Hepatitis E Vaccine Effective and Long Lasting

Jennifer Garcia

March 05, 2015

A new, long-term study of a hepatitis E vaccine finds that it is 86.8% effective and that immunity may last for at least 4.5 years.

Jun Zhang, MSc, from the State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biologic Products, School of Public Health, Xiamen University, China, and colleagues published their findings in the March 5 issue of the New England Journal of Medicine.

As part of a 2007 blinded, placebo-controlled, phase 3 trial, the researchers randomly assigned 112,604 healthy adults in Dongtai, in the Jiangsu province of China, to receive either three doses of a hepatitis E vaccine (vaccine group, 56,302) or hepatitis B vaccine (control group, 56,302). In an extended follow-up, reported in the current article, the researchers followed patients for 19 months, for a total of 54 months (4.5 years). Unblinding occurred only after safety and efficacy data were obtained for the long follow-up period.

Patients were followed through a hepatitis surveillance program that included 205 village and private clinics, as well as township and city hospitals throughout Dongtai. Hepatitis was confirmed before unblinding and was based on "the presence of at least two of the following three markers: a positive test for IgM antibodies against [hepatitis E virus], a positive test for [hepatitis E virus] RNA, and a level of [immunoglobulin G] antibodies against [hepatitis E virus] that was at least four times as high as a level measured previously at any time during the same illness."

During the 54-month study period, there were seven cases of hepatitis in the vaccine group (0.3 cases per 10,000 person-years) and 53 cases in the control group (2.1 cases per 10,000 person-years). The researchers determined a vaccine efficacy of 86.8% (95% confidence interval, 71.0% - 94.0%) in the modified intent-to-treat analysis. None of the adverse effects reported were considered related to the vaccine, and no clinical difference between the groups in terms of disease manifestation was noted.

In addition to efficacy, the study authors evaluated immunogenicity of the vaccine and found that 52% of the 5567 participants tested were seronegative at baseline, of whom 99.9% seroconverted after vaccination with the HEV vaccine. Seroconversion rates were similar among participants who received one, two, or three doses of the HEV vaccine and who were seronegative at baseline. Among those who had received three doses of the vaccine, 87% were still seropositive at the end of month 54. Antibody levels were slightly lower among participants who received two doses of the vaccine; however, whether a two-dose vaccine schedule should be recommended "needs to be proven in specifically designed efficacy trials," the study authors note.

The authors acknowledge limitations to the study such as fluctuations in the sensitivity for disease surveillance, as well as the fact that, as most cases of hepatitis were genotype 4, efficacy of the vaccine against other hepatitis E genotypes is unknown.

Kenneth E. Sherman, MD, PhD, director of the Division of Digestive Diseases at the University of Cincinnati College of Medicine in Ohio, told Medscape Medical News, "The genotype of HEV virus present in China, where the study was performed, is not the dominant type present in Europe and the US. In those places, genotype 3 is predominant. Whether this vaccine would be effective against other genotypes remains unknown." Dr. Sherman was not involved with the study.

Dr. Sherman also noted that this vaccine has not yet been approved by the US Food and Drug Administration; however, "[t]he availability of an efficacious and durable vaccine for HEV is an important step in preventing HEV disease in endemic areas of the world and perhaps to travelers to those areas."

Funding for this study was provided by the Chinese Ministry of Science and Technology and a grant from the Xiamen Innovax Biotech Company. Various authors disclosed personal fees received from Xiamen Innovax Biotech Company. Dr. Sherman has disclosed no relevant financial relationships.

N Eng J Med. 2015;372:914-922. Abstract

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