Neutralizing antibody titers against Hantavirus differ significantly between historical vaccine strains and representative circulating epidemic strains in China, according to a comparative evaluation of convalescent patient and vaccinee sera. The investigation assessed whether viral divergence across rodent reservoirs influences the humoral immunity elicited by long-standing immunization programs.
Hemorrhagic fever with renal syndrome (HFRS), caused by Hantavirus, continues to present a significant public health burden globally. In key endemic provinces throughout China, prevention efforts have relied on a bivalent inactivated vaccine formulated with Hantaan virus (HTNV) and Seoul virus (SEOV) strains originally isolated two decades ago.
Following decades of comprehensive control measures, HFRS incidence in China has transitioned into a phase of low-level epidemic fluctuation. Nevertheless, ongoing viral transmission within wild rodent host populations can spur dynamic shifts in genetic diversity and immunogenicity, creating uncertainty regarding ongoing vaccine-induced protection and underlying pathogenic mechanisms.
To evaluate these immune responses, researchers established a serum panel comprising convalescent samples from clinical HFRS cases alongside specimens from individuals who received standardized immunization with the bivalent inactivated vaccine. Using an enzyme-linked immunosorbent assay-based microneutralization test (MN-ELISA), neutralizing antibody titers were measured against the HTNV vaccine strain 84FLi, the SEOV vaccine strain L99, and three representative epidemic strains representing distinct genotypes: HTNV strain SX26 and SEOV strains LN03 and FJ-17.
Hantavirus-neutralizing antibodies were successfully detected across all tested serum samples. Among the 48 evaluated HFRS patients, laboratory identification categorized 47.92 percent (23 of 48) as HTNV infections, 27.08 percent (13 of 48) as SEOV infections, and 25 percent (12 of 48) as untypable cases.
Titers against vaccine strains and circulating epidemic strains exhibited pronounced divergence. For HTNV, both convalescent patient sera and vaccinee sera demonstrated significantly higher geometric mean titers against the vaccine strain 84FLi compared to the epidemic strain SX26, registering 1:386.08 versus 1:223.04 (P
In contrast, the pattern reversed for SEOV strains. Patient sera displayed significantly lower geometric mean titers against the L99 vaccine strain than against the epidemic strain LN03, at 1:177.02 versus 1:297.71 (P
The study authors concluded that Hantavirus genetic diversity and immunogenicity exhibit defined geographical characteristics. Although the current bivalent vaccine stimulates broad neutralizing antibodies and infection confers cross-reactive responses across genotypes, variations in neutralizing efficacy against circulating strains highlight the necessity of continuous regional genomic surveillance and routine evaluation of vaccine matching.
The study provides critical nuance regarding how cross-neutralization functions across divergent viral genotypes. While the bivalent inactivated vaccine used in China induces broad neutralizing antibodies, its cross-protective efficacy can vary when challenged by different circulating strains and genotypes. Natural infection with Hantavirus similarly generates cross-neutralizing antibodies whose titers differ significantly depending on the genotype involved, yet still succeed in conferring sufficient cross-protection. Furthermore, the significant immunogenicity heterogeneity identified between the two Seoul virus epidemic strains, LN03 and FJ-17, demonstrates that circulating field isolates from the same virus species can exhibit disparate antigenic properties compared to the historical L99 vaccine strain isolated two decades ago.
These shifting antigenic profiles are deeply connected to the natural reservoir dynamics of the pathogen. Although decades of comprehensive prevention and control measures have successfully brought hemorrhagic fever with renal syndrome to a stage of low-level epidemic fluctuation in China, continuous viral transmission among rodent host animals persists. This sustained animal-reservoir circulation can drive dynamic changes in the genetic diversity and immunogenicity of Hantavirus. In turn, such shifts have the potential to influence viral pathogenic mechanisms and diminish the protective effectiveness of established vaccines, making timely monitoring and evaluation of viral immunogenicity an indispensable priority.
To sustain epidemic control, the study underscores several critical surveillance and public health priorities. The authors highlight the great significance of strengthening surveillance of the genetic characteristics of regional-specific circulating viral strains. In parallel, public health programs must regularly evaluate the matching degree between vaccine protective effectiveness and currently circulating epidemic strains. These coordinated efforts are necessary to predict and evaluate the transmission and pathogenic risks posed by evolving Hantavirus strains, thereby providing the evidence needed to timely optimize prevention and control strategies and measures across endemic regions.
Subject of Research: Comparative neutralizing antibody evaluation of Hantavirus vaccine and epidemic strains in China
Article Title: Immunogenicity of Hantavirus and evaluation of vaccine protective efficacy: A comparative neutralizing antibody study of vaccine strains and representative epidemic strains from selected provinces in China
Article References: Huang, X., Zheng, Z., Du, S., Li, A., Tian, F., Gu, T., Zheng, L., Chuan, L., Wang, Q., Yuan, L., & Li, J. (2026). Immunogenicity of Hantavirus and evaluation of vaccine protective efficacy: A comparative neutralizing antibody study of vaccine strains and representative epidemic strains from selected provinces in China. PLOS Neglected Tropical Diseases, 20(11), e0014811. https://doi.org/10.1371/journal.pntd.0014811
Image Credits: AI Generated
DOI: 10.1371/journal.pntd.0014811
Keywords: Hantavirus, Hemorrhagic fever with renal syndrome, Hantaan virus, Seoul virus, HFRSbiv, bivalent inactivated vaccine, neutralizing antibodies, microneutralization test, MN-ELISA, 84FLi, L99, SX26, LN03, FJ-17, geometric mean titer, rodent host animals, viral immunogenicity, cross-protection