New Vaccine Prevents Hepatitis E Virus Infection in Healthy Adults in China

Fran Lowry

August 23, 2010

August 23, 2010 — A recombinant bacterial hepatitis E virus (HEV) vaccine has been found to be safe and effective in preventing HEV infection in healthy adults in the general population in China, according to a new study published online today in The Lancet.

"[HEV] is a major cause of sporadic and epidemic hepatitis. Seroprevalence data suggest that a third of the world's population has been infected with the virus," write Feng-Cai Zhu, MSc, from Jiangsu Provincial Centre for Disease Control and Prevention, Nanjing, China, and colleagues. "Although most cases are in developing countries, [HEV] is no longer rare and it might be the most common type of acute viral hepatitis in industrialized countries."

According to the article, HEV is clinically indistinguishable from other types of acute viral hepatitis but tends to be self-limited and does not usually become chronic. Infection with HEV is more severe, with a mortality rate ranging from 5% to 25%, in the elderly and in pregnant women. Pregnant women who survive HEV infection also have high rates of spontaneous abortion and stillbirth. Patients with chronic liver disease who become infected with HEV have poor outcomes, and every year, 13,000 to 26,000 HEV-related deaths occur in industrialized countries.

The aim of the current study was to assess the efficacy and safety of the recombinant HEV vaccine, HEV 239 (Hecolin; Xiamen Innovax Biotech), in a randomized, double-blind, placebo-controlled phase 3 trial.

The study included healthy adults aged 16 to 65 years who were randomly assigned to receive 3 doses of HEV 239 or placebo in the form of hepatitis B vaccine intramuscularly at 0, 1, and 6 months. The participants were followed up for 19 months; the primary endpoint was prevention of HEV during 12 months from day 31 after the third dose.

Of the 122,179 people from 11 townships who attended the enrolment visit between August and October, 2007, 112,604 participants fulfilled eligibility requirements, were randomly assigned to the study group, and received at least 1 dose of vaccine or placebo. A total of 97,356 participants received 3 doses of either HEV 239 (48,693 participants) or placebo (48,663 participants ) vaccines and were included in the primary analysis.

The study found that 15 participants in the placebo group developed HEV compared with none in the HEV 239 vaccine group, for a vaccine efficacy rate of 100% after 3 doses (95% confidence interval, 72.1% - 100.0%).

The vaccine was safe and well tolerated. Most adverse events were mild and occurred with similar frequency in the vaccine and placebo groups. There were no serious adverse events from the HEV 239 vaccine, the authors report.

Exclusion of individuals with chronic liver disease was a limitation of the study. Because data suggest that this group should be prioritized for vaccination, additional studies should be done to assess the benefit of HEV 239 in these individuals. Another limitation was the lack of a HEV case in the vaccine group, which meant that the protective antibody concentration could not be assessed.

The authors conclude that further studies are needed to assess the safety and to support the benefits of HEV 239 in pregnant women, children aged 15 years and younger, and adults older than 65 years.

The report of a successful phase 3 study of the HEV vaccine is an important event in the prevention and control of HEV, Scott D. Holmberg, MD, from the US Centers for Disease Control and Prevention, Atlanta, Georgia, wrote in an accompanying editorial.

He agrees that the efficacy and safety of the vaccine need to be tested in pregnant women, children, and the elderly, and points out that the duration of protection afforded by HEV 239 is not yet known.

"Still, the recorded 100% vaccine efficacy in recipients of 2 vaccinations a month apart suggests that HEV vaccine can be an important component in outbreak control," Dr. Holmberg writes. "In highly endemic regions, a safe and effective vaccine (if affordable) raises the prospect of routine HEV vaccination to reduce both sporadic and epidemic HEV."

Finally, Dr. Holmberg comments that vaccines should never substitute or cause to delay improvements in overall sanitation. "However," he adds, "in view of the slow rate of improvement of sanitary conditions in many areas of Asia and Africa, this vaccine might be our best new stopgap in the effort to control the scourge of HEV in many parts of the world."

The study was supported by the Chinese National High-Tech Research & Development Programme, Chinese National Key Technologies Research & Development 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. Two of the study authors report that they are employees of Xiamen Innovax. The other study authors and Dr. Holmberg have disclosed no relevant financial relationships.

Lancet. Published online August 23, 2010.