Genotype III-Based Japanese Encephalitis Vaccines Exhibit Diminished Neutralizing Response to Re-emerging Genotype V

Ah-Ra Lee; Woo-Jin Kim; Haeyoun Choi; Sang-Hyun Kim; Su-Yeon Hong; Sang-Mu Shim; Hee Il Lee; Jae Min Song; Seong-Jun Kim; Tomohiro Ishikawa; Ji-Man Kang; Hyeon-Seok Eom; Sang-Uk Seo

doi:10.1093/infdis/jiae589

Genotype III-Based Japanese Encephalitis Vaccines Exhibit Diminished Neutralizing Response to Re-emerging Genotype V

J Infect Dis. 2024 Nov 22:jiae589. doi: 10.1093/infdis/jiae589. Online ahead of print.

Authors

Ah-Ra Lee^{1

2}, Woo-Jin Kim^{1

2}, Haeyoun Choi², Sang-Hyun Kim^{1

2}, Su-Yeon Hong^{1

2}, Sang-Mu Shim³, Hee Il Lee⁴, Jae Min Song⁵, Seong-Jun Kim⁶, Tomohiro Ishikawa⁷, Ji-Man Kang⁸, Hyeon-Seok Eom⁹, Sang-Uk Seo^{1

2}

Affiliations

¹ Department of Medical Sciences, Graduate School of The Catholic University of Korea, Seoul, Republic of Korea.
² Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
³ Division of Acute Virus Diseases, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Republic of Korea.
⁴ Division of Vectors and Parasitic Diseases, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Republic of Korea.
⁵ School of Biopharmaceutical and Medical Sciences, Sungshin Women's University, Seoul, Republic of Korea.
⁶ Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
⁷ Department of Microbiology, Dokkyo Medical University School of Medicine, Tochigi, Japan.
⁸ Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
⁹ Department of Hematology-Oncology, Center for Hematologic Malignancy, National Cancer Center, Goyang, Republic of Korea.

PMID: 39574290
DOI: 10.1093/infdis/jiae589

Abstract

Background: 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.

Methods: Serum samples from individuals vaccinated with genotype III (GIII)-based JE vaccines were analyzed for neutralizing seroresponse to GV isolates.

Results: 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.

Conclusions: 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.

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