Hepatitis E vaccine shows long-term effectiveness

Last Updated: 2015-03-04

By Gene Emery

NEW YORK (Reuters Health) - An updated analysis of a vaccine against potentially-deadly hepatitis E shows that it can provide long-term protection, at least for adults and children age 16 and older.

The new study, conducted in China and released March 4 online in The New England Journal of Medicine, found that antibody levels were sustained for at least 4.5 years, with no indication of serious adverse effects and no evidence that effectiveness was waning.

Hepatitis E virus, or HEV, is spread by human waste. It is particularly deadly to pregnant women, 5% to 25% of whom die from infection if it occurs in the third trimester. Those who survive face a higher risk of miscarriage.

Over all, the fatality rate is 1% to 3%.

"The big public health breakthrough here is that hepatitis E is a vaccine-preventable disease and we have a vaccine that can provide extended protection against this infection," said Dr. John Ward, director of the division of viral hepatitis at the Centers for Disease Control and Prevention in Atlanta.

"It can be a very powerful intervention in the parts of the world where this is the leading cause of hepatitis and where it causes mortality, particularly for pregnant women and other high-risk populations," he told Reuters Health by phone. "You get these explosive outbreaks that are very difficult to control in refugee camps. The disease causes a lot of suffering, misery and mortality."

It could become a recommended vaccination for some overseas travelers as well, he said.

In the new study, all of the volunteers in the hepatitis E group were scheduled to receive three doses of the Hecolin vaccine, made by Xiamen Innovax Biotech. Members of the control group received a hepatitis B vaccine instead.

Ultimately, there were seven confirmed cases of hepatitis E among the 55,240 patients who received the vaccine and 53 cases among the 55,185 in the control group (P<0.001), for an efficacy of 86.8%.

Among the seven cases in the group that received the vaccine, only three people had received all three doses. One of the seven had missed one dose and three had missed two of the three doses. Lab tests also showed higher antibody levels over time among those who received all three doses.

"The illness in these participants was moderate or mild; no deaths or episodes of liver failure were recorded," said the research team, led by Jun Zhang of the Xiamen University School of Public Health in Xiamen, China.

"The immune responses to the vaccine in participants with breakthrough infections are unknown, which makes it impossible to determine the level of antibody protection," they said.

"One of the major threats of HEV infection, especially in resource-limited areas, is that it can lead to large outbreaks, with tens of thousands of patients, and maternal and infant mortality," Zhang told Reuters Health in an email. "Fortunately, no such outbreak happened in the area we conduct the trial. However, it cannot be predicted when one will happen."

How long is protection likely to last?

"To date, all the evidence indicates sustained immunity in individuals who received all three shots of the vaccine for at least 4.5 years," said Zhang. "At the end of 4.5 years follow-up, more than 90% of the participants retained their antibodies against HEV, in spite of the lowered titer."

"The experience from other vaccines like hepatitis B vaccine teach us that even if the antibodies are undetectable after several years, the majority of the vaccinees will maintain their immune memory, which will help them to escape the severe damage of infection," Zhang said.

No serious adverse events were judged to be related to the vaccine, the researchers said.

But most of the people in China are infected with genotype 4 of HEV, and it's not clear that the vaccine will be as effective in regions where other genotypes prevail.

In China, the three shots cost about $100.

"Now that we have a vaccine, we need to see how best to apply it in these high-endemic settings," said Dr. Ward, coauthor of a Journal commentary on the research.

"Some special populations with higher risk of severe damage from HEV infection, such as women of childbearing age, elderly people and patients with chronic liver damage, will benefit more from a routine vaccination plan," Zhang said. "Besides them, blood donors (who risk transmitting HEV to recipients by transfusion), workers in the catering trade, caregivers of pregnant women or elderly people, could be candidates for vaccination to interrupt chains of transmission."

GlaxoSmithKline tested a recombinant vaccine against the disease but decided not to market it.

SOURCE: http://bit.ly/1BPVCJu

N Engl J Med 2015.