Response to different measles vaccine strains given by aerosol and subcutaneous routes to schoolchildren: A randomised trial

Background: More than one dose of measles vaccine is necessary for the sustained control of measles. The aerosol route is thought to be more immunogenic for booster doses than traditional subcutaneous injections, so we did a randomised comparative trial of aerosol and subcutaneous measles vaccines in South African schoolchildren. Methods: 4327 schoolchildren (aged 5-14 years), assigned by block randomisation of classrooms, received standard titre doses of either Schwarz or Edmonston-Zagreb measles vaccines subcutaneously or by aerosol. Blood samples for antibody assay were collected before vaccination, at 1 month, and 1 year after vaccination. The main endpoints (antibody titres at 1 month and 1 year) were compared between groups. Findings: 992 children had antibody titre data available for all timepoints. 14 (3.6%) of 385 children who received Edmonston-Zagreb vaccine by aerosol were seronegative 1 year after vaccination, compared with 28 (8.6%) of 326 children who received Edmonstan-Zagreb subcutaneous vaccine and 39 (13.9%) of 281 children who received Schwarz subcutaneous vaccine. At 1 month, 326 (84.7%) children who received aerosol Edmonston-Zagreb vaccine had seroconverted, compared with 257 (78.8%) who received subcutaneous Edmonston-Zagreb vaccine and 176 (62.6%) who received subcutaneous Schwarz vaccine. At 1 month, only 116 (22.7%) of 511 children in the Schwarz aerosol group had seroconverted; this aerosol vaccine had no detectable potency after 2 min of nebulisation. There were no serious side-effects: about 5% of children in each group had a rash within 2 weeks of vaccination. Interpretation: An aerosol vaccination method that uses currently available devices and a suitably stable vaccine is effective and acceptable. This form of delivery is adaptable to mass campaigns, avoids the risks associated with injections, and could help measles eradication.