November 23rd 2020 was a day that lightened the gloom of the second national lockdown and brought new hope for a global victory against the Covid-19 pandemic. Phase III clinical trial results of the Covid-19 vaccine jointly developed by the University of Oxford and AstraZeneca confirmed the effectiveness of the vaccine in preventing infection.

The Oxford-AstraZeneca vaccine, developed by a team led by Professor Andrew Pollard and Professor Sarah Gilbert, is a type of adenovirus vectored vaccine. Their team has previously attempted to use this technique to produce vaccines against other coronaviruses, such as Middle East Respiratory Syndrome (MERS).

This vaccine aims to familiarise human immune systems with the spike protein on the surface of Covid-19. The spike protein gives the virus its “crown” shape, and helps the virus contact and infect host cells. The vaccine contains genetically edited chimpanzee adenovirus, which consequently loses its ability to infect human cells and acquires the ability to express Covid-19 spike proteins on its surface. Just as pilots need to go through thousands of hours of training on flight simulators, the genetically edited adenovirus provides the human immune system with a simulator environment that trains immune cells in recognizing and fighting Covid-19. The edited adenoviruses are stable, and thus can be stored at fridge temperature. This significantly lowers the cost of its production and transportation, and AstraZeneca is determined not to pursue profit in making this vaccine but rather to focus on providing it to low-income and middle-income nations.

The clinical trials that started in April and lasted until November provided unexpected good news. In phase III trials, among the test group, around 3000 volunteers were administered a half-dose shot and a standard-dose shot four weeks later, while around 9000 volunteers were administered two standard-dose shots across four weeks. Of all volunteers, 131 later became infected with Covid-19, among whom only 30 came from the test group. This means that the vast majority of those who became infected with Covid-19 had not received the vaccine. Further, only 3 of these 30 patients were from the half-dose/standard-dose treatment group. Scientists thus concluded that a half dose plus a standard dose yields 90% efficacy, two standard doses yield 62% efficacy, and overall, the vaccine provides 70% protection. All statistics are higher than the 50% benchmark for a vaccine to be considered effective. In addition, data from 24,000 volunteers across three trial phases, different regions, and different age groups proved the safety of this vaccine, showing that adverse responses are rarely observed. This meant that the vaccine was now ready to proceed to regulator review, and a step closer to mass manufacture and roll-out.

The Oxford-AstraZeneca vaccine seems promising in its affordability, effectiveness, and safety. The UK government has pre-ordered 100 million doses of this vaccine, many more than other existing vaccine variants. As of November 27th, AstraZeneca had submitted the preliminary data from all clinical trials of the vaccine to the UK Medicines and Healthcare Products Regulatory Agency (MHRA) for emergency approval. The MHRA is reviewing the data to reach conclusions about the vaccine’s efficacy and safety. However, scepticism developed as the results underwent peer review.

One major concern regarded the high efficacy of one half-dose shot followed by one standard-dose shot. From the discovery of antibiotic penicillin to the painkiller ibuprofen, scientific breakthroughs are often driven by chance. It turns out that this treatment group existed not by design, but by the fluctuation of vaccine dosage during its early manufacture – some of the vaccine prototypes contained less viral vectors than expected. This issue was immediately reported to regulators in the early stages of phase III trials, but both regulators and scientists agreed to continue with the trials. Scientists at Oxford and AstraZeneca are studying the reasons behind the higher efficacy to supplement existing data. Experimental bias has been ruled out as the cause, for though the U.S. reported that the half-dose vaccines were only administered to volunteers younger than 55, results from phase I and II trials show that the vaccine effectively elicits an immune response in volunteers of all age groups. The mainstream hypothesis states that the half-dose vaccines simulate better the process by which immune systems encounter coronaviruses.

Lately, the new mutation of the coronavirus, medically termed N501Y, has become the centre of attention. It has aroused great agitation around the world, raising worries about the effectiveness of vaccines developed before its most recent mutation. Moncef Slaoui, the scientific head of U.S. Operation Warp Seed, an organization that promotes Covid-19 vaccine development, has explained that all vaccine candidates trigger diverse immune responses, and it is thus unlikely that a mutation disrupts all of these immune pathways. Scientists at the University of Texas medical branch reported that antibodies triggered by existing vaccines also neutralize the mutant strand viruses.

In general, most parties are optimistic about the approval and application of the vaccine shortly. Professor Helen Fletcher from the London School of Hygiene and Tropical Medicine claims that “the safety data we have seen has been very robust”. Immunologist Peter Openshaw at Imperial College London has also assured the public that it is promising that the Oxford-AstraZeneca vaccine will soon join the other two vaccines – Pfizer/BioNTech and Moderna – in saving lives from the pandemic. Recently, senior Whitehall officials revealed that the vaccine is likely to be approved before the arrival of the New Year. According to the latest news from The Telegraph on December 27th, the vaccine will be rolled out from January 4th, 2021.

Once the vaccine is authorized, the Joint Committee on Vaccination and Immunisation will decide upon the details of the vaccine roll-out scheme. Former director of immunisation at the Department of Health Professor David Salisbury suggests that there is a trade-off in deciding whether to use the Oxford-AstraZeneca vaccine or the Pfizer/BioNTech vaccine. While the latter yields stronger and more consistent protection, the former costs less and is easier to transport, which contributes to wider immunisation. He proposed to provide more vulnerable groups with the Pfizer/BioNTech vaccine, while the younger population might receive the Oxford-AstraZeneca vaccine.

As more regions including Oxfordshire entered Tier 4 on Boxing Day, it is important to remain cautious as well as optimistic. Though the urgent need for social distancing inevitably reduces the usual hustle and bustle of the holiday season, the public will have to patiently wait and hope for the approval and application of this new vaccine with great potential.

Yexuan Zhu

Aside from science, Yexuan enjoys a wide variety of arts, visual, acoustic, or theatrical. She loves to write about arts and life sciences and she hopes to help make them more accessible and approachable.