Immunogenicity and Safety of a Measles-Mumps-Rubella Vaccine Administered as a First Dose to Children Aged 12 to 15 Months: A Phase III, Randomized, Noninferiority, Lot-to-Lot Consistency Study

Abstract

Background MMR II (M-M-R II [Merck & Co, Inc.]) is currently the only measles, mumps, and rubella (MMR) vaccine licensed in the United States. A second MMR vaccine would mitigate the potential risk of vaccine supply shortage or delay. In this study, we assessed the immunogenicity and safety of another MMR vaccine (MMR-RIT [Priorix, GlaxoSmithKline]) compared with those of the MMR II in 12- to 15-month-old children who received it as a first dose. Methods In this phase III, observer-blinded, noninferiority, lot-to-lot consistency clinical trial (ClinicalTrials.gov identifier NCT01702428), 5003 healthy children were randomly assigned to receive 1 dose of MMR-RIT (1 of 3 production lots) or MMR II along with other age-recommended routine vaccines. We evaluated the immunogenicity of all vaccines in terms of antibody concentrations (by using an enzyme-linked immunosorbent assay or electrochemiluminescence assay) and/or seroresponse rates 43 days after vaccination. We also assessed the reactogenicity and safety of the vaccines. Results Immunoresponses after vaccination with MMR-RIT were robust and noninferior to those after vaccination with the MMR II. Immunogenicity of the 3 production lots of MMR-RIT was consistent; more than 97% of the children had a seroresponse to MMR components. The coadministered vaccines elicited similar immunoresponses in the MMR-RIT and MMR II groups. Both MMR vaccines resulted in comparable reactogenicity profiles, and no safety concerns were detected. Conclusions If licensed, the MMR-RIT could provide a valid option for the prevention of measles, mumps, and rubella in children in the United States and would reduce potential risks of a vaccine shortage.

Evaluation of the Safety and Immunogenicity of M-M-RII (Combination Measles-mumps-rubella Vaccine)

“…In 3 studies in children 12-15 months of age that assessed seroconversion 42 days postvaccination in the same laboratory using the same assays, the response rates for each of the 3 antigens were remarkably similar (96.3%-98.0% for measles, 97.6%-97.9% for mumps and 98.3-98.5% for rubella). 19,20,23 Postvaccination measles seropositivity of subjects 4-7 years old was 99.3%-100%, with 100% of participants in this age range seropositive for mumps and rubella. In participants ≥7 years of age, the postvaccination seropositivity rates for MMR were 96.0-99.1%, 64.0%-100% and 99.8%-100%, respectively.…”

“…M-M-RII was found not to impair the immunogenicity of vaccines against varicella, hepatitis A, diphtheria, tetanus, pertussis, polio, pneumococcal pneumonia or Japanese encephalitis. [21][22][23][24]27…”

Mumps Outbreaks in Vaccinated Populations—Is It Time to Re-assess the Clinical Efficacy of Vaccines?

“…Mumps-specific antibodies have been detected 1-2 years postvaccination and without substantial decline for 8 years after mumps vaccination, with the immunogenicity and efficacy of the MMR vaccine showing comparable immunogenicity levels to post-vaccination levels at 3 years (148,156). However, most studies of this vaccine (involving either a mumps-specific vaccine or a combined vaccine) only followed-up to 30-56 days postvaccination (157)(158)(159)(160)(161)(162)(163)(164)(165)(166)(167). Despite few follow-up studies estimating post-vaccination antibody titers specific to the vaccine mumps strain, the evidence of seroconversion post-vaccination in a number of studies indicate that primary vaccine failure does not seem to be a significant contributor to the outbreaks that have been recently observed (118,149,150,152,158,(168)(169)(170)(171).…”

Measles, the need for a paradigm shift

“…Other case-control studies have provided divergent data from different world areas: MCV immunogenicity was 80% (95% CI [60-90%]) in Bangladesh [57], whereas it was 96.7% (95% CI [94.5-98%]) for one dose and 99.7% (95% CI [99.2-99.9%]) for two doses in Australia [58]. Randomized trials have assessed MCV efficacy through antibody concentrations [59][60][61][62][63][64][65][66][67][68][69] or non-specific effects on all-cause mortality, hospitalization, and growth in low-income countries paediatric populations [70][71][72]. Essentially, there have been no trials evaluating the clinical efficacy of MCV schedules in preventing measles disease or monitoring the long-term quality of the immune response [51].…”

“…Additionally, the quality of vaccines or incorrect documentation of first and/or second dose vaccination must be considered. Notably, in Iran, two distinct Edmonstonbased MCV showed differences in immunogenicity in the first years of life [92], whereas in American randomized trials (Table 1), the MMR-RIT vaccine (Priorix, GlaxoSmithKline) had a sero-response rate and safety profile equivalent to the only licensed MMR vaccine in the United States (MMR-II, Merck&Co Inc.) [64,65].…”