Hepatitis E virus (HEV) is widespread and continues to cause large outbreaks in developing countries. One recombinant vaccine was shown to be safe and immunogenic in men in Nepal, where only one of the four HEV genotypes had been isolated (JW Infect Dis Feb 28 2007). Could a vaccine derived from HEV genotype 1 protect against other genotypes in a general adult population? To find out, investigators (2 of whom were employees of the vaccine maker) conducted a double-blind, phase III trial of another candidate vaccine in a region of China where genotypes 1 and 4 circulate.

A total of 112,604 healthy adults (56% women) aged 16 to 65 were randomized to receive three doses of recombinant hepatitis E antigen (vaccine group) or hepatitis B vaccine (placebo group), administered at 0, 1, and 6 months. Cases of suspected hepatitis E were identified through enhanced surveillance and confirmed by presence of acute illness lasting 3 days, elevated serum alanine aminotransferase concentrations (2.5 times the upper limit of normal), and positive test results (HEV IgM and RNA, 4-fold increase in HEV IgG, or both).

Overall, 23 cases of hepatitis E developed during 19-month follow-up (1 in a vaccine-group participant who received 1 dose; 22 in placebo-group participants). Among the 97,356 individuals who received three doses, 15 (all in the placebo group) had confirmed hepatitis E during 12-month follow-up (vaccine efficacy, 100%).

In the 2645 participants with active surveillance for reactogenicity, local adverse events were more common in the vaccine group than in the placebo group (13.5% vs. 7.1%; P<0.0001). Serious adverse events occurred at similar rates in the two groups and were deemed unrelated to vaccination. Among the 11,165 participants studied for immunogenicity, 47.3% were HEV seropositive before vaccination. After three doses, 4-fold increases in antibody concentration were seen in 98.7% of vaccine-group participants vs. 2.1% of placebo-group participants (all with subclinical infection).

Comment: In this trial among adults, almost half of whom had antibody to HEV before vaccination, this recombinant vaccine was safe and highly efficacious. Future studies will need to assess duration of protection, efficacy in regions where other HEV genotypes circulate, and efficacy in groups at highest risk for severe morbidity (e.g., infants, pregnant women, individuals with chronic diseases). An editorialist speculates that the vaccine might be useful in outbreak situations.

— Mary E. Wilson, MD

Published in Journal Watch Infectious Diseases September 1, 2010