Two phase 1 clinical trials of a nasal spray containing influenza virus–specific monoclonal antibodies conclude that it’s safe—although it won’t replace flu vaccination because it stays in the nose for only a few hours, researchers say.
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.
Harvard researchers led the evaluation of the CR9114 nasal spray, which was developed at Leyden Laboratories in The Netherlands under a license from Johnson & Johnson.
“Direct intranasal delivery of monoclonal antibodies may enable protection at the portal of entry of respiratory viruses,” the authors wrote.
Antibody binding suggests neutralizing potential
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 (time for half a given quantity to be eliminated) was roughly three hours, necessitating twice-daily administration.
Direct intranasal delivery of monoclonal antibodies may enable protection at the portal of entry of respiratory viruses.
Post-administration nasal samples bound hemagglutinin (substance on the influenza virus surface that facilitates cell entry) 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 the authors said suggests their neutralizing potential.
In expert reactions, Isabelle Montgomerie, PhD, of the Malaghan Institute of Medical Research, said that intranasal delivery produces high antibody concentrations using much smaller doses than intravenous antibody treatments.
"This study closely aligns with research currently under way in New Zealand at the Malaghan Institute of Medical Research, where we are developing influenza antibody therapies using mRNA technology and working with chemists at the Ferrier Research Institute to facilitate delivery directly to the nasal passage, with the aim of producing more affordable and longer-lasting protection,” she said.