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Oxford-AstraZeneca’s Covid-19 Vaccine Up to 90% Effective

posted by Jason Kottke   Nov 23, 2020

Preliminary results from the trials of the Covid-19 vaccine jointly developed by the University of Oxford and AstraZeneca indicate that the vaccine’s overall efficacy is 70% but that a regimen that calls for a lower first dose is 90% effective.

The preliminary results on the AstraZeneca vaccine were based on a total of 131 Covid-19 cases in a study involving 11,363 participants. The findings were perplexing. Two full doses of the vaccine appeared to be only 62% effective at preventing disease, while a half dose, followed by a full dose, was about 90% effective. That latter analysis was conducted on a small subset of the study participants, only 2,741.

Hopefully more study will be done on that dosage question. From the AP:

“The report that an initial half-dose is better than a full dose seems counterintuitive for those of us thinking of vaccines as normal drugs: With drugs, we expect that higher doses have bigger effects, and more side-effects,” he said. “But the immune system does not work like that.”

The seemingly lower efficacy comes with some perhaps significant benefits: this vaccine is cheaper to produce and doesn’t require any special refrigeration.

The vaccine can be transported under “normal refrigerated conditions” of 2 to 8 degrees Celsius (36 to 46 degrees Fahrenheit), AstraZeneca said. By comparison, Pfizer plans to distribute its vaccine using specially designed “thermal shippers” that use dry ice to maintain temperatures of minus-70 degrees Celsius (minus-94 degrees Fahrenheit).

The Pfizer and Moderna vaccines were pretty similar in many respects and this one seems quite different. These results were just released a few hours ago, so it will be interesting to follow the debate and expert commentary on this. Stay tuned…

Update: This is amazing: the seemingly more effective 1/2 dose + full dose regimen was a mistake.

Around the time when Astra was initiating its partnership with Oxford at the end of April, university researchers were administering doses to trial participants in Britain.

They soon noticed expected side effects such as fatigue, headaches or arm aches were milder than expected, he said.

“So we went back and checked … and we found out that they had underpredicted the dose of the vaccine by half,” said Pangalos.

A far smaller number of participants was given the initial half-dose, so more research will need to be done to determine if this mistake will be added to the long list of scientific discoveries made because of errors. There’s a good piece in Nature that talks about what we know and don’t know about the vaccine results so far along with some informed speculation.

But, if the differences are bona fide, researchers are eager to understand why. “I don’t think it’s an anomaly,” says Katie Ewer, an immunologist at Oxford’s Jenner Institute who is working on the vaccine. “I’m keen to get into the lab and start thinking about how we address that question.” She has two leading theories for why a lower first dose might have led to better protection against COVID. It’s possible that lower doses of vaccine do a better job at stimulating the subset of immune cells called T cells that support the production of antibodies, she says.

Another potential explanation is the immune system’s response against the chimpanzee virus. The vaccine triggers an immune response not only to the SARS-CoV-2 spike protein, but also to components of the viral vector. It’s possible that the full first dose blunted this reaction, says Ewer. She plans to look at antibody responses against the chimpanzee virus to help address this question.

Update: A short thread by Dr. Natalie Dean, which leads with “AstraZeneca/Oxford get a poor grade for transparency and rigor when it comes to the vaccine trial results they have reported”.

Initial Data Shows Covid-19 Vaccine Is More than 90% Effective

posted by Jason Kottke   Nov 09, 2020

In a press release (and not a paper in a peer-reviewed journal) based on a preliminary outside review of data from its phase 3 trial, Pfizer says its Covid-19 vaccine was more than 90% effective in preventing the disease.

The company said that the analysis found that the vaccine was more than 90 percent effective in preventing the disease among trial volunteers who had no evidence of prior coronavirus infection. If the results hold up, that level of protection would put it on par with highly effective childhood vaccines for diseases such as measles. No serious safety concerns have been observed, the company said.

I really hope this analysis holds up when more data from the study is released:

The data released by Pfizer Monday was delivered in a news release, not a peer-reviewed medical journal. It is not conclusive evidence that the vaccine is safe and effective, and the initial finding of more than 90 percent efficacy could change as the trial goes on.

The world, and the United States, could really really use some good news like this about the pandemic.

Update: Here’s Pfizer’s press release. And a thread from Dr. Natalie Dean on how she is interpreting this news (“Celebrate, but let the process play out over time as intended.”)

Pfizer’s first analysis was planned for 32 events, which they pushed back after discussions with FDA. But by the time they analyzed the data, 94 had accrued. This shows how quickly trials can generate results when placed in hotspots (and how much transmission is ongoing!).

These vaccines are tested until a certain number of infections happen. So you have this interesting paradoxical situation where if a potential vaccine is more successful at curbing infection, the longer it takes for the study to conclude. You get a better vaccine but wait longer for it. Countering that are the rising transmission counts in the US — more community transmission will get you to the target number of infections more quickly.

Update: From virologist Dr. Florian Krammer, a thread about what Pfizer and other companies will be looking for in terms of the efficacy of vaccines in a number of different situations. Overall, he is optimistic about these preliminary results. And here’s a FAQ about the vaccine from the NY Times.

Another open question is whether children will get protection from the vaccine. The trial run by Pfizer and BioNTech initially was open to people 18 or older, but in September they began including teenagers as young as 16. Last month, they launched a new trial on children as young as 12 and plan to work their way to younger ages.

Update: A very simplified explanation of Pfizer’s RNA-based vaccine.