adenovirus

Adenovirus

The Astrazeneca Vaccine Trial

adenovirus
Adenovirus

No hospitalizations or severe cases of COVID-19 in participants treated with AZD1222.

Positive high-level results from an interim analysis of clinical trials of AZD1222 in the UK and Brazil showed the vaccine was highly effective in preventing COVID-19, the primary endpoint, and no hospitalizations or severe cases of the disease were reported in participants receiving the vaccine. There were a total of 131 COVID-19 cases in the interim analysis.

While efficacy was not as high as that reported in the recent Pfizer and Moderna trials, this vaccine has some important advantages with regard to cost and ease of storage. The Oxford vaccine trial used two different dosing regimes. The first and second doses were given one month apart:

  • Two full doses (8,895 participants): 62% efficacy
  • Half dose + full dose (2,741 participants): 90% efficacy
  • Pooled results for both regimes: 70% efficacy

What does efficacy mean? Efficacy is the % reduction in infection between those vaccinated and those receiving a placebo. For 131 infections, a 70% reduction means that around 100 people in the placebo group were infected versus around 30 in the vaccine group.

Why would a half first dose be more effective than a full dose? Scientists aren’t yet sure, but a couple of hypotheses have been proposed:

Vector immunity: the vaccine uses an altered chimpanzee adenovirus (cold virus) to deliver the SARS-CoV-2 spike protein gene into our cells, which then manufactures the spike protein, thus illiciting an immune response. A high initial dose may produce more of a response to the adenovirus and not enough to spike protein. The half dose may hit the sweet spot.

Priming: Professor Andrew Pollard, director of the Oxford vaccine group said, “…by giving a smaller first dose we’re priming the immune system differently, we’re setting it up better to respond.”

Professor Sarah Gilbert, whose team created the vaccine, said, “It could be that by giving a small amount of the vaccine to start with and following up with a bigger amount, that’s a better way of kicking the immune system into action and giving us the strongest immune response.”

Statistical fluke: Given the relatively small numbers in the half-dose group (we don’t yet know how many infections were seen in that group), these results might be imprecise, and the two dosing regimes may actually have more similar efficacy results. As more cases accrue in both groups we can say with more statistical certainty whether they are the same or different.

Despite the somewhat confusing dosing and possible lower efficacy numbers, the results are very welcome for several reasons:

  • This vaccine could do a lot to reduce the burden of COVID-19 infections and deaths globally.
  • There were NO hospitalizations or severe cases in the vaccine group.
  • Suggestive evidence that the vaccine may also prevent asymptomatic infection. During a part of this trial participants were swabbed every week rather than waiting for symptoms.
  • Cheaper: $2.50 per dose compared to $15-25 for Pfizer and Moderna.
  • Storage: The vaccine can be transported and stored at regular refrigerator temperatures (2-8 degrees Celsius/ 36-46 degrees Fahrenheit) for at least six months, making it much easier to distribute around the world.
  • More vaccine may be available sooner. Astrazeneca estimates it will have 200 million doses ready by the end of 2020, and capacity to produce 100-200 million does per month. If the half dose is indeed the preferred first dosing, even more supply will be available.

Given the number of people to vaccinate worldwide to truly beat down this virus, multiple effective vaccines will be key, and the cheaper and easier to distribute the better.

As with the Pfizer and Moderna vaccine, trials are continuing and thus results may change as new information comes in.

Information provided courtesy of dearpandemic.org.

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