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A person in a white shirt activates a nasal spray
A person in a white shirt activates a nasal spray

Oxford-AstraZeneca Nasal COVID-19 Vaccine Falters in Clinical Trial

Researchers say they’re abandoning the project in its current form—one of several that aims to induce what’s known as mucosal immunity against SARS-CoV-2.

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Dan Robitzski

Dan is a Staff Writer and Editor at The Scientist. He writes and edits for the news desk and oversees the “The Literature” and “Modus Operandi” sections of the monthly TS Digest and quarterly print magazine. He has a background in neuroscience and earned his master's in science journalism at New York University.

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Since early in the pandemic, researchers have been working to develop a vaccine for SARS-CoV-2 that could be administered in the form of a nasal spray, as such a spray would be simpler to administer than an injection and would hypothetically enhance immune protections where the coronavirus enters the body. Unfortunately, one such experimental vaccine, developed by scientists at the University of Oxford and AstraZeneca, performed dismally in a small Phase 1 clinical trial, according to results published Tuesday (October 10) in eBioMedicine, and the researchers behind the project say they plan to abandon it, at least in its current form.

The nasal approach is intended to enhance mucosal immunity, or the immune system’s ability to fend off pathogens at the point of contact on mucosal membranes rather than with antibodies or immune cells circulating in the bloodstream. The aim is to prevent more cases of COVID-19 than could be done with injected vaccines, which excel at preventing serious disease and death but not at heading off mild infections. However, the new study’s results show that fewer than half of the study participants produced detectable levels of mucosal antibodies a month following administration, and in those who did, the level of SARS-CoV-2 antibodies was lower than that conferred by either injected vaccines or prior SARS-CoV-2 infection. University of Oxford researchers say that the results don’t warrant further testing, according to The Guardian, which notes that one problem with the approach may be that much of the vaccine is accidentally swallowed and digested in the stomach before it can do much good.

See “Nasal Vaccines Are Commercially High Risk, Perhaps High Reward

“The nasal spray did not perform as well in this study as we had hoped,” Sandy Douglas, the chief investigator on the trial at Oxford’s Jenner Institute, says in a university press release. “Delivery of vaccines to the nose and lungs remains a promising approach, but this study suggests there are likely to be challenges in making nasal sprays a reliable option.”

In the trial, 30 unvaccinated volunteers received a low, medium, or high dose of the nasal vaccine—14 were given a second, identical dose 28 days later, and 12 others were given an injected vaccine dose 3 to 7 weeks later. The rest of the participants only received their initial nasal dose. Additionally, 12 other volunteers who had already received vaccine injections were given the nasal spray as a booster. While no safety issues were detected, seven of the participants developed symptomatic SARS-CoV-2 infection within the four-month follow-up period following vaccination.

Other nasal vaccines have shown more promise: The Chinese government recently approved CanSino Biologics’ nasal vaccine, which is delivered as a mist generated by a nebulizer. And last month, India’s government approved Bharat Biotech’s vaccine, which is dropped into the nose, according to Reuters.

See “What We Know About Getting a Second Booster Shot of COVID-19 Vaccines

University of Cambridge vaccinologist Gordon Dougan, who didn’t work on the University of Oxford and AstraZeneca nasal vaccine, tells The Guardian that the concept of nasal vaccines for COVID-19 is still promising, adding that data from the trial as well as that from the Chinese and Indian vaccines can help experts figure out the best way to proceed.

“We need better science to understand how to induce immunity through nasal and oral delivery,” he says. “It’s still not well understood. Nasal vaccines offer an opportunity to induce local immunity, potentially limiting transmission, which will be vital to prevent the emergence of vaccine escape variants.”

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