M-M-R II Mechanism of Action

Pharmacology: Mechanism of Action: M-M-R II vaccination induces antibodies to measles, mumps, and rubella associated with protection which can be measured by neutralization assays, hemagglutination-inhibition (HI) assays, or enzyme linked immunosorbent assay (ELISA) tests. Results from efficacy studies or effectiveness studies that were previously conducted for the component vaccines of M-M-R II were used to define levels of serum antibodies that correlated with protection against measles, mumps, and rubella [see Clinical Studies as follows].
Persistence of Antibody Responses After Vaccination: Neutralizing and ELISA antibodies to measles, mumps, and rubella viruses are still detectable in 95-100%, 74-91%, and 90-100% of individuals respectively, 11 to 13 years after primary vaccination.
Clinical Studies: Clinical Efficacy: Efficacy of measles, mumps, and rubella vaccines was established in a series of double-blind controlled trials. These studies also established that seroconversion in response to vaccination against measles, mumps and rubella paralleled protection.
Immunogenicity: Clinical studies enrolling 284 triple seronegative children, 11 months to 7 years of age, demonstrated that subcutaneously administered M-M-R II vaccine is immunogenic. In these studies, a single subcutaneous injection of the vaccine induced measles HI antibodies in 95%, mumps neutralizing antibodies in 96%, and rubella HI antibodies in 99% of susceptible individuals.
A study of 6-month-old and 15-month-old infants born to mothers vaccinated with a measles vaccine in childhood, demonstrated that, following infant and toddler vaccination subcutaneously with Measles Virus Vaccine, Live (previously US-licensed, manufactured by Merck Sharp & Dohme LLC, Rahway, NJ, USA), 74% of the 6-month-old infants developed detectable neutralizing antibody titers while 100% of the 15-month-old infants vaccinated with Measles Virus Vaccine, Live or M-M-R II vaccine developed neutralizing antibodies. When the 6-month-old infants of immunized mothers were revaccinated at 15 months with M-M-R II vaccine, they developed antibody titers similar to those of toddlers who were vaccinated previously at 15-months of age.
In an open label clinical trial (NCT00432523) 752 children 12 through 18 months of age received M-M-R II either intramuscularly (n=374) or subcutaneously (n=378), concomitantly with VARIVAX. Antibody responses to measles, mumps, and rubella viruses were measured by ELISAs using sera obtained 6 weeks postvaccination. For anti-measles virus, anti-mumps virus and anti-rubella virus, seroresponse rates were defined as the percentage of children seronegative at baseline who achieved antibody titers above the respective seroresponse threshold for each assay 6 weeks post vaccination. Seroresponse thresholds were defined as 255 mIU/mL, 10 EU/mL, and 10 IU/mL for anti-measles virus, anti-mumps virus, and anti-rubella virus antibodies, respectively. For each vaccine antigen at least 89% of enrolled children were seronegative at baseline. In a post hoc analysis, seroresponse rates to mumps and rubella viruses were noninferior for the intramuscular group compared to the subcutaneous group (the lower bound of the 95% confidence interval for the difference in seroresponse rates [intramuscular group minus subcutaneous group] ≥-5%). While the seroresponse rate to measles virus narrowly missed meeting the post hoc criterion of -5% for noninferiority (lower bound of the 95% CI for the difference in seroresponse rate -5.28%), it met the pre-specified criterion using a -10% noninferiority margin. For measles, mumps and rubella antigens the lower bound of the 95% CI of the seroresponse rates was ˃90% after intramuscular administration. The point estimates of the proportions of children achieving antibody titers above the seroresponse thresholds for measles, mumps, and rubella viruses were as follows: 94.3%, 97.7%, and 98.1%, respectively, in the intramuscular group and 96.1%, 98.1%, and 98.1%, respectively, in the subcutaneous group.
Toxicology: Nonclinical Toxicology: Carcinogenesis, Mutagenesis, Impairment of Fertility: M-M-R II vaccine has not been evaluated for carcinogenic or mutagenic potential or impairment of fertility.