Researchers in the U.K. on Monday delivered the broadest evidence yet that an experimental vaccine can cause people to generate an immune response against the novel coronavirus.
Study results, published in the journal The Lancet, come from a large Phase 1 trial testing a vaccine developed by the University of Oxford in 1,077 healthy volunteers in the U.K. The data show that the shot spurs two different types of immune responses, an encouraging sign indicating it’s working as intended. Inoculation led to the development of infection-fighting antibodies, but also of immune cells called T cells that are thought to be important in building protective immunity.
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The vaccine doesn’t appear to be significantly superior to candidates being developed by other groups, but it’s not yet clear how protective each vaccine in human testing is and how long any protection might last. Comparing vaccine results, especially at this early stage, is also challenging because each developer is measuring immune responses in slightly different ways.
“There is still a long way to go,” said Sarah Gilbert, the lead researcher of the vaccine development program and a professor at Oxford, on a call with reporters Monday. “The difficulty that we and other vaccine developers face [is] we don’t know how strong that immune response needs to be.”
Oxford’s vaccine, which was licensed to British drugmaker AstraZeneca, was tested in healthy adults between 18 and 55 years old. Five hundred and forty-three volunteers were given the experimental vaccine, now dubbed AZD1222, while another 534 receive a meningococcal vaccine as a control. Ten trial participants got a second, “booster” shot of AZD1222.
A month after vaccination, researchers found antibodies capable of neutralizing the coronavirus in 32 of 35 volunteers who got a single shot and were measured on one type of test. All 10 who got the booster shot developed neutralizing antibodies on at least one test.
The neutralizing antibody levels observed were comparable to those from the plasma of people who had recovered from coronavirus infections, a rough guide that scientists believe could indicate whether a vaccine might ultimately protect against infection.
Notably, Oxford researchers also found signs of T cell responses, which peaked at the two week mark and were maintained through two-months post vaccination in 53 participants who were evaluated.
The vaccine seemed generally safe. Common side effects observed in testing were chills, fatigue, fever, and headache, though researchers said those cases were tolerable and treatable with aspirin. There were no serious side effects that were deemed related to treatment. A small portion of each group — 56 who got the coronavirus vaccine and 57 in the control arm — received prophylactic aspirin to help tamp down the fever-like symptoms.
The results are, by far, the largest set of data to be published on an experimental coronavirus vaccine. Recent data on rival vaccines from Moderna and BioNTech and partner Pfizer were each from 45 adults. Some 108 volunteers got a vaccine from China-based firm Cansino Biologics in a Phase 1 study. (Data from the CanSino study were published separately in The Lancet on Monday.)
All of those vaccines showed they can help the body produce antibodies that can neutralize the coronavirus at levels similar to those in patients who have recovered from an infection. But the antibodies produced by the Moderna and Pfizer/BioNTech vaccines only materialized after multiple weeks and a booster shot, and a portion of people may prove immune to CanSino’s candidate.
Oxford researchers aimed for a single, high-dose regimen, hoping to quickly spur production of neutralizing antibodies. The results from the two-dose regimen suggest a booster shot might help raise antibody levels, but didn’t seem to affect the T cell response.
Adrian Hill, the director of Oxford’s Jenner Institute, said one and two-dose regimens are being evaluated in further testing. If a second shot is necessary, it would be more difficult for AstraZeneca to manufacture the billions of doses globally that it’s targeted.
Like the shots from Moderna and Pfizer/BioNTech, Oxford and AstraZeneca’s vaccine carries genetic material meant to teach the body to recognize and target the “spike” protein that the coronavirus uses to enter cells. Each does it differently, however. While Moderna and the Pfizer/BioNTech team use messenger RNA to encode for the spike protein, Oxford and AstraZeneca use DNA.
Getting those instructions into the body’s cells is the next challenge. Both Moderna and Pfizer/BioNTech use lipid nanoparticles — tiny fat bubbles — to deliver the blueprints for the spike protein into cells. Oxford and AstraZeneca, meanwhile, uses a genetically modified virus — a form of the adenovirus that causes common colds in chimpanzees — for the task.
