Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: A large-scale, randomised, double-blind placebo-controlled, phase 3 trial

Jiangsu Provincial Centre for Disease Control and Prevention, Nanjing, Jiangsu Province, China.
The Lancet (Impact Factor: 45.22). 09/2010; 376(9744):895-902. DOI: 10.1016/S0140-6736(10)61030-6
Source: PubMed

ABSTRACT Seroprevalence data suggest that a third of the world's population has been infected with the hepatitis E virus. Our aim was to assess efficacy and safety of a recombinant hepatitis E vaccine, HEV 239 (Hecolin; Xiamen Innovax Biotech, Xiamen, China) in a randomised, double-blind, placebo-controlled, phase 3 trial.
Healthy adults aged 16-65 years in, Jiangsu Province, China were randomly assigned in a 1:1 ratio to receive three doses of HEV 239 (30 microg of purified recombinant hepatitis E antigen adsorbed to 0.8 mg aluminium hydroxide suspended in 0.5 mL buffered saline) or placebo (hepatitis B vaccine) given intramuscularly at 0, 1, and 6 months. Randomisation was done by computer-generated permuted blocks and stratified by age and sex. Participants were followed up for 19 months. The primary endpoint was prevention of hepatitis E during 12 months from the 31st day after the third dose. Analysis was based on participants who received all three doses per protocol. Study participants, care givers, and investigators were all masked to group and vaccine assignments. This trial is registered with, number NCT01014845.
11,165 of the trial participants were tested for hepatitis E virus IgG, of which 5285 (47%) were seropositive for hepatitis E virus. Participants were randomly assigned to vaccine (n=56,302) or placebo (n=56,302). 48,693 (86%) participants in the vaccine group and 48,663 participants (86%) in the placebo group received three vaccine doses and were included in the primary efficacy analysis. During the 12 months after 30 days from receipt of the third dose 15 per-protocol participants in the placebo group developed hepatitis E compared with none in the vaccine group. Vaccine efficacy after three doses was 100.0% (95% CI 72.1-100.0). Adverse effects attributable to the vaccine were few and mild. No vaccination-related serious adverse event was noted.
HEV 239 is well tolerated and effective in the prevention of hepatitis E in the general population in China, including both men and women age 16-65 years.
Chinese National High-tech R&D Programme (863 programme), Chinese National Key Technologies R&D Programme, Chinese National Science Fund for Distinguished Young Scholars, Fujian Provincial Department of Sciences and Technology, Xiamen Science and Technology Bureau, and Fujian Provincial Science Fund for Distinguished Young Scholars.

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Available from: James Wai-Kuo Shih, Sep 28, 2015
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    • "Several subunit vaccines have been commercially available for human use [1], including the VLP vaccines against hepatitis B virus (HBV) [2] [3], human papilloma virus (HPV) [4e7], and hepatitis E virus (HEV) [8] [9]. Furthermore, two other subunit vaccines have been developed for use in domestic pigs against porcine circovirus type 2 (PCV2) infection and diseases [10] [11]. "
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    Biomaterials 06/2014; 35(29). DOI:10.1016/j.biomaterials.2014.06.021 · 8.56 Impact Factor
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    • "Increased incidences of indigenous HE cases have been reported in developing and developed countries [29]. Although a recombinant vaccine preventing from HEV infection is available in China [30], the pathogenesis of HE remains unclear. "
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    PLoS ONE 06/2014; 9(6):e100787. DOI:10.1371/journal.pone.0100787 · 3.23 Impact Factor
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    • "In both cases, the macaques were protected against homologous and heterologous challenge by HEV strains (Krawczynski et al. 2011). The large-scale clinical trial of a capsid-based recombinant vaccine involving 11,165 individuals (Zhu et al. 2010) has led to the approval of the first commercial HEV vaccine in China (Proffitt 2012). Pigs have been used as a model for HEV vaccine trials and assessment of cross-protective potentials of recombinant HEV antigens, which is essential for the development of vaccines that protect against the zoonotic genotypes 3 and 4 strains of HEV. "
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    ABSTRACT: Hepatitis E virus (HEV) is a single-stranded, positive-sense RNA virus in the family Hepeviridae. Hepatitis E caused by HEV is a clinically important global disease. There are currently four well-characterized genotypes of HEV in mammalian species, although numerous novel strains of HEV likely belonging to either new genotypes or species have recently been identified from several other animal species. HEV genotypes 1 and 2 are limited to infection in humans, whereas genotypes 3 and 4 infect an expanding host range of animal species and are zoonotic to humans. Historical animal models include various species of nonhuman primates, which have been indispensable for the discovery of human HEV and for understanding its pathogenesis and course of infection. With the genetic identification and characterization of animal strains of HEV, a number of naturally occurring animal models such as swine, chicken, and rabbit have recently been developed for various aspects of HEV research, including vaccine trials, pathogenicity, cross-species infection, mechanism of virus replication, and molecular biology studies. Unfortunately, the current available animal models for HEV are still inadequate for certain aspects of HEV research. For instance, an animal model is still lacking to study the underlying mechanism of severe and fulminant hepatitis E during pregnancy. Also, an animal model that can mimic chronic HEV infection is critically needed to study the mechanism leading to chronicity in immunocompromised individuals. Genetic identification of additional novel animal strains of HEV may lead to the development of better naturally occurring animal models for HEV. This article reviews the current understanding of animal models of HEV infection in both natural and experimental infection settings and identifies key research needs and limitations.
    ILAR journal / National Research Council, Institute of Laboratory Animal Resources 06/2014; 55(1):187-99. DOI:10.1093/ilar/ilu007 · 2.39 Impact Factor
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