Prior infection of pigs with a genotype 3 swine hepatitis E virus (HEV) protects against subsequent challenges with homologous and heterologous genotypes 3 and 4 human HEV

Abstract

Hepatitis E virus (HEV) is an important human pathogen. At least four recognized and two putative genotypes of mammalian HEV have been reported: genotypes 1 and 2 are restricted to humans whereas genotypes 3 and 4 are zoonotic. The current experimental vaccines are all based on a single strain of HEV, even though multiple genotypes of HEV are co-circulating in some countries and thus an individual may be exposed to more than one genotype. Genotypes 3 and 4 swine HEV is widespread in pigs and known to infect humans. Therefore, it is important to know if prior infection with a genotype 3 swine HEV will confer protective immunity against subsequent exposure to genotypes 3 and 4 human and swine HEV. In this study, specific-pathogen-free pigs were divided into 4 groups of 6 each. Pigs in the three treatment groups were each inoculated with a genotype 3 swine HEV, and 12 weeks later, challenged with the same genotype 3 swine HEV, a genotype 3 human HEV, and a genotype 4 human HEV, respectively. The control group was inoculated and challenged with PBS buffer. Weekly sera from all pigs were tested for HEV RNA and IgG anti-HEV, and weekly fecal samples were also tested for HEV RNA. The pigs inoculated with swine HEV became infected as evidenced by fecal virus shedding and viremia, and the majority of pigs also developed IgG anti-HEV prior to challenge at 12 weeks post-inoculation. After challenge, viremia was not detected and only two pigs challenged with swine HEV had 1-week fecal virus shedding, suggesting that prior infection with a genotype 3 swine HEV prevented pigs from developing viremia and fecal virus shedding after challenges with homologous and heterologous genotypes 3 and 4 HEV. The results from this study have important implications for future development of an effective HEV vaccine.

Figure 1

IgG anti-HEV response in pigs inoculated with a genotype 3 swine HEV and subsequently challenged, at 12 weeks post-inoculation (wpi), with different strains of human and swine HEV. A: Pigs inoculated and challenged with PBS buffer. B: Pigs inoculated with a genotype 3 swine HEV and challenged at 12 wpi with a genotype 3 human HEV (US-2 strain). C: Pigs inoculated with a genotype 3 swine HEV and challenged at 12 wpi with the same genotype 3 swine HEV. D: Pigs inoculated with a genotype 3 swine HEV and challenged at 12 wpi with a genotype 4 human HEV (Taiwanese strain). Arrow in the X-axis indicates the time of challenge at 12 wpi. All pig were necropsied at 4 weeks post-challenge (wpc)