Genotype III-based Japanese encephalitis vaccines exhibit suboptimal neutralizing response to re-emerging genotype V 2915

Abstract Description Japanese encephalitis (JE) has been predominantly controlled through vaccination. However, the isolation of JE virus (JEV) genotype V (GV) in China in 2009, and the subsequent alarming increase in JE cases in the Republic of Korea since 2010, present a new challenge. Serum from immunocompromised pediatric patients vaccinated with an inactivated JE vaccine showed higher 50% plaque reduction neutralization test (PRNT50) geometric mean titer (GMT) against GIII Nakayama (11,358; 95% CI = 1,790, 29,658), but lower GMTs against GV isolates: GV Muar (499; 95% CI = 0, 2,437), GV 43279 (308; 95% CI = 159, 582), and GV 43413 (231; 95% CI = 108, 738). Similarly, 32 healthy volunteers receiving a live attenuated JE vaccine achieved 100% seroprotection against GIII Nakayama with GMT of 338 (95% CI = 304, 651) at 1 month post-vaccination. However, GMTs against GV isolates were 123 (95% CI = 102, 446) for GV Muar, 81 (95% CI = 63, 168) for GV 43279, and 107 (95% CI = 100, 322) for GV 43413, not achieving 100% seroprotection against these isolates. At 6 months post-vaccination, GMT against Nakayama increased to 696 (95% CI = 409, 2,353), while remaining similar for GV isolates. Our study underscores that current GIII-based vaccines do not provide comparable protection against GV JEVs, impacting individuals in both current and potential endemic regions, as well as travelers to these regions. Funding Sources This work was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea [RS-2024-00335717] and the National Institute of Health (NIH), Republic of Korea [2024ER170100]. Topic Categories Vaccines and Immunotherapy (VAC)