Aerosolized Measles Vaccine Fails Noninferiority Trial in India

Robert S. Baltimore, MD reviewing Low N et al. N Engl J Med 2015 Apr 16.

Although aerosolized measles vaccine was immunogenic, its seropositivity rate was 9.2 percentage points lower than that of subcutaneous vaccine, exceeding the prespecified 5 percentage point noninferiority margin.

Measles vaccine is usually given by subcutaneous injection. An aerosolized measles vaccine (AMV) could be administered by individuals with less training and would not require sterile needles and syringes. The technology has been developed, but previous trials comparing AMV with conventional subcutaneous measles vaccine (SMV) have shown inconsistent efficacy results. A new study, performed at eight primary care clinics in India, was designed to determine whether AMV would be noninferior to SMV — defined as ≤5 percentage points lower — in inducing a protective immune response in infants.

In this open-label trial, 2004 infants aged 9.0 to 11.9 months were randomized to receive WHO-licensed measles vaccine, produced by the Serum Institute of India, by either aerosol inhalation or subcutaneous injection. AMV was given in a 0.2-mL dose nebulized for 30 seconds through a single-use, nonvented face mask. Blood samples obtained 91 days after immunization were tested for serum antibodies against measles by an enzyme-linked immunosorbent assay, a plaque-reduction neutralization test, or both.

In all, 775 (77.4%) of the AMV-group vaccinees and 785 (78.2%) of the SMV-group vaccinees completed follow-up and had specimens that could be analyzed. Seropositivity rates at day 91 were 85.4% for AMV and 94.6% for SMV — a difference of −9.2 percentage points. Thus AMV did not show noninferiority in per-protocol analysis by the prespecified 5 percentage point margin.

CITATION(S):

Low N et al. A randomized, controlled trial of an aerosolized vaccine against measles. N Engl J Med 2015 Apr 16; 372:1519.