With the just released AstraZeneca news, we now have positive results from Phase 3 clinical trials of three different SARS-CoV-2 vaccines.
This is more good news on the vaccine front.
Top line results from this vaccine are available from the press release. They tested two different dosing regimens:
Half dose followed by a full dose at least a month later was 90% effective
Full dose followed by a full dose at least a month later was 62% effective
The 70% effective number that you’re seeing in some news articles is combined analysis from both doses.
AstraZeneca released the full protocol here.
This vaccine protocol monitors for asymptomatic infection with blood testing, which is different than the Pfizer and Moderna trials that are only evaluating symptomatic infection.
Let’s take a look at some of the important questions about this news.
What’s different about this vaccine?
The AstraZeneca vaccine works in a completely different mechanism than the Pfizer and Moderna vaccines.
The other two were mRNA vaccines, which doses you with genetic instructions to make a viral protein that you can mount an immune response against.
This vaccine uses a type of virus called an adenovirus that has been modified to include genetic material from SARS-CoV-2 so that your body mounts an immune response.
As you might imagine, having a viral vector creates two major buckets of theoretical concerns:
Efficacy concerns: viral vectors can induce an immune response to the vector itself and not to the COVID protein that it’s engineered to carry.
Safety concerns: i.e. side effects. These concerns have to do with the immune response induced by the viral vector can have unintended consequences.
The potential for side effects from an adenovirus vector will raise alarm bells for anyone familiar with the history of gene therapy. About 20 years ago, a young boy named Jesse Gelsinger died after getting a therapy for a genetic disorder delivered with an adenovirus vector. (This isn’t a gene therapy trial, it’s a vaccine, so the circumstances are really different here.)
You may remember that this vaccine’s clinical trial was previously put on hold because of reports of vaccine-induced transverse myelitis, a serious neurological disorder that can be life threatening.
Despite these concerns, the initial reports seem really promising. The vaccine doesn’t seem to have its efficacy reduced by the viral vector and there wasn’t a signal for serious side effects.
Why would anyone give this vaccine over the others?
This vaccine is more stable and doesn’t require the same level of refrigeration that the Moderna and Pfizer vaccines do. So it might be easier to distribute.
The other point is that the numbers from this vaccine include asymptomatic infection according to their report.
We don’t know many details about the Pfizer and Moderna with regards to asymptomatic infection. Just like with this vaccine, we’re waiting on the full dataset of those so that we can fully scrutinize the numbers.
It’s also interesting to note that the half dose-full dose combo provided better results in this trial than the full dose-full dose combo. There are all kinds of theoretical mechanisms that immunologists are tossing around:
Some experts had feared that if viral-vectored vaccines required a priming and then a boosting dose, the immune system might recognize the viral vector — in this case the adenovirus — and shut down the immune response before the vaccine has a chance to boost the response to the spike protein.
Fauci said the smaller initial dose may “tickle” the immune system enough to generate T cells, but not trigger development of antibodies that might work to suppress the response to the booster shot.
So what’s the bottom line here?
We’re in a great spot vaccine-wise.
Unless there’s something unreliable with these numbers, some combination of the vaccines that we have should help us end the pandemic.
I’m skeptical that there’s any real pharma funny business going on here. I think that the numbers will check out when they’re fully evaluated in depth.
These companies have too much to lose reputation-wise from misleading vaccine reports. The FDA has too much to lose by approving a vaccine that doesn’t meet efficacy and safety muster.
So if there really is this degree of difference in our final efficacy numbers - over 90% for Pfizer/Moderna and around 70% for AstraZeneca - it seems unlikely that the AstraZeneca vaccine will end up getting approved for US use.
And while I’m not dismissing the enormous challenge of effective distribution, now it feels like the end of the pandemic will be vaccine-facilitated and happen within the next year.
I think that we’ll all feel better after the first few million doses of approved vaccines have been out there so we can get a better sense of the rare side effects, but seeing the initial reports from these three is a huge step forward.
It’s a remarkable accomplishment to go from identification of a novel virus to completed trials of 3 successful vaccines within 10 months. We can all be thankful this year for the human ingenuity that accomplished this work.
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