Most vaccines in human trials require two injections to be effective, and developers are not yet sure whether they will prevent infections. Scientists hope to elicit superior immune responses with inhaled vaccines that directly target cells in the airways that the virus invades.
An alternative to conventional jabs, aerosol and inhaled vaccines that is being developed in the US, Britain and Hong Kong could play an important role in helping society escape the restrictions that have disrupted economies and everyday life. Among its objectives is to prevent the pathogen from growing in the nose, a point from which it can spread to the rest of the body and to other people.
“Local immunity is important,” said Frances Lund, an immunologist at the University of Alabama at Birmingham who works with Biotech Altimmune Inc on an early stage nasal inoculation. “Vaccines that can be delivered to generate that will have some advantages over vaccines that are administered systemically.”
Most of the early vaccine developers focused on a familiar route, injections, considered the fastest way to protect the world from disease. Manufacturers of inhaled vaccines have some of the unique characteristics of the lungs, nose, and throat, which are lined with mucosa. This tissue contains high levels of immune proteins, called IgA, which provide better protection against respiratory viruses.
Activating these immune weapons, they theorize, can protect deeper areas of the lungs where SARS-CoV-2 causes the most damage. They can also improve the chances that vaccines will block transmission.
“The first generation of vaccines will probably protect a lot of people,” said Michael Diamond, an infectious disease specialist at the University of Washington in St Louis. “But I think it’s the second and third generation vaccines, and perhaps intranasal vaccines will be a key component of this, the ones that will ultimately be necessary. Otherwise, we will continue to have community transmission. ”
In a mouse study in August, Diamond and his team found that administering an experimental vaccine through the nose created a strong immune response throughout the body; the approach was especially effective in the nose and respiratory tract, preventing the infection from taking hold. India’s Bharat Biotech and St. Louis-based Precision Virologics won the rights to the single-dose technology last month.
Vaccines that are sprayed through the nose or inhaled can have other practical benefits. They do not require needles, may not need to be stored and shipped at low temperatures, and can reduce the need for healthcare workers to administer them.
“When you’re thinking about trying to distribute that around the world, if you don’t need an injectable vaccine, your compliance increases because people don’t like getting shots,” according to Lund, the Alabama-based researcher. “But second, the level of expertise required to administer that vaccine is significantly different.”
Altimmune, based in Gaithersburg, Maryland, plans to enter human trials with a nasal vaccine in the fourth trimester after positive studies in mice. Scientists at the University of Oxford, where a promising vaccine was designed in development at AstraZeneca Plc, and Imperial College London are also planning studies of slightly different inhaled vaccines.
Experimental immunizations in Britain would be administered through an aerosol mouthpiece, similar to some asthma therapies. Imperial researchers point to evidence that administering flu vaccines through a nasal spray can protect people against illness and help reduce transmission; they are eager to explore whether that is also the case for SARS-CoV-2. AstraZeneca manufactures the FluMist nasal spray vaccine.
Data from the inhaled Oxford vaccine studies could arrive early in the new year, followed by Imperial’s results in the second quarter, according to Robin Shattock, an infectious disease specialist at Imperial College.
“We don’t know if it will work well, but if it works, then it could be very important,” he said in an interview.
In recent months, Imperial College has advanced studies of a Covid vaccine using RNA technology that would be delivered via conventional injections and plans to expand its trials to 20,000 people by the end of the year. Oxford, one of the pioneers in the global quest for an inoculation, is in the final stages of testing a vaccine that uses a harmless virus to transport the pathogen’s genetic material into cells and generate an immune response. Both techniques can lead to inhalation, Shattock said.
“This is a virus that is transmitted through the respiratory tract, so if you want a vaccine that really prevents infection and further transmission, you have to have an antibody response in the nose, in the lungs,” Shattock said. “The most efficient way to induce that is by inoculating through that route.”
Researchers in Hong Kong are targeting an intranasal vaccine that simultaneously offers protection against influenza and Covid-19. The first phase of human testing will begin next month, said Yuen Kwok-Yung, chair of infectious diseases at the department of microbiology at the University of Hong Kong.
The ambition is to come up with the “vaccine of choice,” as the world seeks to build on the first wave of products, he said.
Questions about the durability of nasal vaccines have yet to be resolved and are in an early stage. Despite the benefits, the delivery devices are also more complex, according to Nick Jackson, head of programs and technology for the Coalition for Epidemic Preparedness Innovations.
“A needle and syringe work very well,” he said.
Still, the researchers said targeting the airways could pay off in the future. Oslo-based CEPI has provided funding for the Hong Kong project and is open to new investments in vaccines that take unconventional approaches as part of an effort to deliver billions of doses to every corner of the world, Jackson said. .
“Whether it’s our vaccine or another one that goes through an intransasal route that actually succeeds in interrupting transmission and the pandemic, my hat is off,” Diamond said. “If we contribute by forcing or pushing these companies to think of an alternative route to what could be a successful platform, then we have done our job.”
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