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Published on: June 26, 2020
Antibodies elicited by hepatitis E vaccination in humans confer cross-genus protection against rat hepatitis E virus
Zihao Chen1, Liqin Liu1, Jianwen Situ2
1State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, PR China; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, Fujian, PR China.
Background & Aims:
Paslahepevirus balayani (bHEV), also known as hepatitis E virus (HEV), encompasses eight genotypes, five of which infect humans. Rats are natural reservoirs of Rocahepevirus ratti genotype 1 (HEV-r-1; rat HEV; rHEV), which has recently been implicated in viral hepatitis. Despite the antigenic divergence between bHEV and rHEV, studies on shared protective antibodies remain rare.
Methods:
Polyclonal and monoclonal antibody responses against bHEV and rHEV were analyzed using antibody enzyme-linked immunosorbent assays. The efficacy of six potent bHEV-elicited cross-reactive antibodies in preventing rHEV infection was evaluated via challenge assays in rats. Cryo-electron microscopy was performed to assess the structural basis for the differential protective efficacy of the six antibodies. The viral lysis ability of these antibodies was assessed by separately reacting purified HEV-b-1 and HEV-r-1 virions with each antibody.
Results:
We determined that antibody responses to bHEV infection and vaccination possess limited cross-reactivity to rHEV and identified two cross-reactive antigenic sites within the E2s domain. Structural analysis and animal challenge studies pinpointed potent cross-reactive antibodies targeting antigenic site 1, indicating its prophylactic efficacy against rHEV. Conversely, antibodies recognizing antigenic site 2 were found to facilitate viral lysis of bHEV but not rHEV.
Conclusions:
These findings underscore the importance of antigenic site 1 in the design of broad-spectrum vaccines and therapeutics to mitigate the impact of diverse HEV genotypes on human health.
Impact And Implications:
Rat HEV (rHEV) spillover to humans represents an unprecedented threat. Significant antigenic differences between rHEV and bHEV (Paslahepevirus balayani) may exacerbate the impact of viral hepatitis. Our study reveals that cross-reactive human antibodies can offer protection against rHEV infection. Cross-protective antibodies targeting antigenic site 1 can be used to guide the development of practical strategies for preventing rHEV infection.
