Nasal Spray Vaccines Show Promise Against Respiratory Infections in Early Studies
Researchers at Stanford and Harvard are developing nasal spray vaccines offering broad protection against respiratory infections, with early animal and phase 1 human trials showing safety and potential efficacy.
A Stanford University team has tested a nasal spray vaccine in animals that could protect against all coughs, colds and flus, as well as bacterial lung infections, and may even ease allergies. The researchers still need to conduct human clinical trials of their "universal vaccine."
The approach described in the journal Science does not train the immune system. Instead it mimics the way immune cells communicate with each other. It is given as a nasal spray and leaves white blood cells in the lungs – called macrophages – on "amber alert" and ready to jump into action no matter what infection tries to get in.
The effect lasted for around three months in animal experiments. The researchers showed this heightened state of readiness led to a 100-to-1,000-fold reduction in viruses getting through the lungs and into the body. For those that did sneak through, the rest of the immune system was "poised, ready to fend off these in warp speed time."
The team showed the vaccine also protects against two species of bacteria - Staphylococcus aureus and Acinetobacter baumannii. The way it steers the immune system towards fighting an infection also seemed to reduce the response to house dust mite allergens – which are a trigger of allergic asthma.
The approach marks a "radical departure" from the way vaccines have been designed for more than 200 years. Current vaccines train the body to fight one single infection. A measles vaccine protects against only measles and a chickenpox vaccine protects against only chickenpox. This is how immunisation has worked since Edward Jenner pioneered vaccines in the late 18th Century.
The vaccine was given as a nasal spray in the experiments, but may need to be breathed in through a nebuliser to reach the depths of human lungs. It is not known whether the same effect can be achieved in people or how long the immune system would stay in amber alert. There are differences in the immune systems between mice and humans, including immunity being shaped by decades of infections.
The researchers are planning trials where one person is vaccinated and then deliberately infected to see how their body copes. There may also be consequences to dialling up the immune system beyond its normal state – raising questions of immune disorders.
The research team does not think the immune system should be permanently dialled up and think such a vaccine should be used to complement rather than replace current vaccines. In the first stages of a pandemic, like early 2020 with Covid, a universal vaccine could buy time and save lives while a specialist vaccine was being developed. The other scenario is at the start of winter when the usual wide range of winter bugs start to spread.
Separately, Harvard researchers completed two phase 1 clinical trials of a nasal spray containing influenza virus–specific monoclonal antibodies, concluding that it's safe—although it won't replace flu vaccination because it stays in the nose for only a few hours. The trial findings, published in Science Translational Medicine, form the basis for efficacy studies in people and suggest that the spray may fill a gap by quickly providing short-term protection in a flu pandemic, particularly for high-risk populations such as health care workers.
The team evaluated the CR9114 nasal spray, which was developed at Leyden Laboratories in The Netherlands under a license from Johnson & Johnson. The team first assessed the spray's efficacy in mice and macaques, demonstrating safety at all tested doses and schedules. In macaques, CR9114's half-life was roughly three hours, necessitating twice-daily administration.
Post-administration nasal samples bound hemagglutinin from strains of influenza A and B and neutralized A(H1N1), A(H5N1), and A(H3N2) better than baseline samples. Twice-daily dosing protected macaques against an influenza virus challenge.
Phase 1 trials involving a total of 143 healthy people showed the accumulation of antibodies in the nose that could bind to influenza A and B in culture, which suggests their neutralizing potential. Intranasal delivery produces high antibody concentrations using much smaller doses than intravenous antibody treatments.