A randomized, controlled trial of an aerosolized vaccine against measles.

Kingsley Onokalah, PharmD candidate 2015, Mercer University College of Pharmacy

Measles is a highly contagious disease that may result in outbreaks in populations where 10% of the people are susceptible. Typical signs and symptoms include fever and rash.For prevention, the Centers for Disease Control and Prevention (CDC) recommend two doses of measles-containing vaccine be administered at least four weeks apart in children on or after the first birthday.2

Per the CDC, multiple measles vaccine products are available in the United States for intramuscular, intravenous, and subcutaneous administration.2  Aerosolized measles vaccine delivered via nebulization has been used in over four million children since 1980.  However, Low et al note that data obtained from reviews of 16 studies assessing the efficacy of aerosolized vaccine against measles in children are inconsistent.3

Title: A randomized, controlled trial of an aerosolized vaccine against measles.
Design Randomized, open-label noninferiority trial; N= 2004
Objective To compare the immunogenicity of measles vaccine delivered via a

nebulizer/vaccine combination product with a licensed subcutaneous vaccine in infants who are eligible to receive a first dose of measles vaccination but are no older than 12 months

Study Groups Measles aerosolized vaccine (n= 1001) and subcutaneous measles vaccine (n= 1003)
Methods Children in India age nine to 11.9 months were randomized in a 1:1 ratio to receive a single dose of measles vaccine by either subcutaneous injection or aerosol inhalation.  Seropositivity is defined as 0.1 or more optical-density units on an enzyme-linked immunosorbent assay (ELISA) or, in samples containing less than 0.1 optical-density units, a measles antibody concentration of 120 mIU per milliliter or more as measured with the use of a plaque-reduction neutralization test (PRNT).  All samples at baseline and day 91 were tested by means of ELISA.  A pre-specified non-inferiority margin of five percentage points was used to determine effectiveness of the aerosolized vaccine.
Duration December 20, 2009 to April 5, 2010
Primary Outcome Measure Measles seropositivity at day 91 after vaccination
Baseline Characteristics Aerosolized vaccine group: Under age ten months (72.9%), female sex (48.8%), clinically significant illness in past three months (2.9%), measles antibodies not present at baseline (76.1%)

Subcutaneous vaccine group: Under age ten months (74.7%), female sex (48.8%), clinically significant illness in past three months (2.4%), measles antibodies not present at baseline (76.6%)

Results Day 91 measles seropositivity in per-protocol population:

Aerosolized vaccine group: 662 of 775 children (85.4%; 95% confidence interval (CI) 82.5 to 88.0)

Subcutaneous vaccine group: 743 of 785 children (94.6%; 95% CI 92.7 to 96.1)

Adverse Events Common Adverse Events:

Aerosolized vaccine group: coryza (44 %), cough (26.3%), diarrhea (28.1%), fever (28.6%), vomiting (9.6%)

Subcutaneous vaccine group: coryza (38.7%), cough (27%), diarrhea (28.7%), fever (27.5), vomiting (9.1%)

Serious Adverse Events: None related to study vaccines
Percentage that Discontinued due to Adverse Events: None
Study Author Conclusions Aerosolized vaccine against measles, as compared with subcutaneously administered vaccine, resulted in statistically inferior levels of seropositivity at 91 days in children who were 9.0 to 11.9 months of age.  Profiles of adverse events were similar in the two groups, and adverse events associated with vaccination were rare.

Results showed that aerosolized measles vaccine results in lower seropositivity in children when compared to the subcutaneous injection.  A limitation of this study for applicability to the United States was the inclusion of children under the age of 12 months, as the CDC recommends the measles vaccine be administered on or after a child’s first birthday.  Future trials could investigate the effectiveness of aerosolized measles vaccine in comparison to others routes of administration (intravenously or intramuscularly).

References:

  1. Moss WJ, Griffin DE. Measles. Lancet. 2012 Jan 14;379(9811):153-64.
  2. McLean HQ, Fiebelkorn AM, Temte JL, et al. Prevention of Measles, Rubella, Congenital Rubella Syndrome, and Mumps, 2013: Summary Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2013 Jun 14;62(RR-04):1-34.
  3. Low N, Bavdekar A, Jeyaseelan L, et al. A randomized, controlled trial of an aerosolized vaccine against measles. N Engl J Med. 2015;372:1519-29. DOI: 10.1056/NEJMoa1407417.
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