generated by our bodies.
RNA vaccines work by first introducing an mRNA sequence, a single-stranded messenger molecule which contains the code for cells to produce certain proteins. Cells use this genetic information to produce part of the virus that causes Covid-19 which in turn stimulates an immune response. “It's really just making the chemical signal that instructs a cell to make protein,” says Peter Openshaw, professor of experimental medicine at Imperial College London and member of the UK Coronavirus Immunology Consortium. “It’s straightforward chemistry.”
Moderna is aiming to produce 50m doses by the end of the year. So far, the UK government has secured 5 million doses of the Moderna vaccine and it could be delivered from spring 2021, adding to the UK’s total of 335 million ordered doses. Depending on the amount ordered, its vaccine candidate will cost between $25 (£19) and $37 (£28) per dose.
The potential benefits of mRNA vaccines like Moderna's are great. They can be quicker to produce, more effective than typical vaccines and can be easily reformulated if the virus mutates. Moderna also claims that its vaccine can remain stable at two to eight degrees Celsius, the temperature of a standard home or medical refrigerator, for 30 days. “It's a very flexible, very fast technology that really opens up a whole new field of vaccine development,” says Openshaw. “You can potentially reformulate the same technology to make a vaccine against many other things we'd love to have a vaccine for.”
Pfizer/BioNTech
The New York-based pharmaceutical corporation Pfizer and German company BioNTech were the first to announce a potential vaccine for Covid-19 after their Phase III trial. The trial looked at 94 cases of coronavirus among 43,000 trial participants, with all 94 participants receiving two doses of either a vaccine or the placebo. At seven days after the second dose, Pfizer found that the vaccine was more than 90 per cent effective. Since then, Pfizer announced an updated efficacy rate of 95 per cent beginning 28 days after the first dose. Similarly to Moderna, the Pfizer vaccine is mRNA-based and works well in older, more vulnerable people.
A key problem Pfizer has to overcome is in how its vaccine will be stored and distributed. The Pfizer vaccine needs to be kept at a freezing temperature of -70 degrees Celsius and will degrade in around five days at normal refrigeration temperatures. In the UK, ultra-low temperature freezers are mostly found in hospitals or university facilities, not typical GP surgeries. This also makes distributing the Pfizer vaccine to lower GDP nations much more difficult.
Despite the challenges, Pfizer is pressing on. It aims to produce around 50m doses by the end of 2020 and has already applied to the US Food and Drug Administration for its vaccine to be authorised for emergency use in the US. If successful, Americans could begin receiving doses by mid-December. In the UK, health secretary Matt Hancock has announced that of the 40m Pfizer doses the UK have ordered, 10m will be available by the end of the year.
CanSino Biologics
Named Ad5-nCoV, the Covid-19 vaccine created by Chinese firm CanSino Biologics was the first to be granted approval to be used in people. After Phase II trials of the adenovirus-based vaccine found it to be safe to use on humans on June 25, it was sanctioned for military use for one year.
In recent days, CanSino has been awarded China’s first Covid-19 vaccine patent, but there have been problems along the way. In September, the India newspaper The Economic Times reported that a shipment of vaccines set for Phase III testing in Canada was never approved by the Chinese government, allegedly an act of retaliation after Huawei chief financial officer Meng Wanzhou was arrested by Canadian authorities in 2018.
The vaccine’s success rate is unknown, however, as Chinese vaccine manufacturers are yet to release data from their Phase III tests. Despite this, a ‘booming black market’ for underground and unsanctioned vaccines has started to filter through to the Chinese public. As reported by Bloomberg, doses of a vaccine produced by the Chinese-state owned pharmaceutical company Sinopharm are being sold for as little as $91 (~£61) to well connected members of the Chinese public.
For those hoping for a legitimate way to be vaccinated, Sinopharm is awaiting approval for distribution and if successful, it says it may be possible to produce 1 billion doses in 2021. So far, one million people have taken the vaccine and no serious adverse reactions have been reported.
The Gamaleya Center
Russia’s frontrunner for the Covid-19 vaccine is Gam-COVID-Vac, or ‘Sputnik V’ as it’s been named by the country’s government. The vaccine’s developers, the Russian state-run Gamaleya Center, took a similar approach to Oxford in creating Sputnik V, but instead of using adenovirus vectors from chimpanzees it is based on two human adenovirus vectors.
In August, the Russian government approved usage of the Gam-COVID vaccine, claiming it to be “The first registered vaccine against COVID-19.” This was despite only undergoing a first phase trial of 38 people and without public data to back it up. More recently, Russia has filed applications with the World Health Organization to distribute its vaccine globally. If successful, it could see 200 million doses of Sputnik V making its way to Brazil, Mexico and India.
The vaccine has raised concerns, however. On September 4, the Ministry of Health of the Russian Federation published the findings of its Phase I/II trials. It claimed that “both vaccine formulations were safe and well tolerated” and that all participants produced SARS-CoV-2 antibodies. Three days later, however, almost 40 medical experts from across the globe signed an open letter expressing concerns about these claims, owing to inconsistencies in the success data provided or missing data altogether. “There are a lot of really good scientists and people developing vaccines in Russia,” says Openshaw. “But it's become a little bit political.”
The Russian government is pressing on regardless. Recent press releases from The Gamaleya Center report a vaccine efficacy of over 95 per cent and that each dose will cost just $10 (£7.50) for international markets. No orders of Sputnik V have come from the UK so far but to date, 50m have been ordered from Brazil, 100m from India, 25m from Egypt and 32m from Mexico.
This article was originally published by WIRED UK
