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

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”.