Safety of the hepatitis E vaccine for pregnant women: A preliminary analysis
Authors: Ting Wu, Feng-Cai Zhu, Shou-Jie Huang, Xue-Feng Zhang, Zhong-Ze Wang, Jun Zhang, Ning-Shao Xia
Journal: Hepatology (2011)

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 vaccine3 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 = 41 [22 vaccine, 19 placebo]), two (n = 23 [14 vaccine, 9 placebo]), or three (n = 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 ± 356.7 g versus 3,565.6 ± 531.6 g), lengths (50.7 ± 1.3 cm versus 50.8 ± 1.5 cm), and gestational ages (276.2 ± 7.6 days versus 276.6 ± 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. Ting Wu Ph.D.*, Feng-Cai Zhu M.Sc. , Shou-Jie Huang M.D.*, Xue-Feng Zhang M.Sc. , Zhong-Ze Wang M.D. , Jun Zhang M.D.*, Ning-Shao Xia M.D.*, * National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province, China, Dongtai Center for Disease Control and Prevention, Dongtai, Jiangsu Province, China.