The trivalent combined measles, mumps, and rubella (MMR) vaccine is widely used in many countries, and in Japan, MMR vaccines that each use 1 of 3 mumps strains were introduced in 1989; however, these were discontinued after 1993 because of a high and unexpected incidence of aseptic meningitis. There is no MMR vaccine currently available in Japan, but 2 doses of a bivalent measles rubella (MR) vaccine are recommended to citizens as of 2006. Authors of a study published in the Journal of Infection and Chemotherapy report findings on a clinical trial that assessed the safety and immunogenicity of JVC-001 (Japan Vaccine Co Ltd, Daiichi Sankyo) administered as a second dose to children in Japan.
For this open-label, multicenter, single-arm, phase 3 study, healthy children from Japan aged 5 to 6 years were enrolled. Prior to vaccine administration, the investigators collected blood samples for antibody titer determination, which were measured prior to the second dose to confirm sustained immunity to the initial MR vaccine, mumps vaccine, and JVC-001. A single 0.5-mL dose of JVC-001 was administered subcutaneously or intramuscularly on visit 1 (or day 1), and on days 8, 15, and 29, participants’ health was checked via phone or email. On day 42, participants attended their second visit and blood samples were again collected.
The enrolled participants received 1 dose of the JVC-001 MMR vaccine or 1 dose each of an MR and mumps vaccine when aged 1 to less than 4 years, had a surrogate who was able to comply with all protocol-specified schedules and procedures, and were judged by the study investigators to be “sufficiently healthy” for participation. Exclusion criteria included the following: serious acute illness or a body temperature of 37ºC at the time of eligibility; a disease that hinders the immune function or receipt of immunosuppressive drugs for more than 2 consecutive weeks within the past 6 months; a known diagnosis of immunodeficiency; if the participant or family member was suspected to have either measles, mumps, or rubella; or a history of chickenpox within 30 days or a history of viral disease within 15 days prior to providing consent.
Key Takeaways
- High Seroprotection and Seroresponse Rates: The phase 3 study of the JVC-001 vaccine in Japanese children demonstrated 100% seroprotection rates against measles, rubella, and mumps. Additionally, all participants who were seronegative for mumps before the second vaccination achieved a 100% seroresponse rate, indicating strong immunogenicity.
- Adverse Drug Reactions and Safety Profile: Approximately 40% of participants reported adverse drug reactions (ADRs), with most being mild in severity. The most common injection site ADR was erythema, and pyrexia was the only solicited systemic ADR. The study also noted that nearly half of the participants experienced treatment-emergent adverse events, with infections and infestations being the most common.
- Study Limitations and Future Research Needs: The study’s limitations included its short duration, the small number of participants who had received the initial JVC-001 vaccination, and the single-arm design, which prevented comparisons with other vaccines. The authors suggest that future studies could address these limitations to further validate the findings.
A total of 100 participants completed the study, of which 20% were participants in the previous phase 1/2 study of JVC-001. The mean ± SD days since prior vaccination was 1618.2 ± 154.8 for MR vaccination, and 1583.7 ± 186.9 for mumps vaccination.
According to the findings, the seroprotection rate of antibody titers against measles, rubella, and mumps virus (genotype D) were 100.0% (95 % confidence interval [CI] 96.4%, 100.0%), 100.0% (95% CI 96.4 %, 100.0%), and 100.0% (95 % CI 96.3%, 100.0%), respectively. Additionally, the seroresponse rate of antibody titers to mumps virus on day 43 was 100% (95 % CI 47.8%, 100.0%) in all 5 participants who were seronegative for the mumps virus prior to the second vaccination. Geometric mean titer increases from day 1 to 43 were 16.0 to 55.7 for measles, 35.5 to 99.0 for rubella, and 25.7 to 89.5 for mumps.
Additionally, adverse drug reactions (ADRs) were reported by approximately 40% of participants, 34% experienced solicited injection site ADRs, and 13% solicited systemic ADRs. Among the solicited injection site ADRs, erythema was the most common (24%) with pyrexia being the only solicited systemic ADR (13%). According to the investigators, most ADRs were mild in severity, with only 1 incidence of a severe ADR, which was pyrexia.
Further, approximately 48% of participants experienced a treatment-emergent adverse event, with infections and infestations being the most common (24%). Of these, the most frequently reported were nasopharyngitis (8%) and gastroenteritis (6%). Respiratory, thoracic, and mediastinal disorders in addition to skin and subcutaneous tissue complications were also considered to be common (10% each), along with administration site conditions (9%).
Potential limitations of the study include the duration (43 days), the number of participants who had received an initial vaccination with JVC-001, and the study’s single-arm design which did not allow the investigators to compare different vaccines for the second MMR vaccination. The investigators note that other studies can explore these areas further.
Reference
Nakayama T, Kawamura A, Sogawa Y, et al. Phase III, open-label, single-arm study of a new MMR vaccine (JVC-001); measles AIK-C, mumps RIT 4385, rubella Takahashi, as a second vaccine dose in healthy Japanese children aged 5–6 years. JIC. 2024. doi:10.1016/j.jiac.2024.06.011
