Immunogenicity and safety of a second dose of a measles-mumps-rubella vaccine administered to healthy participants 7 years of age or older: A phase III, randomized study

Abstract

The introduction of vaccination programs against measles, mumps, and rubella (MMR) led to significant global reduction in morbidity and mortality from these diseases. The currently recommended MMR vaccination schedule in the United States of America comprises 2 vaccine doses typically administered at 12-15 months and 4-6 years, respectively. Considering recent outbreaks in the USA, catch-up vaccination with an additional dose of MMR vaccine could contribute to outbreak control and community protection. This phase III, observer-blind, randomized controlled trial (NCT02058563) assessed the immunogenicity and safety of a dose of the MMR-RIT vaccine (Priorix, GSK) compared to MMR II vaccine (control; M-M-R II, Merck&Co Inc.) in ≥7-year-olds who had received ≥1 previous dose of MMR vaccine. We assessed anti-measles, anti-mumps, and anti-rubella antibody geometric mean concentrations (GMCs; primary endpoint) and seroresponse rates (SRRs) at day 42 post-vaccination. Solicited, unsolicited, and serious adverse events (AEs) were recorded. The according-to-protocol cohort for immunogenicity included 869 participants (MMR-RIT: N = 433; MMR II: N = 436). We observed anti-measles, anti-mumps, and anti-rubella antibody GMCs of 1790.2 mIU/mL, 113.5 EU/mL, and 76.1 IU/mL, respectively, and SRRs of 98.8%, 98.4%, and 99.5%, respectively, after a dose of MMR-RIT; non-inferiority compared to MMR II was demonstrated. Both vaccines showed comparable reactogenicity profiles; the most common solicited AEs were injection site redness and pain, and fever (MMR-RIT: 12.2%, 11.8%, and 3.0%; MMR II: 11.7%, 11.5%, and 5.2%, respectively). The dose of MMR-RIT induced robust immune responses that were not inferior to those of MMR II, and was well tolerated.

Keywords: immunization schedule; immunogenicity; measles-mumps-rubella vaccine; safety; second dose.

Figure 1.

Focus on the Patient section.

Figure 2.

Flow diagram of the study participants. Footnote: N, number of participants; n, number of participants within the category; GCP, good clinical practice; TVC, total vaccinated cohort; ATP, according-to-protocol.

Figure 3.

Percentage of participants who achieved a 4-fold or greater increase in anti-measles, anti-mumps, or anti-rubella virus antibody concentrations at Day 42 (ATP cohort for immunogenicity). Footnote: N, number of participants with both pre- and post-vaccination available results; ATP, according-to-protocol. For participants with a seronegative status at pre-vaccination, a 4-fold rise in antibody concentration is defined as 4 times the cut-off level of the assay. Cut-off levels for anti-measles, anti-mumps and anti-rubella virus antibody concentrations are 150 mIU/mL, 5 EU/mL and 4 IU/mL, respectively. The error bars represent the upper and lower limits of the two-sided 95% confidence intervals obtained using the Clopper Pearson method.

Figure 4.

Incidence of solicited injection site (Day 0–3) and general adverse events (Day 0–42) (total vaccinated cohort). Footnote: N, number of participants with the documented dose with local symptoms sheets completed *Except for pain, redness, and swelling, for which MMR-RIT (N = 433). Fever: temperature ≥38°C. Grade 3 was defined as: limb was painful at rest, which prevented normal everyday activities (pain); diameter >50 mm (redness and swelling); temperature >39.5°C (fever); adverse event preventing normal, everyday activities (joint pain, rash/exanthem, meningism/seizure); swelling with accompanying general symptoms (parotid/salivary gland swelling). The error bars represent the upper and lower limits of the two-sided 95% confidence intervals obtained using the Clopper Pearson method.

Figure 5.

Study design. Footnote: AEs, adverse events; SAEs, serious adverse events.