A Randomized, Controlled Trial of an Aerosolized Vaccine against Measles

Abstract

BACKGROUNDAerosolized vaccine can be used as a needle-free method of immunization against measles, a disease that remains a major cause of illness and death. Data on the immunogenicity of aerosolized vaccine against measles in children are inconsistent. METHODSWe conducted an open-label noninferiority trial involving children 9.0 to 11.9 months of age in India who were eligible to receive a first dose of measles vaccine. Children were randomly assigned to receive a single dose of vaccine by means of either aerosol inhalation or a subcutaneous injection. The primary end points were seropositivity for antibodies against measles and adverse events 91 days after vaccination. The noninferiority margin was 5 percentage points. RESULTSA total of 1001 children were assigned to receive aerosolized vaccine, and 1003 children were assigned to receive subcutaneous vaccine; 1956 of all the children (97.6%) were followed to day 91, but outcome data were missing for 331 children because of thawed specimens. In the per-protocol population, data on 1560 of 2004 children (77.8%) could be evaluated. At day 91, a total of 662 of 775 children (85.4%; 95% confidence interval [CI], 82.5 to 88.0) in the aerosol group, as compared with 743 of 785 children (94.6%; 95% CI, 92.7 to 96.1) in the subcutaneous group, were seropositive, a difference of −9.2 percentage points (95% CI, −12.2 to −6.3). Findings were similar in the full-analysis set (673 of 788 children in the aerosol group [85.4%] and 754 of 796 children in the subcutaneous group [94.7%] were seropositive at day 91, a difference of −9.3 percentage points [95% CI, −12.3 to −6.4]) and after multiple imputation of missing results. No serious adverse events were attributable to measles vaccination. Adverse-event profiles were similar in the two groups. CONCLUSIONSAerosolized vaccine against measles was immunogenic, but, at the prespecified margin, the aerosolized vaccine was inferior to the subcutaneous vaccine with respect to the rate of seropositivity.

Variability in Humoral Immunity to Measles Vaccine: New Developments

“…Therefore, there has been considerable interest in evaluating different routes of administration. A recent clinical trial found that seroconversion rates were 10% lower for the aerosolized measles vaccine than for the conventional injected vaccine [83, 84]. However, the measles vaccine administered via microneedle patch has shown promise in non-human primate studies [85].…”

Assessing the Potential Cost-Effectiveness of Microneedle Patches in Childhood Measles Vaccination Programs: The Case for Further Research and Development

“…In addition to the cost advantages, microneedle patches potentially have several important logistical advantages (e.g., reduced cold chain requirements, fewer trained staff required) that could increase vaccine coverage, especially in hard-to-reach communities. Other vaccine-related technologies, such as aerosolized vaccines, could also offer advantages over the subcutaneous vaccination [19]. These technologies should also be carefully monitored and evaluated.…”

Harnessing Local Immunity for an Effective Universal Swine Influenza Vaccine

“…Whether LAIVs will have much enhanced protective efficacy if deliberately delivered to the LRT requires thorough investigation to determine whether this is more efficient in inducing both homologous and heterologous protection against SI in pigs. However, despite major advances in aerosol vaccine delivery in humans [53] and some examples of local delivery to livestock, no practical devices for aerosol delivery are yet available for farm animals in the field.…”