Hepatitis E vaccine immunization for rabbits to prevent animal HEV infection and zoonotic transmission

Abstract

Hepatitis E virus (HEV) infection has become a significant global public health concern as increasing cases of acute and chronic hepatitis E are reported. HEV of animal origin was proved to be a possible source of human infection and a previous study showed that the recent licensed HEV 239 vaccine can serve as a candidate vaccine to manage animal sources of HEV infection. However, previous immunization strategy for rabbits was the same as that for human, which is too costly to conduct large-scale animal vaccination. In an effort to reduce the costs, three vaccination schemes were assessed in the present study. Forty specific pathogen-free (SPF) rabbits were divided randomly into five groups with eight animals for each and inoculated intramuscularly with different doses of HEV 239 and placebo, respectively. All animals were challenged intravenously with swine HEV-4 and rabbit HEV of different titers 7 weeks after the initial immunization and then fecal virus excretion was monitored for 10 weeks. The results indicated that immunizing rabbits with two 10μg doses of the vaccine is superior to vaccination with two 20μg doses or a single 30μg dose, which can protect rabbits against homologous and heterologous HEV infection. These findings could enable implementation of large-scale animal vaccination to prevent rabbit HEV infection and zoonotic transmission.

Cross‐genotype‐specific T‐cell responses in acute hepatitis E virus (HEV) infection

“…Recently, a recombinant HEV genotype 1 vaccine (Hecolin®) has been approved by the Chinese Food and Drug Administration in China . This vaccine induces HEV‐specific antibodies in 100% of vaccinated healthy individuals resulting in protection against homologous (genotype 1) and in part against heterologous (genotypes 2–4) HEV infections in humans and animal studies . The efficiency of protection is dependent on the antibody level prior HEV infection .…”

Experimental infection of rabbits with genotype 3 hepatitis E virus produced both chronicity and kidney injury

“…Liver and kidney tissues were collected from R1 for histopathology and immunohistochemistry. Detailed methods have been described previously 4. Positive/negative-stranded HEV RNA was detected in the kidneys, indicating virus replication in the tissue.…”

“…The healthy laboratory rabbit is easy to access and economic for use in large-scale experiments 4 5. Moreover, we have previously demonstrated that the rabbit is susceptible to HEV-44 5 and a 22-week chronic-type infection was observed when infected with a swine HEV-4 strain 4. Future experiments will determine the infectious dose that can establish stable chronic HEV-3 infection in the rabbit model and investigate whether rabbit model can also be used to study chronic infection with HEV-4.…”

Development and validation of a new serum standard for the measurement of anti‐HEV antibodies in animals

“…A WHO reference standard for anti‐HEV antibody (NIBSC ref 95/584, 100 IU/ml) [Ferguson et al, ] was provided by Wantai Biopharmaceutical, Inc. (Beijing, China). The candidate anti‐HEV antibody serum RS26 (rabbit serum 26 as the standard serum in this study) was collected from a rabbit vaccinated with two 20 µg doses of HEV 239 vaccine at week 0 and 4 [Zhang et al, ]. These and all other sera were tested for the presence of anti‐HEV antibody with a commercial HEV‐specific sandwich ELISA assay as previously described [Wang et al, ; Liu et al, ].…”