Comparison of the safety and immunogenicity of live attenuated and inactivated hepatitis A vaccine in healthy Chinese children aged 18 months to 16 years: results from a randomized, parallel controlled, phase IV study

Abstract

For large-scale immunization of children with hepatitis A (HA) vaccines in China, accurately designed studies comparing the safety and immunogenicity of the live attenuated HA vaccine (HA-L) and inactivated HA vaccine (HA-I) are necessary. A randomized, parallel controlled, phase IV clinical trial was conducted with 6000 healthy children aged 18 months to 16 years. HA-L or HA-I was administered at a ratio of 1: 1 to randomized selected participants. The safety and immunogenicity were evaluated. Both HA-L and HA-I were well tolerated by all participants. The immunogenicity results showed that the seroconversion rates (HA-L versus HA-I: 98.0% versus 100%, respectively, p >0.05), and geometric mean concentrations in participants negative for antibodies against HA virus IgG (anti-HAV IgG) before vaccination did not differ significantly between the two types of vaccines (HA-L versus HA-I first dose: 898.9 versus 886.2 mIU/mL, respectively, p >0.05). After administration of the booster dose of HA-I, the geometric mean concentrations of anti-HAV IgG (HA-I booster dose: 2591.2 mIU/mL) was higher than that after the first dose (p <0.05) and that reported in participants administered HA-L (p <0.05). Additionally, 12 (25%) of the 48 randomized selected participants who received HA-L tested positive for HA antigen in stool samples. Hence, both HA-L and HA-I could provide acceptable immunogenicity in children. The effects of long-term immunogenicity after natural exposure to wild-type HA virus and the possibility of mutational shifts of the live vaccine virus in the field need to be studied in more detail.

Long-term immunogenicity and immune persistence of live attenuated and inactivated hepatitis a vaccines: a report on additional observations from a phase IV study

“…Inactivated and live attenuated HA vaccines account for half of the market share of the Chinese national immunization programme. HA-L involves only a single dose; therefore, it is less expensive and easier to implement than the classical two-dose HA-I vaccine, but the disadvantage is that the virus in the live attenuated vaccine can possibly replicate and be actively excreted [15]. Both HA vaccines used in this trial included freeze-dried HA-L and HA-I preparations that had shown good safety and immunogenicity profiles during phase I, II and III clinical trials.…”

“…This was a randomized, double-blind, parallel controlled phase IV clinical trial conducted in counties in Jiangsu Province, China, where an HA epidemic had not occurred for nearly 3 years. The trial methods and sample size calculation have been previously reported [15]. This trial recruited three groups of participants: 18e36 months of age (infant group), 3e16 years old (children group) and 16 years old or more (adult group).…”

“…Although many clinical trials have examined the immunogenicity and persistence of HAVs, few studies have been conducted comparing HA-I and HA-L in a single trial, quantitatively measuring the serum HA antibody (HAAb) titres and seroconversion rates during the 3 years after vaccination [11e14]. We previously reported on the safety and immunogenicity of HA-I and HA-L 28 days after the full vaccination course in 6000 healthy Chinese children aged 18 months to 16 years [15]. In this study, we report the continued results of a Phase IV clinical trial conducted in 9000 healthy individuals over 18 months of age (including participants over 16 years of age) during a period of 3 years following vaccination.…”

Hepatitis A vaccination

“…81 In a randomized, parallel controlled, phase IV study in China, 12 (25%) of the 48 randomized selected participants who received HepA-L tested positive for HA antigen in stool samples within 28 d after vaccination, and the detection rates of vaccine HAAg in stool samples on d 1, 7, 14, 21 and 28 postvaccination were not significantly different. 43 In another Chinese study, HAV was isolated from 70% (53/75) of tool samples from children whose roommates received HepA-L, but elevated ALT was not detected among these children, suggesting that HepA-L could cause horizon transmission of HAV, but could not induce hepatitis A clinical disease. 82 Further surveillance should be implemented on the possibility of horizon transmission of HepA-L and its implication in hepatitis A elimination in countries using HepA-L.…”

“…[33][34][35][36][37] Seroconversion of anti-HAV could be achieved after two doses of HepA-I among almost all children regardless of the manufacture of the vaccine. 5,22,28,29,[37][38][39][40][41][42][43] The anti-HAV seroconversion rate could reach approximately 95% at 14-30 d after the first dose of HepA-I, 22,29,41,44,45 and the second-dose could greatly elevate the anti-HAV level postvaccination. 22,37,43 A similar seroconversion rate after one-dose vaccination was reported between HepA-I and HepA-L among children and adults, 39,42,43 and GMC was much higher after two doses of HepA-I compared with onedose of HepA-I or HepA-L. 42 The nature of the prompt immune response after HepA vaccination is important for its use for PEP.…”