AstraZeneca’s COVID-19 Vaccine Shows Its Success: Here’s How It Stacks Up To Others

AstraZeneca announced in a press release Monday that its COVID-19 vaccine has shown positive results in an interim analysis of clinical trial data.

The announcement marks the third vaccine to show high efficacy in late stage trials against the pandemic coronavirus, SARS-CoV-2. Although the efficacy figures for AstraZeneca’s vaccines are not as impressive as those of previous vaccines – mRNA vaccines from Pfizer / BioNTech and Moderna – AstraZeneca offers some 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 data

AstraZeneca has partnered with researchers at the University of Oxford to develop the viral vector vaccine called AZD1222 (also called ChAdOx1 nCoV-19). The vaccine consists of having genetic material encoding the famous SARS-CoV-2 spike protein carried into the body by a relatively benign virus. In this case, the virus is a type of weakened adenovirus – a pathogen that can cause colds and other mild infections in humans and some animals. The adenovirus used is the one that mainly infects chimpanzees. When the adenovirus packet delivers the code for the SARS-CoV-2 spike protein, the immune system can then train to recognize and destroy anything that contains the same spike protein – and that would be all virus particles. SARS-CoV-2, which are studded with advanced proteins.

The AZD1222 results announced today come from a pooled analysis of clinical trials conducted in the UK and Brazil, involving more than 23,000 participants. AstraZeneca’s independent oversight board found that AZD1222 was on average around 70% effective in preventing COVID-19, the disease caused by SARS-CoV-2. The interim analysis was triggered when 131 cases appeared in participants across the trials, who received either two doses of AZD1222 or a comparator vaccine, the meningococcal vaccine MenACWY. The efficacy rate is calculated based on the distribution of these 131 cases in the MenACWY group compared to the AZD1222 group.

But the results were a little more complicated than this simple split. Participants who received AZD1222 received one of two dosing regimens, so the results were further divided. In a diet, participants received a half dose of AZD1222 followed by a booster injection with a full dose. In trials, 2,741 participants received this regimen, and it was found to be around 90% effective in preventing COVID-19.

In the other scheme, participants receiving AZD1222 received two full doses of the vaccine. In other words, they got the same high dosage level in their first shot as they did in their booster shot. In trials, 8,895 participants received this regimen, and it was found to be around 62% effective in preventing COVID-19.

The pooled efficacy data gives an average efficacy of about 70%. This is impressive, given a target of around 50%. However, this is not as high as the amazing mRNA vaccine efficacy results reported in previous weeks. These included 95% efficacy for the Pfizer / BioNTech vaccine and 94.5% efficacy for Moderna.

Unexpected result

AstraZeneca’s better result with the regimen starting with half a dose has already led to some head scratching among experts. More importantly, it’s unclear whether the 90% efficiency result will hold up as AstraZeneca collects more data and conducts additional analysis. We do not yet know how the 131 cases are distributed in the subgroup analyzes. This final efficiency number is very likely to change as more data is collected. But, if this conclusion holds, some experts have already started to speculate on the reasons.

Many believe that this may be due to the packaging of the adenovirus. Although the vaccine aims to stimulate immune responses against the SARS-CoV-2 spike protein carried by the adenovirus, certain immune responses will inevitably attack the adenovirus itself. If the two-dose regimen starts at a high level, it may tip the immunity scales toward a stronger anti-adenovirus response rather than an anti-spike response when the booster is given. This is speculative, however, and understanding what is really going on will require a lot more data.

On a positive note, needing less vaccine in the first dose – if it really ends up being the case – means more people can be vaccinated with the same vaccine-making capacity.

And on another positive note – though very preliminary – Oxford researchers reported that AZD1222 appeared to reduce asymptomatic SARS-CoV-2 infections. The main analysis looked at symptomatic cases of COVID-19, but some trial participants were regularly screened for asymptomatic infection. This finding is particularly disturbing since mRNA vaccine trials have only looked at symptomatic COVID-19 cases. However, the result is extremely preliminary as the researchers did not present any data on this subject.

security

As with mRNA vaccines, AstraZeneca said no serious vaccine-related adverse events “have been confirmed”. In the results of previous trials, mild side effects of AZD1222 were common, including pain, a feeling of fever, chills, muscle pain, headache, and malaise. Some participants received paracetamol (acetaminophen / Tylenol) as a preventative measure to lessen these effects.

If you remember correctly, AstraZeneca has suspended testing at least twice, once in July and again in September, for standard safety reviews. The trials ended in July when a British participant developed neurological symptoms and was subsequently diagnosed with multiple sclerosis. In September, another participant developed symptoms related to transverse myelitis – a condition involving inflammation of the spinal cord that may, in rare cases, be linked to vaccination. Both cases were ultimately considered unrelated to the vaccine itself and trials resumed.

Otherwise, no hospitalizations or serious cases of COVID-19 were reported in the study.

Delivery

A significant advantage of the AstraZeneca adenovirus vaccine is that it is relatively easy to increase production and does not require specialized storage conditions. Adenovirus vectors are more established in the vaccine field than mRNA-based vaccines, which are quite new. The manufacturing capacity to produce large quantities of adenovirus already exists.

AstraZeneca noted in its press release that it is “making rapid progress in manufacturing a capacity of up to 3 billion doses of vaccine in 2021 on an ongoing basis, pending regulatory approval. The vaccine can be stored, transported and handled under normal refrigerated conditions (2-8 degrees Celsius / 36-46 degrees Fahrenheit) for at least six months and administered in existing health facilities. “

MRNA vaccines require cooler storage conditions. In particular, the vaccine from Pfizer and BioNTech requires storage at a troublesome temperature of -70 ° C. In a recent press release, Pfizer noted that the companies “have developed specially designed, temperature-controlled thermal senders using dry ice to maintain temperature conditions of -70 ° C ± 10 ° C. They can be used as temporary storage units for 15 days by filling with dry ice. The vaccine can also be stored under normal conditions refrigerated at 2-8 ° C for five days.

Pfizer and BioNTech aim to have up to 50 million doses of vaccine by 2020 globally and up to 1.3 billion doses by the end of 2021.

Moderna announced in a recent press release that its vaccine remains stable for six months at -20 ° C (-4 ° F), up to 30 days at normal refrigerator temperature (2-8 degrees C or 36-46 degrees F), and up to 12 hours at room temperature. Moderna currently plans to have approximately 20 million doses of mRNA-1273 ready for shipment to the United States in 2020 and to produce an additional 500 million to 1 billion doses globally by 2021.

All three vaccines are now being sent to regulators around the world for clearance. Pfizer submitted its emergency use authorization request to the US Food and Drug Administration on Friday.

Unknown

The three vaccines have yet to release their full data sets, so there remains a lot of uncertainty about the data and analyzes. Efficacy numbers will likely change as trials continue, safety oversight continues, and peer reviewers review the analyzes. Rare side effects are also more likely to appear over time.

Although preliminary studies of the vaccines suggest that they all elicit a variety of immune responses in participants, the duration of protection against any of these vaccines is completely unknown. It is still not clear what levels of immune responses amount to complete protection against infection or serious illness. And in a year-long pandemic with a pathogen completely new to us, it’s impossible to say for sure how long these protective immune responses will remain protective.

Finally, there is no data to date on the protection of vaccines against asymptomatic infections. The prevention of disease – and in particular potentially fatal diseases – is the top priority of these trials. However, the prevention of asymptomatic or mild infections will be essential to end the transmission of SARS-CoV-2 as a whole.