No abstract

Immunization with this hepatitis E vaccine induced antibodies against HEV and provided protection against hepatitis E for up to 4.5 years. (Funded by the Chinese Ministry of Science and Technology and others; ClinicalTrials.gov number, NCT01014845.).

Laboratory diagnosis of acute infection of hepatitis E virus (HEV) is commonly based on the detection of HEV RNA, IgM and/or rising IgG levels. However, the profile of these markers when the patients present have not been well determined. To clarify the extent of misdiagnosed sporadic hepatitis E in the initial laboratory detection, serial sera of 271 sporadic acute hepatitis cases were collected, detected and the dynamics of each acute marker during the illness course were analyzed. 91 confirmed cases of hepatitis E were identified based on the presentation of HEV RNA, IgM or at least 4 fold rising of IgG levels. 21 (23.1%) hepatitis E cases were false negative for the viral RNA and 40 (44.0%) for rising IgG, because occurrence of these markers were confined to acute phase of infection and viremia had already subsided and antibody level peaked when these patients presented. IgM was detected in 82 (90.1%) cases. It is the most prevalent of the three markers, because the antibody persisted until early convalescence. Nine cases negative for IgM were positive for rising IgG and one was also positive for the viral RNA; all of these nine cases showed high avid IgG in their acute phase sera, which indicated re-infection. In summary, it is not practicable to determine the true occurrence of sporadic hepatitis E. Nevertheless, it could be closely approximated by approach using a combination of all three acute markers.

A truncated structural protein of hepatitis E virus (HEV), p239, occurs as 23 nm particles consisting of partial homodimers. As the latter resemble the HEV capsomere structurally and antigenically, it was postulated that the recombinant protein may serve as a probe for the HEV receptor. This hypothesis was supported by findings that purified p239 bound and penetrated different cell lines that are susceptible to HEV, and inhibited HEV infection of these cells. The binding was blocked by four of six monoclonal antibodies (mAbs) reactive against the dimeric domain of p239, and by two of three mAbs reactive against its monomeric domain, suggesting that binding may involve a portion of each domain. Mutation affecting the monomeric domain had no effect on binding or capacity to block HEV infection, whereas that affecting the dimeric domain diminished binding of the mutant peptide markedly and abrogated its capacity to block HEV infection. These results suggest that HEV infection might involve distinct receptor-binding sites.

Immunity acquired from infection or vaccination protects humans from symptomatic hepatitis E. However, whether the risk of hepatitis E virus (HEV) infection is reduced by the immunity remains unknown. To understand this issue, a cohort with 12 409 participants randomized to receive the hepatitis E vaccine Hecolin(®) or placebo were serologically followed up for 2 years after vaccination. About half (47%) of participants were initially seropositive. A total of 139 infection episodes, evidenced by four-fold or greater rise of anti-HEV level or positive seroconversion, occurred in participants who received three doses of treatment. Risk of infection was highest among the baseline seronegative placebo group participants (2.04%). Pre-existing immunity and vaccine-induced immunity lower the risk significantly, to 0.52% and 0.30%, respectively. In conclusion, both vaccine-induced and naturally acquired immunity can effectively protect against HEV infection.

Hepatitis E virus (HEV) infection is one of the main causes of acute hepatitis worldwide. A recombinant hepatitis E vaccine, HEV 239, has been licensed in China for immunizing adults of 16 y old and above. The vaccine antigen contains pORF2 aa 368 -606 of the HEV genotype 1 expressed in E. coli. The quality of the vaccine is controlled through a combination of biophysical, biochemical and immunochemical methods. The vaccine is well tolerated in adults. The efficacy of the HEV 239 vaccine against symptomatic and asymptomatic infection had been proven to be high during a Phase III clinical trial and long-term follow up. The safety and efficacy of HEV 239 vaccine in certain high-risk populations remains to be further investigated.

No abstract

High morbidity and mortality among pregnant women are characteristic identifiers of waterborne epidemic outbreaks of hepatitis E. 1,2 In the absence of effective treatment, vaccination offers a potential means to reduce the morbidity and mortality associated with pregnancy. 3 However, clinical studies are hampered by safety concerns, because vaccination during pregnancy is generally contraindicated.A review of the records of a recent phase 3 clinical trial of the recombinant hepatitis E vaccine 3 identified 37 of 31,791 women in the vaccine group and 31 of 31,735 women in the placebo group who were pregnant at the time of enrollment or became pregnant during the course of the study and were inadvertently given one (n ¼ 41 [22 vaccine, 19 placebo]), two (n ¼ 23 [14 vaccine, 9 placebo]), or three (n ¼ 4 [1 vaccine, 3 placebo]) doses of the HEV 239 vaccine or the control HBV vaccine. A total of 53 doses were received by the 37 pregnant women in the vaccine group, and 46 doses were received by the 31 pregnant women in the placebo group. Table 1 compares the adverse reactions observed in each of these subjects with that of two matched nonpregnant women. Only one subject in the vaccine group reported grade 1 pain at the site of inoculation. No serious adverse events were reported. The rates of adverse reactions to either vaccine were similar to those observed for the matched nonpregnant women. Nineteen (51.3%) of the women in the vaccine group and 14 (45.2%) in the placebo group underwent elective abortion. All the other women went on to give normal full-term birth by vaginal delivery (seven in the vaccine group versus seven in the placebo group) or by cesarean section (11 in the vaccine group versus 10 in the placebo group). No spontaneous abortion occurred, and the babies were born without congenital anomalies. The weights (3,573.5 6 356.7 g versus 3,565.6 6 531.6 g), lengths (50.7 6 1.3 cm versus 50.8 6 1.5 cm), and gestational ages (276.2 6 7.6 days versus 276.6 6 7.1 days) of the babies born to the mothers in the vaccine group and the placebo group, respectively, were comparable (P > 0.05).Blood samples from both month 0 and month 7 were available for one woman who received the third dose of HEV 239 vaccine during month 4 of her pregnancy. Her antibody level increased from undetectable to 34.7 Wu/mL, which is higher than that of 80% of subjects who received three doses of HEV 239 vaccine. None of the 68 pregnant women acquired hepatitis E.These preliminary observations suggest that the HEV 239 vaccine is safe for both mother and fetus and partially allay concerns regarding the safety of further clinical trials to substantiate this finding.