A double blind, randomized, active controlled study to assess the safety, tolerability and immunogenicity of measles, mumps rubella, and varicella vaccine (MMRV) manufactured using an alternative process

Abstract

Vaccination against measles, mumps, rubella, and varicella is recommended for all children in the US. Limitations manufacturing Oka/Merck strain varicella-zoster virus have hampered the availability of the combination vaccine (MMRV) against these 4 viruses, which drove the need to investigate an alternative manufacturing process. Healthy children 12-to-23 months of age at 71 US sites were randomized (1:1) to receive MMRV manufactured using an alternative process (MMRV_AMP) or the currently licensed MMRV. Subjects received 2 0.5 mL doses 3 months apart. Sera were collected before and 6 weeks after Dose-1. Adverse experiences (AEs) were collected for 42 d after each dose and serious AEs and events of special interest for 180 d after Dose-2. Overall, 706 subjects were randomized to MMRV_AMP and 706 to MMRV and 698 and 702 received at least 1 dose of study vaccine, respectively. The risk difference in response rates and geometric mean concentrations of antibody to measles, mumps, rubella, and varicella viruses 6 weeks after Dose-1 met non-inferiority criteria for MMRV_AMP versus, MMRV. Response rates met acceptability criteria for each virus, and the seroconversion rate to varicella-zoster virus was 99.5% in both groups. Vaccine-related AEs were mostly mild-to-moderate in intensity and somewhat more common after MMRV_AMP. Febrile seizures occurred at similar rates in both groups during the first 42 d after each vaccine dose. MMRV_AMP is non-inferior to MMRV and represents an important advancement in maintaining an adequate supply of vaccines against these diseases.

Keywords: MMRV; immunogenicity; measles; mumps; rubella; safety; varicella.

Figure 1.

Subject disposition. ^aNumber of subjects excluded from the per-protocol MMRV_AMP postdose 1 immunogenicity analyses: Measles (69); Mumps (80); Rubella (90); and Varicella (112). ^bNumber of subjects excluded from the per-protocol MMRV postdose 1 immunogenicity analyses: Measles (81); Mumps (92); Rubella (109); and Varicella (114). ^cOne subject did not receive Dose 2, but was followed for 180 d postdose 1 and discontinued due to an AE (onset was Day 5 postdose 1) during the extended safety follow-up but before study completion.

Figure 2.

Average daily temperature (°F) days 1 to 42.