Safety and immunogenicity of an upper-range release titer measles-mumps-rubella vaccine in children vaccinated at 12 to 15 months of age: a phase III, randomized study.

The titer of live attenuated viral vaccines, such as MMR vaccines, varies between batches and over the shelf-life of a batch, with the highest titer expected at batch release. As higher titers may theoretically lead to increased reactogenicity, we compared the safety profile of an upper-range release titer MMR-RIT lot with commercial MMR II lots in a phase III, randomized, controlled study (NCT02184572). We vaccinated 1736 children with MMR-RIT (N = 1164) or MMR II (N = 572), both administered as first doses with varicella, hepatitis A, and pneumococcal conjugate vaccines at 12-15 months of age. The incidence of fever 5-12 days post-vaccination was comparable following MMR-RIT and MMR II vaccination: 4.2% vs 3.1% (difference: 1.1%) for fever > 39.0 degrees C and 18.2% vs 17.1% (difference: 1.1%) for fever >= 38.0 degrees C, which met the primary objective. Two cases of febrile convulsions (one considered vaccination-related) were reported within 43 days post-MMR-RIT. During Days 0-42, rashes were reported for 24.4% (MMR-RIT) and 27.4% (MMR II) of children; measles/rubella-like rashes for 5.8% and 4.7%, respectively. Measles-like illnesses were reported for 1.5% (MMR-RIT) and 0.9% (MMR II) of children 5-12 days post-vaccination. One serious adverse event, immune thrombocytopenic purpura following MMR II vaccination, was considered vaccination-related. Immune responses were similar in both groups. In summary, the safety profile of an upper-range release titer MMR-RIT lot was in line with that of commercial MMR II lots, with similar rates of fever and other MMR-specific symptoms and low rates of measles-like illnesses reported with both vaccines.