Immunogenicity and safety of an interchangeable vaccination schedule of two inactivated Japanese encephalitis vaccines: a multicentric, phase IV, open-label, randomized controlled trial
In brief
Mixing Japanese encephalitis vaccines produced about 90% antibody response in infants
In a randomized trial of 911 infants, mixed-brand vaccine schedules produced seroconversion in about 90%, similar to schedules using the same vaccine twice. Reported adverse events were also similar across groups, and no serious event was judged vaccine related. The results support flexibility when children switch products, but address short-term antibody response, not long-term protection against disease.
- Journal
- EClinicalMedicine (Q1)
- Published
- 22 September 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Jeromie Wesley Vivian Thangaraj, Himabindu Reddy, Gajanan N Sapkal, Saravana Kumar Velusamy, Manish A Jain, Bhagirathi Dwibedi, et al.
- PMID
- 42893108
- DOI
- 10.1016/j.eclinm.2026.104235
Why clinicians should know about it
- Picked for Immunology and Allergy (top studies of the week, 1 November 2026): Phase IV non‑inferiority RCT of mixed JE vaccine schedule
Abstract
BACKGROUND: In India, two inactivated Japanese encephalitis (JE) vaccines, JENVAC and JEEV, are used in childhood immunization program as a two-dose schedule. Vaccine supply interruptions and population mobility can result in children receiving different products for their first and second doses. We assessed immunogenicity and safety of mixed-product vaccine schedules. METHODS: In this multicentric, open-label, phase 4, non-inferiority randomized trial conducted during November 11, 2023-September 2, 2025, infants aged 9-12 months were assigned (1:1:1:1) to JENVAC-JEEV, JENVAC-JENVAC, JEEV-JENVAC, or JEEV-JEEV. Second dose was given at the age of 16-24 months. The primary outcome was seroconversion assessed by 50% plaque reduction neutralization test titer against wild-type JE virus 28 days after dose-2. The secondary outcomes included frequency of solicited and unsolicited adverse events, and serious adverse events following JE vaccine schedules. Non-inferiority was concluded if the lower bound of the 95% CI for difference in seroconversion proportion between the mixed and same-product vaccine schedule exceeded -10% and was less than 0%. Registered with Clinical Trials Registry-India (CTRI/2023/07/055155). FINDINGS: Between November 11, 2023, and June 8, 2024, 911 infants were randomly assigned (1:1:1:1) to JENVAC-JEEV (n = 228), JENVAC-JENVAC (n = 228), JEEV-JENVAC (n = 227), and JEEV-JEEV (n = 228). In modified intention-to-treat analysis, seroconversion after second dose was 89.8% (194/216), 90.2% (184/204), 90.9% (189/208), and 89.2% (190/213) respectively. The difference in seroconversion between mixed-product and same-product vaccine schedules was -0.38% (95% CI -6.1 to 5.4) among JENVAC-primed and 1.66% (-4.1 to 7.4) among JEEV-primed infants. The corresponding estimates in per-protocol analysis were -1.11% (95% CI -6.7 to 4.5) and 0.89% (-4.9 to 6.6) respectively. Solicited adverse events occurred in 35.5-37.9% infants across the study groups. None of the serious adverse events was vaccine related. INTERPRETATION: Mixed-product JENVAC and JEEV schedules were non-inferior to same-product schedules for short-term neutralizing antibody seroconversion and showed no safety signals. These findings support programme flexibility when children cannot complete JE vaccination with the same-product. FUNDING: The trial was funded by Indian Council of Medical Research, New Delhi, India.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.