Development, Production, and Postmarketing Surveillance of Hepatitis A Vaccines in China

Fuqiang Cui,Yvan J Hutin,Weizhong Yang,Hui Zheng,Xiaofeng Liang,Fuzhen Wang

doi:10.2188/jea.je20130022

Abstract

China has long experience using live attenuated and inactivated vaccines against hepatitis A virus (HAV) infection. We summarize this experience and provide recent data on adverse events after immunization (AEFIs) with hepatitis A vaccines in China. We reviewed the published literature (in Chinese and English) and the published Chinese regulatory documents on hepatitis A vaccine development, production, and postmarketing surveillance of AEFI. We described the safety, immunogenicity, and efficacy of hepatitis A vaccines and horizontal transmission of live HAV vaccine in China. In clinical trials, live HAV vaccine was associated with fever (0.4%–5% of vaccinees), rash (0%–1.1%), and elevated alanine aminotransferase (0.015%). Inactivated HAV vaccine was associated with fever (1%–8%), but no serious AEFIs were reported. Live HAV vaccine had seroconversion rates of 83% to 91%, while inactivated HAV vaccine had seroconversion rates of 95% to 100%. Community trials showed efficacy rates of 90% to 95% for live HAV and 95% to 100% for inactivated HAV vaccine. Postmarketing surveillance showed that HAV vaccination resulted in an AEFI incidence rate of 34 per million vaccinees, which accounted for 0.7% of adverse events reported to the China AEFI monitoring system. There was no difference in AEFI rates between live and inactivated HAV vaccines. Live and inactivated HAV vaccines manufactured in China were immunogenic, effective, and safe. Live HAV vaccine had substantial horizontal transmission due to vaccine virus shedding; thus, further monitoring of the safety of virus shedding is warranted.

Highlights

In 1992, safe and effective vaccines for prevention of hepatitis A were licensed in a number of countries.[1]
We reviewed official licensure documents and policy decisions regarding the use of hepatitis A vaccine in China
Production and quality assurance: The freeze-dried, live attenuated hepatitis A vaccine is made with the H2 strain and KMB17 cell substrate and includes a protective additive that is patented in China

Summary

INTRODUCTION

In 1992, safe and effective vaccines for prevention of hepatitis A were licensed in a number of countries.[1]. In 1988, the largest hepatitis A outbreak in the world (more than 310 000 cases) occurred in Shanghai, China. It heightened public concern[3] and illustrated how accumulation of susceptible individuals after a decrease in transmission could result in large outbreaks of disease in the absence of vaccination-induced population immunity. In 2007, hepatitis A vaccine was fully integrated into the Chinese national immunization program and is provided free to all children older than 18 months. The Chinese national immunization program uses both the live attenuated vaccine (1 dose, subcutaneous route, about half of the market share) and the inactivated vaccine (2 doses, 6 months apart, about half of the market share). The Chinese experience in developing and using the hepatitis A vaccine has not been widely shared, since most studies have been published in Chinese

LITERATURE REVIEW AND SURVEILLANCE

H2 LA-1

Findings

H2 H2 LA-1 LA-1 H2