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Immunogenicity and protective efficacy in rhesus monkeys of a recombinant ORF2 protein from hepatitis E virus genotype 4

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Abstract

Several antigens derived from hepatitis E virus (HEV) genotype 1 strains have shown immunogenicity and efficacy against hepatitis E in primates and humans. However, the protective effect of a vaccine derived from HEV genotype 4 has not been studied. This study aimed to evaluate the immunogenicity and protective efficacy of the T1-ORF2 (56 kDa) capsid protein derived from HEV strain T1 (genotype 4) in rhesus monkeys. Two doses (40 μg) of alum-absorbed T1-ORF2 capsid protein were administered 4 weeks apart. Seroconversion occurred in all immunized monkeys 1–2 weeks after the first dose. The peak levels of anti-HEV IgG appeared at 2–3 weeks after the second dose and ranged from 5.7 to 196.0 U/ml. All monkeys showed an anamnestic antibody response to the second dose. Control monkeys immunized with saline remained negative for HEV antibodies throughout the pre-challenge period. The immunized monkeys were challenged intravenously with HEV genotypes 1 and 4. Monkeys immunized with T1-ORF2 were protected from infection and hepatitis after challenge with 5 × 104 genome equivalents of HEV, regardless of the genotype. After challenge with 5 × 105 genome equivalents of HEV genotype 4, the monkeys immunized with T1-ORF2 had a shorter period of raised alanine aminotransferase levels and a shorter duration of fecal shedding compared to control monkeys immunized with saline. In conclusion, these results suggest that, in rhesus monkeys, the T1-ORF2 capsid protein of HEV genotype 4 has similar cross-protective effects to other candidate vaccines derived from HEV genotype 1.

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Acknowledgments

We thank Dr. Mi Zhou Hui, from AmProtein Inc. Camarillo, CA, USA (www.amprotein.com) for technical support, especially for expressing and purifying the ORF2 protein used in this study and providing the lyophilized purified ORF2 protein. This study was supported by the “863” project (grant: 2006AA02Z453) from the Ministry of Science and Technology, China.

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Authors and Affiliations

  1. Department of Cell Biology, National Institute for the Control of Pharmaceutical and Biological Products, No. 2 Tiantanxili, Chongwen District, 100050, Beijing, China

    W. J. Huang, H. Y. Zhang, H. Y. Lan & Y. C. Wang

  2. Division of Medicine, University College London, Windeyer Building, 46 Cleveland Street, London, W1T 4JF, UK

    T. J. Harrison

  3. Department of Virology, Center of Disease Control in Guangxi Autonomous Regions, Guanxi Nanning, China

    G. Y. Huang

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  1. W. J. Huang
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  2. H. Y. Zhang
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  6. Y. C. Wang
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Correspondence to Y. C. Wang.

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Huang, W.J., Zhang, H.Y., Harrison, T.J. et al. Immunogenicity and protective efficacy in rhesus monkeys of a recombinant ORF2 protein from hepatitis E virus genotype 4. Arch Virol 154, 481–488 (2009). https://doi.org/10.1007/s00705-009-0335-7

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  • DOI: https://doi.org/10.1007/s00705-009-0335-7

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