An aerosolized measles vaccine proved to be immunogenic but inferior to the subcutaneous vaccine in inducing seropositivity among infants in rural India, according to a report published online April 16 in the New England Journal of Medicine.
Aerosolized delivery of a measles vaccine could prove especially helpful in resource-poor countries where major measles outbreaks continue to occur because of poor health service infrastructure, but data concerning the efficacy of this form of delivery have been inconsistent. “Given the established record of injectable measles vaccine, alternative delivery methods should show noninferiority,” wrote Dr. Nicola Low of the Institute of Social and Preventive Medicine, University of Bern (Switzerland), and her associates.
They performed a randomized, open-label noninferiority trial comparing a primary dose of aerosolized measles vaccine (1,001 children) against subcutaneous measles vaccine (1,003 children) among babies aged 9-11.9 months living in villages in rural India. The primary endpoint – seropositivity for serum antibodies against measles at 91 days after vaccination – was 85.4% for aerosolized vaccine and 94.6% for subcutaneous vaccine. This difference of 9.2 percentage points did not reach the threshold for noninferiority, which was 5.0 percentage points, the investigators said (N. Engl. J. Med. 2015;372:1519-29 [doi:10.1056/NEJMoa1407417]).
Among the children who did achieve seropositivity, however, the geometric mean concentrations of measles antibodies were similar between the two study groups.
Adverse-event profiles were similar between aerosolized and subcutaneous vaccine, and adverse events were rare. The most common effects judged likely to be related to the vaccines were rash, coryza, cough, diarrhea, and fever.
After this study was designed, experts recommended providing a second dose of measles vaccine to protect children who did not respond to the first dose. Using this two-dose strategy, the aerosolized formulation induced higher and more sustained levels of seropositivity than the subcutaneous formulation in studies of school-aged children in South Africa. So it is possible that the aerosolized measles vaccine may prove to be noninferior in future studies involving a different dosing schedule and an older pediatric patient population, Dr. Low and her associates noted.
This study was funded by the Bill and Melinda Gates Foundation. The Serum Institute of India provided vaccines free of charge and Aerogen provided the delivery devices free of charge. Dr. Low reported several grants plus monies paid to her institution from the World Health Organization for projects about vaccines and sexually transmitted infections; her associates reported ties to the Serum Institute of India, Aerogen, and Dance Biopharm. One associate has a patent pending on an aerosol device licensed to Novartis and another has a patent pending related to vaccine nebulizers.