Sat. Oct 1st, 2022
AstraZeneca's COVID-19 vaccine shows success: Here's how it compares to others

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

The announcement marks the third vaccine to show strong efficacy in late-stage trials against the pandemic coronavirus, SARS-CoV-2. While AstraZeneca’s efficacy rates are not as impressively high as its vaccines – mRNA vaccines from Pfizer/BioNTech and Moderna – AstraZeneca does offer some advantages over those vaccines.

All in all, the news adds to rising optimism that effective vaccines could end the global crisis in the coming year.

The vaccine and its data

AstraZeneca collaborated with researchers from the University of Oxford to develop the viral vector-based vaccine AZD1222 (also called ChAdOx1 nCoV-19). The vaccine involves having genetic material encoding the infamous SARS-CoV-2 spike protein that is introduced 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 is a virus that primarily infects chimpanzees. When the adenovirus package delivers the code for the SARS-CoV-2 spike protein, the immune system can train itself to recognize and destroy anything with the same spike protein — and that would be all SARS-CoV-2 viral particles, those studded with spike 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 review board 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 131 cases emerged in study participants who received either two doses of AZD1222 or a comparator vaccine, the meningococcal vaccine MenACWY. The efficacy rate is calculated based on how those 131 cases split into the MenACWY group versus the AZD1222 group.

But the results were a little more complicated than that simple split. Participants who received AZD1222 were given one of two dosing schedules, so the results split further. In one regimen, participants received a half-dose of AZD1222 followed by a full-dose booster injection. In the studies, 2,741 participants were given this regimen and it was found to be about 90 percent effective in preventing COVID-19.

In the other regimen, participants who received AZD1222 received two full doses of the vaccine. In other words, they received the same high dose level with their first injection as they had with their booster injection. In the studies, 8,895 participants were given this regimen and it was found to be about 62 percent effective in preventing COVID-19.

The pooled efficacy data yield the average efficacy around 70 percent. This is impressive, given a target of about 50 percent. However, it is not as high as the astounding results of mRNA vaccine efficacy reported in previous weeks. Those include 95 percent efficacy for the vaccine from Pfizer/BioNTech and 94.5 percent efficacy for Moderna’s.

Unexpected result

AstraZeneca’s better outcome with the half-dose regimen has already caused head scratching among experts. Most importantly, it’s unclear whether the 90 percent efficacy result will hold up as AstraZeneca collects more data and conducts further analyses. We do not yet know how the 131 cases are distributed in the subgroup analyses. That final efficacy figure will most likely change as more data is collected. But if that finding holds up, some experts have already begun to speculate as to why.

Many think it has to do with the packaging of the adenovirus. While the vaccine is intended to elicit immune responses against the SARS-CoV-2 spike protein carried by the adenovirus, some immune responses will inevitably attack the adenovirus itself. Starting the two-dose regimen high may tip the immunity scales toward a stronger anti-adenovirus response rather than an anti-peak response when the booster injection is administered. However, this is speculative and to understand what is really happening, much more data is needed.

On the plus side, less vaccine is needed in the first dose — if that’s really the case — means more people can be vaccinated with the same amount of vaccine production capacity.

And yet another positive, albeit very tentative observation, 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 study participants were regularly screened for asymptomatic infection. This finding raises eyebrows in particular, as the mRNA vaccine trials looked at only symptomatic COVID-19 cases. However, the finding is extremely preliminary as the researchers have not presented any data on it.

Safety

As with the mRNA vaccines, AstraZeneca said no serious side effects related to the vaccine “have been confirmed.” In previous study results, mild side effects of AZD1222 were common, including pain, fever, chills, muscle aches, headache, and malaise. Some participants were given acetaminophen (acetaminophen/Tylenol) preventively to reduce these effects.

If you recall, AstraZeneca has paused its trials at least twice, once in July and another in September, for standard safety assessments. The trials ended in July when a British participant showed neurological symptoms and was later diagnosed with multiple sclerosis. In September, another participant developed symptoms consistent with transverse myelitis — a condition involving inflammation of the spinal cord that, in rare cases, may be related to vaccination. Both cases were ultimately declared unrelated to the vaccine itself and trials resumed.

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

Delivery

An important advantage of AstraZeneca’s adenovirus vaccine is that it is relatively easy to scale up production and does not require special storage conditions. Adenovirus vectors are more established in the vaccine arena, compared to mRNA-based vaccines, which are brand new. Production capacity already exists to produce large quantities of adenovirus.

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

The mRNA vaccines require cooler storage conditions. Most notably, the vaccine from Pfizer and BioNTech has to be stored at a tricky -70°C. In a recent press release, Pfizer emphasized that the companies have “developed specially designed, temperature-controlled thermal dispatchers that use dry ice to maintain temperatures of -70°C ± 10°C. They can be used as temporary storage units for 15 days by refilling them with dry ice.” The vaccine can be stored for a further five days at normal refrigerated conditions of 2-8°C.

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

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

All three vaccines are now going to regulators around the world for authorization. Pfizer filed Friday for an Emergency Use Authorization from the U.S. Food and Drug Administration.

strangers

All three vaccines have yet to have their full datasets published, so there remains a lot of uncertainty about the data and analyses. Efficacy rates are likely to change as studies continue, safety monitoring lengthens, and peer reviewers look at the analyses. Rare side effects also become more common as time goes on.

While preliminary studies on the vaccines suggested that they all elicit a variety of immune responses in participants, it’s completely unknown how long any protection against any of these vaccines can last. It is still unclear what levels of immune responses correspond to complete protection against infection or serious disease. And in a one-year-old pandemic with a pathogen completely new to us, it’s impossible to say for sure how long those protective immune responses will remain protective.

Finally, there is as yet no data on how well the vaccines protect against asymptomatic infections. The prevention of disease – and in particular life-threatening diseases – has the highest priority in these studies. However, preventing asymptomatic or mild infections will be key to ending SARS-CoV-2 transmission in general.

By akfire1

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