Enlarge /. Vials in front of the logo of UK biopharmaceutical company AstraZeneca can be seen in this creative photo taken on November 18, 2020.
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AstraZeneca announced in a press release on Monday that its COVID-19 vaccine had shown positive results in an interim analysis of clinical trial data.
The announcement marks the third vaccine that shows strong efficacy against the pandemic coronavirus SARS-CoV-2 in late-stage studies. While AstraZeneca's vaccine effectiveness numbers aren't as impressively high as those of its previous vaccines – mRNA vaccines from Pfizer / BioNTech and Moderna – AstraZeneca offers several advantages over these vaccines.
Overall, the news adds to the growing optimism that effective vaccines could end the global crisis in the coming year.
The vaccine and its dates
AstraZeneca worked with researchers from Oxford University to develop the viral vector-based vaccine AZD1222 (also called ChAdOx1 nCoV-19). The vaccine contains genetic material that codes for the infamous SARS-CoV-2 spike protein, which is transmitted into the body by a relatively benign virus. In this case, the virus is a weakened type of adenovirus – a pathogen that can cause colds and other mild infections in humans and some animals. The adenovirus used mainly infects chimpanzees. If the adenovirus package provides the code for the SARS-CoV-2 spike protein, the immune system can train itself to recognize and destroy everything with the same spike protein – and that would be all SARS-CoV-2 virus particles occupied with spike proteins.
The AZD1222 results announced today come from a pooled analysis of clinical trials conducted in the UK and Brazil involving over 23,000 participants. AstraZeneca's independent monitoring body found that AZD1222 was, on average, about 70 percent effective in preventing COVID-19, the disease caused by SARS-CoV-2. The interim analysis was triggered when there were 131 cases among study participants who received either two doses of AZD1222 or a comparator vaccine, the meningococcal vaccine MenACWY. The effectiveness rate is calculated based on how those 131 cases were divided into the MenACWY group versus the AZD1222 group.
However, the results were a little more complicated than this simple breakdown. Participants who received AZD1222 received one of two dosing regimens so the results were further divided. In one regimen, participants received half a dose of AZD1222 followed by a booster shot of a full dose. In the studies, 2,741 participants received this regimen, and it appeared to be about 90 percent effective in preventing COVID-19.
In the other therapy, participants who received AZD1222 received two full doses of the vaccine. In other words, they got the same high dose on their first shot as they did on their booster shot. In the studies, 8,895 participants received this regimen, and it appeared 62 percent effective in preventing COVID-19.
The pooled effectiveness data show an average effectiveness of around 70 percent. This is impressive with a goal of around 50 percent. However, it is not quite as high as the impressive mRNA vaccine efficacy results published in the past few weeks. These included a 95 percent effectiveness for the Pfizer / BioNTech vaccine and a 94.5 percent effectiveness for the Moderna vaccine.
AstraZeneca's better result when the regimen starts with half a dose has already caused head scratches among experts. Most importantly, it is unclear whether the 90 percent efficacy result will hold as AstraZeneca collects more data and performs further analysis. We do not yet know how the 131 cases in the subgroup analyzes are divided. This final effectiveness number is very likely to change as more data is collected. However, if this statement is true, then some experts have already begun to speculate as to why.
Some think it might be because of the adenovirus packaging. Although the vaccine is aimed at triggering immune responses against the adenovirus-borne SARS-CoV-2 spike protein, some immune responses inevitably attack the adenovirus itself. If the two-dose regimen starts high, it can cause the immunity scale to target a stronger anti-adenovirus response than an anti-spike response when the booster shot is fired. This is speculative, however, and a lot more data is required to understand what is actually happening.
On the positive side, fewer vaccines are needed in the first dose – when it actually is – that more people can be vaccinated with the same amount of vaccine manufacturing capacity.
And once again positively – albeit very provisionally – the Oxford researchers reported that AZD1222 appeared to reduce asymptomatic infections with SARS-CoV-2. The primary analysis looked at symptomatic cases of COVID-19, but some participants in the study were regularly checked for asymptomatic infections. This finding raises eyebrows in particular, as only symptomatic COVID-19 cases were examined in the mRNA vaccine studies. However, the finding is extremely preliminary as the researchers did not provide any data on it.
As with the mRNA vaccines, AstraZeneca said that no serious adverse events related to the vaccine were "confirmed". In previous experimental results, mild side effects of AZD1222 were common, including pain, fever, chills, muscle pain, headache, and malaise. Some participants received paracetamol (Paracetamol / Tylenol) preventively to reduce these effects.
If you recall, AstraZeneca paused its attempts at least twice, once in July and once in September, to perform standard security checks. The studies were halted in July when a British participant showed neurological symptoms and was later diagnosed with multiple sclerosis. In September, another participant developed symptoms related to transverse myelitis – a disease associated with inflammation of the spinal cord that, in rare cases, can be linked to vaccination. Both cases were eventually declared independent of the vaccine itself and the trials continued.
Otherwise, no hospital admissions or severe cases of COVID-19 were reported in the study.
A key advantage of AstraZeneca's adenovirus vaccine is that production can be scaled up relatively easily and no special storage conditions are required. Adenovirus vectors are more established in the vaccine space than mRNA-based vaccines, which are brand new. There is already production capacity for the production of large quantities of adenoviruses.
AstraZeneca stated in its press release that it is “making rapid progress in manufacturing, with a capacity of up to 3 billion doses of the vaccine in 2021 on a rolling basis pending regulatory approval. The vaccine can be stored, transported, and handled and administered in existing health facilities for a minimum of six months under normal refrigeration conditions (2 to 8 degrees Celsius). "
The mRNA vaccines require cooler storage conditions. In particular, the Pfizer and BioNTech vaccine must be stored at -70 ° C. In a recent press release, Pfizer emphasized that the companies “have developed specially designed temperature controlled thermal shippers that use dry ice to maintain temperature conditions of -70 ° C ± 10 ° C. They can be used as temporary storage for 15 days by topping up dry ice. “The vaccine can also be stored for five days in normal refrigerated conditions of 2 to 8 ° C.
Pfizer and BioNTech are targeting up to 50 million vaccine doses worldwide by 2020 and up to 1.3 billion doses by the end of 2021.
Moderna recently announced in a press release that its vaccine is stable for six months at -20 ° C (-4 ° F), for up to 30 days at normal refrigerator temperature (2-8 ° C or 36-46 ° F) 12 hours at room temperature. Moderna currently plans to ship approximately 20 million doses of mRNA-1273 in the United States by 2020 and to produce an additional 500 million to 1 billion doses worldwide by 2021.
All three vaccines are now being forwarded to regulatory authorities for global approval. Pfizer filed its application for emergency clearance with the U.S. Food and Drug Administration on Friday.
All three vaccines have yet to publish their full datasets, so there is still great uncertainty about the data and analysis. Efficacy numbers are likely to change as studies continue, safety surveillance lengthens, and peer reviewers review the analyzes. Rare side effects also become more common over time.
While preliminary studies of the vaccines indicated that they all elicit a variety of immune responses in participants, it is completely unknown how long protection from any of these vaccines can last. It is still unclear which immune responses correspond to complete protection against infection or serious illness. And in a one-year pandemic with a pathogen that is completely new to us, it is impossible to say with certainty how long these protective immune responses will remain protective.
Finally, there is no data so far on how well the vaccines protect against asymptomatic infections. The prevention of diseases – and especially life-threatening diseases – is a top priority in these studies. However, preventing asymptomatic or mild infections is key to ending the transmission of SARS-CoV-2 altogether.