Hepatitis E is a liver infection caused by a virus that typically leads to inflammation. While many individuals experience a mild illness that resolves without specific treatment, it can progress to a severe condition in certain populations. A vaccine has been developed to prevent this disease, which poses a significant threat, especially in areas with compromised sanitation.
Understanding the Hepatitis E Virus
The Hepatitis E virus (HEV) primarily spreads through the fecal-oral route, often via water contaminated by infected individuals’ feces. In developed regions, sporadic cases are often linked to consuming raw or undercooked pork, venison, or shellfish. The virus can also be transmitted from animals to humans, particularly genotypes 3 and 4 of HEV.
Many people infected with HEV, especially young children, do not show any symptoms. Symptoms typically appear two to six weeks after exposure and can include fatigue, fever, nausea, stomach pain, or vomiting. Jaundice, characterized by yellowing of the skin or eyes, and dark urine are also common indicators of infection.
Certain groups face a higher risk of developing severe disease outcomes, including long-term liver problems or liver failure. Pregnant women are particularly susceptible, with reported mortality rates reaching up to 20% in some cases. Individuals with pre-existing liver conditions and compromised immune systems also belong to this high-risk category.
Development and Mechanism of the Vaccine
The Hepatitis E vaccine, known as HEV 239 and commercially as Hecolin, is a significant advancement in preventing this infection. This recombinant subunit vaccine utilizes a manufactured protein designed to mimic a specific part of the virus. Specifically, it contains a 239-amino acid protein that corresponds to amino acids 368-606 of the HEV genotype 1 capsid protein, produced in Escherichia coli bacteria.
This lab-made protein is formulated with alum as an adjuvant, a substance that helps enhance the body’s immune response. When administered, the vaccine introduces this mimicry protein to the immune system, prompting it to recognize the viral component without causing actual disease. This process allows the body to develop protective antibodies, preparing it to fight off a future HEV infection.
The vaccine is administered intramuscularly, typically into the deltoid muscle of the arm. The standard immunization schedule involves three separate doses given over a six-month period: an initial dose, a second dose one month later, and a third dose at six months. Each dose usually contains 30 micrograms of the HEV 239 antigen.
Efficacy and Safety Profile
Clinical trials have demonstrated a high level of protection from the Hepatitis E vaccine. A large-scale Phase III randomized trial conducted in China, involving over 112,000 healthy adults aged 16 to 65 years, reported 100% vaccine efficacy in preventing clinical Hepatitis E during the 12 months following the third dose. This study also indicated an overall protection rate of 95.5% over a 19-month follow-up period.
Long-term studies have further supported its effectiveness, showing an efficacy of 86.6% after 10 years for individuals who received the full three-dose regimen. The vaccine has also shown cross-protective efficacy, meaning it can protect against different genotypes of the virus, specifically genotypes 1 and 4. Even a two-dose schedule, given at 0 and 1 month, provided 100% efficacy for several months before the third dose, offering satisfying protection against subclinical infection.
Regarding safety, the HEV 239 vaccine has generally been well tolerated across various clinical studies. Common side effects are typically mild and localized to the injection site, including pain and bruising. While these local reactions may occur more frequently in vaccinated individuals compared to placebo recipients, there have been no statistically significant differences in systemic adverse events such as fever or headache. Large-scale studies have not identified any significant long-term safety concerns. However, some research suggests a potential elevated risk of miscarriage in women vaccinated during pregnancy or shortly before conception, although real-world data on vaccine safety in pregnant women remains limited.
Global Availability and Recommendations
The Hepatitis E vaccine, Hecolin, is currently licensed and available for use in two countries: China, where it received approval in 2011, and Pakistan, where it was approved in 2021. Despite its proven efficacy and safety in clinical trials, its global availability remains limited. The manufacturer has not yet sought pre-qualification from the World Health Organization (WHO), which is an internationally recognized standard for vaccine quality, safety, and efficacy.
The World Health Organization acknowledges the vaccine’s effectiveness and safety profile. However, it has not issued a universal recommendation for routine inclusion of the Hepatitis E vaccine in national immunization programs for all populations or travelers. This position is partly due to existing data gaps concerning the global incidence of HEV infection and disease burden in various regions. Instead, the WHO suggests that national health authorities consider and decide on the vaccine’s deployment based on their local epidemiological context. This approach means the vaccine is typically considered for use in specific, high-risk scenarios, such as during outbreaks of Hepatitis E or for high-risk groups residing in endemic areas. For instance, the vaccine was utilized in a mass vaccination campaign in the Bentiu internally displaced persons camp in South Sudan in 2022, marking its first use in an outbreak setting outside of China.