The current COVID-19 vaccines have protected millions of Americans from serious illness and death, but they still have a major limitation: They’re not particularly good at blocking infections.
Recent research led by Boston scientists suggests a possible solution. Delivering vaccines directly to the lungs by using a device similar to an asthma inhaler can build up a far larger army of immune cells where it counts: in the breathing passages, where viruses first enter the body. That army can intercept and kill COVID-19 virus particles before they make us sick.
In the study, detailed in a recent issue of Nature, the team compared immune responses to vaccines delivered to the lungs with immune responses to vaccines delivered as shots.
“When we gave the vaccine directly to the lung, we saw a dramatic improvement in ... immunity and protection in the lung itself and in the nose, leading to near complete protection against infection,” said Dr. Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center and the senior author on the paper. Current vaccines raise antibodies in the blood, he said, but have a minimal effect in raising antibody and T-cell responses in the nose and the lungs — “where it really matters if you want to block infection.”
The results, Barouch argues, provide a powerful “proof of concept” for the idea that future boosters should be delivered using a device similar to an asthma inhaler.
The paper is just the latest to suggest that it might be possible to block infections and build up a protective force field of immune cells in the nose and lungs by changing how we deliver vaccines. Last month, Chinese researchers published the results of a study in which researchers administered an inhaled vaccine to 11,000 people, demonstrating that the approach was both safe and more effective than shots delivered to the muscles, Barouch said. The vaccine is being rolled out on a large scale in China.
Nasal vaccines also show promise. In a paper recently posted to the open-access preprint site BioRxiv, a team of researchers led by Dr. Robert Seder, chief of the cellular immunology section at the National Institute of Allergy and Infectious Diseases, showed they could boost the ability of monkeys to fight off infection by delivering a booster directly to the nose or lungs using an FDA-approved nose sprayer or an FDA-approved nebulizer.
After delivering the booster, Seder’s team waited five months before exposing the monkeys to the XBB strain, among the most highly transmissible variants. The immune response, he said, “shut the virus down,” far outperforming the animals that were boosted using shots. The study, he said, is under review at a peer-reviewed journal.
Dr. Peter Hotez, a vaccine expert and dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston who was not involved in either study, said he welcomes more research into inhalers and nasal sprays, in part because they could increase booster uptake among those who are scared of needles.
But he disputed the idea that current boosters can’t block infection. He pointed to early studies of the initial vaccines that found a significant number of virus-fighting immune cells present in the nose and throat. This small army of antibodies, he said, was able to prevent infection. But as the virus mutated, the ability of those antibodies to elicit an effective immune attack waned.
“There’s got to be a good match between the virus and the vaccine, and if it’s not there, it doesn’t matter what delivery system you’re going to use, you’re not going to stop asymptomatic infection,” he said.
Seder disagrees with Hotez’s suggestion that there is little advantage to applying the booster directly to the airways. When a booster is delivered as a shot, some antibodies will eventually reach the lungs and nose. But the amount of antibodies present in the airwaves will be far higher if the booster is delivered directly to those areas of the body — and since the proportion of those antibodies able to recognize the virus often wanes as the virus mutates, those extra antibodies are needed.
Seder’s and Barouch’s studies used either the Johnson & Johnson vaccine or similar ones based on an adenovirus. Using the approach with the existing mRNA vaccines would require new formulations stable enough to survive in the new environment, Barouch said. Seder said his group is working on the problem, as are a number of others.
Sprayed or inhaled vaccines are also among the areas of focus of Project NextGen, a $5 billion federal effort that aims to accelerate and streamline the development of next-generation vaccines and treatments.
But a timeline for human trials remains unclear. Seder notes that mucosal vaccines will need to be tested extensively for safety. He added that the Indian company Bharat Biotech has administered a vaccine similar to the one used in the NIH study to large numbers of people in South Asia, though it did so by placing drops directly into the nose, rather than using the FDA-approved sprayer used in his study. Ocugen, Inc., a Pennsylvania-based biotechnology company, has licensed the technology used in the NIH trial, and a spokesperson said the company hopes to begin human safety trials next year.
Adam Piore can be reached at firstname.lastname@example.org.