Hepatitis E Vaccine: Current Status and Future Prospects

Samad Amini-Bavil-Olyaee; Christian Trautwein; Frank Tacke

Disclosures

Future Virology. 2009;4(2):143-154. 

In This Article

Abstract and Introduction

Abstract

HEV, a positive ssRNA and nonenveloped virus, is endemic in many developing countries and one of the most frequent causes of acute hepatitis after fecal-oral transmission. Pregnant women are at particular risk for a fatal course of disease, including maternal and fetal mortality. Recent reports indicate that HEV genotype 3, possibly related to zoonotic transmission, may cause chronic hepatitis in some immunosuppressed organ transplant patients. Various approaches have been conducted to develop HEV vaccines, but only one candidate, a recombinant HEV (rHEV) vaccine generated from Spodoptera frugiperda-9 cells by baculoviruses expressing the HEV capsid antigen, has reached clinical Phase I and II trials so far. These trials suggest that the rHEV vaccine is safe and can prevent clinically overt acute hepatitis E in high-risk populations. We herein review the different approaches in HEV-vaccine development and critically discuss the current status and future directions of the rHEV vaccine used in clinical trials.

Introduction

Viral hepatitis is a major public health problem in the world, and it can be caused by blood- and food-borne viruses. Blood-borne hepatitis agents are HBV, HCV and HDV, whereas HAV and HEV are food-borne hepatitis viruses. HEV infection is an important infectious agent in developing countries (endemic areas), but it is also an emerging disease in developed countries (sporadic areas), which is likely due to travel or immigration from endemic areas.[1,2,3,4,5] The main route of human HEV transmission is fecal-oral (fecally contaminated water),[6,7,8] although other routes were also reported such as person-to-person transmission,[9,10] blood products,[11,12] mother-to-child transmission[13] and zoonotic transmission (e.g., by pigs, particularly in developed countries,[14,15] and seafood[16]). Epidemiologically, only one serotype of HEV exists in the world, and the main HEV endemic areas are displayed in Figure 1. Genetically, the virus has been classified into four genotypes and several subgenotypes designated 1 (1a-e), 2 (2a and b), 3 (3a-j) and 4 (4a-g).[17] Each genotype shows a distinct geographical distribution. Genotype 1 of HEV is reported from developing countries in Asia and Africa; genotype 2 has been detected in some countries in Africa as well as in Mexico; genotype 3 is distributed globally and genotype 4 of HEV is only found in Asian countries.[17,18] The genotypes may not only vary with respect to their geographical distribution, but also in their pathogenicity. Genotypes 1 and 2 are primarily human pathogens, causing acute hepatitis in young, nonimmunocompromised people; genotypes 3 and 4, however, have been found in swine and other animals and could therefore be responsible for zoonotic transmissions, preferentially in the elderly or in immunocompromised patients.[6]

Figure 1.

Geographical distribution of HEV.

HEV endemic areas in the world are shown by dark gray colour. Sporadic HEV infections can occur worldwide and have been reported in the USA, western Europe, South America and Australia.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....