Recombinant Hepatitis E Vaccine Is Effective in Preventing Infection

Although hepatitis E virus (HEV) infection is uncommon in the U.S., it is a major cause of acute hepatitis in developing countries. As much as one third of the entire world population probably has been infected with HEV. The overall case fatality rate for acute disease is 1% to 3%, but, in pregnant women, acute severe hepatitis is common, and the case fatality rate is 5% to 25%. The aim of this partially industry-sponsored, randomized, double-blind, phase II trial was to determine the efficacy of a recombinant-protein HEV (rHEV) vaccine.

A total of 5323 healthy adult men and nonpregnant women were recruited from 61 Nepalese Army units; however, only 2000 patients with absent or low anti-rHEV immunoglobulin levels (<20 Walter Reed antibody units/mL) were enrolled. Subjects were given doses of vaccine or placebo intramuscularly at 0, 1, and 6 months; 84% of subjects received all three doses. The primary study endpoint was prevention of definite HEV infection occurring at least 14 days after the third dose of vaccine. Acute HEV infection (signs, symptoms, and laboratory testing consistent with acute hepatitis) was identified by active surveillance. The presence of PCR-identified HEV RNA and appropriate titers of anti-rHEV immunoglobulins were required to diagnose hepatitis.

Acute HEV infection developed in 69 participants: 3 in the vaccine group (0.3%) and 66 in the placebo group (7.4%). The efficacy of a three-dose vaccine course was 95.5% (95% CI, 85.6%–98.6%). The efficacy of a two-dose vaccine course was 85.7%. Injection-site pain was more common in the vaccine group (P=0.03); other adverse events occurred at similar rates in the groups.