Immunogenicity of a single fractional intradermal dose of Japanese encephalitis live attenuated chimeric vaccine

Abstract

Abstract Background Japanese encephalitis (JE) is endemic in Asia and the western Pacific. Vaccination is recommended for travellers to endemic regions, but the high cost of the vaccine is a major barrier to uptake. Methods A quasi-experimental, pre-post intervention clinical trial without a control group was conducted to assess the immunogenicity and safety of intradermal (ID) JE vaccine. Healthy adults (18–45 years) received one dose of 0.1 mL (20% of standard dose) ID Imojev® (JE live attenuated chimeric vaccine, Sanofi-Aventis). Adverse events following immunization (AEFIs) were recorded 10 days post-vaccination. Blood samples were collected at baseline, 4 and 8 weeks post-vaccination. Neutralizing antibodies were measured using 50% plaque reduction neutralization test (PRNT50). Seroconversion was defined as PRNT50 titre ≥10. An in vitro study was also conducted to quantify the rate of decay of vaccine potency after reconstitution. Results In total, 51 participants (72.6% females, median age 31 years), all non-reactive to JE virus at baseline were enrolled. Mild and moderate AEFIs were reported by 19.6% of participants; none required medical attention or interfered with normal daily activities. All participants seroconverted at 4 weeks (GMT 249.3; 95%CI:192.8–322.5) and remained seropositive at 8 weeks (GMT 135.5; 95%CI:104.5–175.6). Vaccine potency declined at a rate of 0.14 log plaque-forming units/0.5 mL per hour. Conclusions In healthy adults, a single 0.1 mL ID dose of Imojev was safe and immunogenic, at least in the short term. Reconstituted vials of Imojev vaccine may not retain their potency after 6 hours. Fractional JE ID vaccination could be a cheaper yet effective alternative for short-term travellers. Further studies need to investigate the immune response in a wider age range of individuals and the long-term immunogenicity of fractional JE ID vaccines. Clinical trials registration ACTRN12621000024842.