Abstract
Hepatitis E virus (HEV) constitutes a significant health burden worldwide, with an estimated approximately 33% of the world’s population exposed to the pathogen. The recent licensed HEV 239 vaccine in China showed excellent protective efficacy against HEV of genotypes 1 and 4 in the general population and pregnant women. Because hepatitis E is a zoonosis, it is also necessary to ascertain whether this vaccine can serve to manage animal sources of human HEV infection. To test the efficacy of the HEV 239 vaccine in protecting animal reservoirs of HEV against HEV infection, twelve specific-pathogen-free (SPF) rabbits were divided randomly into two groups of 6 animals and inoculated intramuscularly with HEV 239 and placebo (PBS). All animals were challenged intravenously with swine HEV of genotype 4 or rabbit HEV seven weeks after the initial immunization. The course of infection was monitored for 10 weeks by serum ALT levels, duration of viremia and fecal virus excretion and HEV antibody responses. All rabbits immunized with HEV 239 developed high titers of anti-HEV and no signs of HEV infection were observed throughout the experiment, while rabbits inoculated with PBS developed viral hepatitis following challenge, with liver enzyme elevations, viremia, and fecal virus shedding. Our data indicated that the HEV 239 vaccine is highly immunogenic for rabbits and that it can completely protect rabbits against homologous and heterologous HEV infections. These findings could facilitate the prevention of food-borne sporadic HEV infection in both developing and industrialized countries.
Highlights
Hepatitis E virus (HEV) constitutes a significant health burden worldwide, especially in regions with poor sanitation including large parts of Asia, Africa and Mexico, where it has proved to be the most or second-most important cause of acute clinical hepatitis [1]
We evaluated the efficacy of the HEV 239 vaccine in protecting rabbits against homologous and heterologous HEV infections, aiming to examine whether HEV 239 could serve to manage HEV transmission from its animal reservoirs
Protection against HEV infection in vaccinated rabbits following virus challenge At week 6, each of the rabbits in groups A was challenged with 2.56106 copies of a rabbit HEV strain and those in group B with the same dose of a swine HEV strain of genotype 4.The course of the infection was monitored for 10 weeks after challenge by measuring serum ALT levels, viremia, fecal shedding and HEV antibody responses
Summary
Hepatitis E virus (HEV) constitutes a significant health burden worldwide, especially in regions with poor sanitation including large parts of Asia, Africa and Mexico, where it has proved to be the most or second-most important cause of acute clinical hepatitis [1]. To-date, in addition to human, mammalian HEV strains have been isolated from both domesticated and wild pigs, sika deer, mongooses and rabbits, and antibodies to HEV have been detected in a wider range of animal species including cats, dogs, cattle, sheep, goats, horses, macaques, donkeys, rats, and mice [3,4]. The higher frequency of antibodies to HEV among animal handlers [9,10] and the close genetic relationship of HEV strains obtained from humans and those from swine in the same geographical regions support zoonotic transmission is a significant route of the virus spreading [11,12]. The zoonotic nature of HEV dictates that foodborne infection can possibly be prevented through vaccination of significant animal reservoirs such as pigs and rabbits
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