Long-term immunogenicity after single and booster dose of a live attenuated hepatitis A vaccine: Results from 8-year follow-up

Abstract

Live, attenuated hepatitis A vaccines are used widely in China but there is uncertainty regarding the persistence of vaccine-induced anti-HAV antibodies after single dose and booster dose administrated at month 12. A large scale clinical trial to evaluate the live, attenuated hepatitis A vaccine was conducted in Hebei province between 1996 and 1999. Five years after the trials, children in single dose and booster dose groups were bled and followed. Seventy two percent (61/85) of children who received a single trial dose had detectable anti-HAV antibodies for 96 months (GMC at 96 months: 89.0 mIU/mL). In the booster group 98% (48/49) children remained anti-HAV positive with GMC of 262.8 mIU/mL at month 96. The reinjection with live attenuated HAV vaccine can elicit a booster effect. Results from single dose group seems not to support the need for booster doses of live attenuated hepatitis A vaccine in immunocompetent individuals regarding the persisting anti-HAV and anamnestic response of a single dose vaccine. Continued monitoring of anti-HAV antibodies is needed for a rational hepatitis A immunization strategy in China.

Introduction

With the improvements in socioeconomic status, clean water, sanitation and immunization of effective vaccine, a remarkable decline of hepatitis A was noted in China over the past decade. Countrywide, the reported number of hepatitis A virus (HAV) cases dropped from 326,696 in 1994 to 95,408 in 2004 [1], [2]. The HAV seroprevalence dropped correspondingly [3], [4]. These data suggest that China is becoming an intermediate to low HAV endemic country. In 1992 live attenuated hepatitis A vaccines based on the H2 and LA-1 strains were developed in China [5], [6]. Between 1996 and 1999, we conducted large scale, controlled clinical trials to assess the safety and protective efficacy of the H2 strain hepatitis A vaccine in Shanghai and Zhengding, Hebei province. The trials demonstrated good tolerance, high immunogenicity. The overall protective efficacy of the vaccine was 95% (95% CI 74–99%) [7], [8], [9], [10].

Presently in China, the live, attenuated hepatitis A vaccine is recommended for children living in relatively low prevalence regions and high risk population. Estimates of the duration of protection provided by single and booster doses will allow recommending a rational immunization policy. However, up to now no studies have explored the persistence of live attenuated vaccine-induced anti-HAV antibodies. We therefore undertook a follow-up study to assess the persistence of anti-HAV antibodies in vaccinees 5 years after the clinical trials.