COVID-19: Could nasal vaccines be the better solution?

By Rahul Vaimal, Associate Editor
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COVID-19 vaccines that are nearest to the finish line are designed to be injected into the arm. Researchers are looking at whether they can get better protection from vaccines that combat the virus at the point of attack itself which is the nose and mouth.

In human testing, most injected vaccines require two shots for effectiveness and developers are still not even sure if they will prevent infections. With inhaled vaccines that specifically target the airway cells the virus invades, scientists are hoping to produce superior immune responses.

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In the US, Britain and Hong Kong, there are alternatives to traditional injection shots including sprayed and inhaled vaccines under development. This could play an important role in helping society avoid restrictions that have upset economies and daily life. Among their aims is to stop the growth of the pathogen in the nose, a point from which it can spread to the rest of the body and to other individuals.

“Local immunity matters,” said Frances Lund, an immunologist working with biotech company Altimmune Inc. on an early-stage nasal inoculation. “The vaccines that can be delivered to generate local immunity will have some advantages over vaccines that are delivered systemically.”

Benefits of nasal vaccines

Many early developers of vaccines relied on the familiar injection path, seen as the easiest way to protect the world from disease. Some of the distinctive characteristics of the lungs, nose and mouth, which are lined with mucosa, are counted on by inhaled vaccine makers. There are high levels of immune proteins, called IgA, which provide better protection against respiratory viruses.

They theorize that activating these immune weapons can protect areas deeper in the lungs where the SARS-CoV-2 does the most damage. They can also increase the chances of vaccines to block transmission of the virus.

“The first generation of vaccines are probably going to protect a lot of people,” said Michael Diamond, an infectious disease specialist at a US university. “But I think it’s the second- and third-generation vaccines and maybe intranasal vaccines will be a key component of this, that ultimately are going to be necessary. Otherwise, we’ll continue to have community transmission.”

Diamond and his team found in a study of mice in August that the delivery of an experimental vaccine through the nose produced a powerful immune response across the body; the strategy was particularly successful in the nose and respiratory tract, preventing infection from taking hold. The rights for this single-dose technology was obtained by India’s Bharat Biotech and US-based Precision Virologics last month.

There are other functional benefits for vaccines that are sprayed into the nose or inhaled like the fact that they may not need needles, do not have to be stored and shipped at low temperatures and may decrease the need for them to be administered by healthcare professionals.

“When you’re thinking about trying to deliver that across the world, if you don’t need to have an injectable vaccine, your compliance goes up because people don’t like getting shots,” according to Lund, the Alabama-based researcher. “But secondly, the level of expertise needed to administer that vaccine is significantly different.”

After promising trials in mice, Altimmune, based in the UK, plans to begin human testing with a nasal vaccine in the fourth quarter. Scientists at Oxford University, where AstraZeneca Plc has a promising shot under production, and Imperial College London are also planning studies of slightly different inhaled vaccines.

Similar to other asthma treatments, the experimental immunizations in Britain will be administered via a mouthpiece in an aerosol. Imperial researchers point to evidence that the delivery of influenza vaccines via a nasal spray can shield individuals from disease and help minimize transmission; they are keen to investigate whether the case is the same with SARS-CoV-2.

According to experts, data from studies of the inhaled Oxford vaccine could be available early next year, followed by results from Imperial College in the second quarter.

In recent months, Imperial College has been advancing studies of a COVID-19 vaccine using RNA technology that can be administered by traditional shots and plans to extend its trials by year-end to 20,000 individuals. Oxford, one of the front-runners in the global quest for immunization, is in the final stage and both techniques could be conducive to inhalation.

“This is a virus that’s transmitted through your respiratory tract, so if you want a vaccine that will really prevent infection and onward transmission you want to have an antibody response in your nose, in your lungs,” says Robin Shattock, an infectious disease specialist said. “The most efficient way to induce that is by inoculating through that route.”

Hong Kong (in China) researchers are looking for an intranasal vaccine that would provide safety against influenza and COVID-19 simultaneously. The first phase of human tests will start next month, said Yuen Kwok-Yung, chair of infectious diseases at the Department of Microbiology of the University of Hong Kong.

When the world looks to expand on the first wave of products, he said, the ambition is to come up with the “vaccine of choice.”

Questions are yet to be answered regarding the durability of nasal vaccinations, and they are at an early stage. Despite the benefits, according to Nick Jackson, head of programs and technology at the Coalition for Epidemic Preparedness Innovations (CEPI), delivery devices are also more complex.

Nevertheless, researchers said that targeting the airways might pay off down the road. CEPI has also provided support for the Hong Kong project and is open to more investment in unconventional approaches to vaccines as part of an attempt to bring billions of doses to every corner of the globe, Jackson said.

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