A rapid immune response to 2009 influenza A(H1N1) vaccines in adults: a randomized, double-blind, controlled trial.

A double-blind, randomized, controlled trial involving 706 adults was conducted to evaluate the immunogenicity and safety of different dosages of whole-virion or split-virion H1N1 influenza vaccines with or without aluminum adjuvant. A rapid and strong immune response was induced at day 14 after the first injection. The seroprotection rates ranged from 72.7% (95% confidence interval [CI], 62.7%-81.1%) for 5-microg whole-virion aluminum formulation to 97.0% (95% CI, 90.9%-99.7%) for 30-microg split-virion nonaluminum formulation. All formulations were well tolerated. The incidences of mild, moderate, and severe reactions were 71 (10.1%), 15 (2.1%), and 1 (0.1%) of 706 reactions, respectively. The 15-microg split-virion formulation had the best immunogenicity and safety.

[Safety and immunogenicity of combined hepatitis A and hepatitis B vaccine according to 0 and 6 months schedule in healthy children].

OBJECTIVE: To evaluate the safety and immunogenicity of the Bilive(TM) combined hepatitis A and hepatitis B vaccine in healthy children. METHODS: A total of 116 healthy children aged 1 - 10 years, who, without history of hepatitis A vaccine vaccination and anti-HAV negative, had completed the full immunization of hepatitis B vaccine were recruited in city of Changzhou in Jiangsu province. The Bilive(TM) combined hepatitis A and hepatitis B vaccine was administered according to a two-dose schedule (0, 6 months). The dosage was 250 U for hepatitis A antigen and 5 microg for hepatitis B surface antigen. The potential adverse effects were observed within 72 hours after vaccination. The serum samples were collected for the testing of anti-HAV and anti-HBs at month 1, 6 and 7 after initial dose. RESULTS: The local and systemic adverse reactions after immunization were slight and temporary. The rates of local and systemic adverse reactions were 12.1% (14/116) and 6.0% (7/116). The sero-conversion rates of HAV were from 92.9% (92/99) to 100.0% (101/101) and the geometric mean titers (GMT) ranged from 47.0 mIU/ml to 2762.3 mIU/ml 1, 6, 7 months after initial dose. The sero-protection rate of HBV was 86.1% (87/101) before vaccination and came up to 100.0% (101/101) one month after initial dose, and the GMTs of HBV were from 894.3 mIU/ml to 3314.3 mIU/ml 1, 6, 7 months after initial dose. CONCLUSION: The Bilive(TM) combined hepatitis A and hepatitis B vaccine has good safety and immunogenicity in healthy children who had preexisting immunity to hepatitis B virus.

Modeling the Long-term Antibody Response and Duration of Immune Protection Induced by an Inactivated, Preservative-free Hepatitis A Vaccine (Healive) in Children.

OBJECTIVE: Long-term seroprotection via the hepatitis A vaccine is essential for the prevention of disease from the hepatitis A virus (HAV). Due to documented difficulties during decade-long follow-ups after receiving vaccines, statistical-modeling approaches have been applied to predict the duration of immune protection. METHODS: Based on five-year follow-up data from a randomized positive-controlled trial among Chinese children (1-8 years old) following a 0, 6 months vaccination schedule, a power-law model accounting for the kinetics of B-cell turnover, as well as a modified power-law model considering a memory-B-cell subpopulation, were fitted to predict the long-term immune responses induced by HAV vaccination (Healive or Havrix). Anti-HAV levels of each individual and seroconversion rates up to 30 years after vaccination were predicted. RESULTS: A total of 375 participants who completed the two-dose vaccination were included in the analysis. Both models predicted that, over a life-long period, participants vaccinated with Healive would have close but slightly higher antibody titers than those of participants vaccinated with Havrix. Additionally, consistent with previous studies, more than 90% of participants were predicted to maintain seroconversion for at least 30 years. Moreover, the modified power-law model predicted that the antibody titers would reach a plateau level after nearly 15 years post-vaccination. CONCLUSIONS: Based on the results of our modeling, Healive may adequately induce long-term immune responses following a 0, 6 months vaccination schedule in children via induction of memory B cells to provide stable and durable immune protection.

Immunogenicity, safety, and cross-reactivity of an inactivated, adjuvanted, prototype pandemic influenza (H5N1) vaccine: a phase II, double-blind, randomized trial.

BACKGROUND: Avian influenza A virus H5N1 has the potential to cause a pandemic. Adjuvants and whole-virion vaccines are regarded as antigen sparing for pandemic vaccines. METHODS: A double-blind, randomized trial was performed from 28 August to 22 December 2007 in 402 adults; 301 adults were randomly assigned to receive 2 doses of an inactivated, aluminum-adjuvanted, whole-virion H5N1 vaccine containing 5, 10, or 15 microg of hemagglutinin per dose 28 days apart, and 101 of them received 2 doses of 10 microg of vaccine 14 days apart. The vaccine was manufactured from the recombinant A/Vietman/1194/2004 (NIBRG14) strain. Blood samples were collected for hemagglutination inhibition and microneutralization assays. RESULTS: All formulations were well tolerated, with no serious adverse events. Most local and systemic reactions were mild or moderate. Immune responses were induced after 1 dose in all vaccination groups. The highest immune response was seen after 2 doses of 15 microg of vaccine, with 90% and 100% seroconversion rates and 90% and 100% of participants having a titer of > or = 1:40 for hemagglutination inhibition and microneutralization assays, respectively. Both the 10- and 15-microg doses met or exceeded European Union licensure criteria. Generally, higher immune responses were elicited in participants vaccinated 28 days apart than those vaccinated 14 days apart. Cross-reaction assays showed that after 2 doses of 10 microg of vaccine, 98% and 87% of participants had a microneutralization titer of > or = 1:40 against heterologous Indonesia and Anhui strains, respectively. CONCLUSIONS: The inactivated, aluminum-adjuvanted, whole-virion H5N1 vaccine not only showed good immunogenicity and safety but also elicited significant cross-reactivity against heterologous H5N1 strains in clade 2. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00535665.

Safety and immunogenicity from a phase I trial of inactivated severe acute respiratory syndrome coronavirus vaccine.

BACKGROUND: Emergence of severe acute respiratory syndrome (SARS) from the winter of 2002 to the spring of 2003 has caused a serious threat to public health. METHODS: To evaluate the safety and immunogenicity of the inactivated SARS coronavirus (SARS-CoV) vaccine, 36 subjects received two doses of 16 SARS-CoV units (SU) or 32 SU inactivated SARS-CoV vaccine, or placebo control. RESULTS: On day 42, the seroconversion reached 100% for both vaccine groups. On day 56, 100% of participants in the group receiving 16 SU and 91.1% in the group receiving 32 SU had seroconverted. The geometric mean titre of neutralizing antibody peaked 2 weeks after the second vaccination, but decreased 4 weeks later. CONCLUSION: The inactivated vaccine was safe and well tolerated and can elicit SARS-CoV-specific neutralizing antibodies.

Review of 10 years of clinical experience with Chinese domestic trivalent influenza vaccine Anflu®.

Influenza viruses cause annual winter epidemics globally and influenza vaccination is most effective way to prevent the disease or severe outcomes from the illness, especially in developing countries. However, the majority of the world's total production capacity of influenza vaccine is concentrated in several large multinational manufacturers. A safe and effective preventive vaccine for the developing countries is urgent. Anflu®, a Chinese domestic preservative-free, split-virus trivalent influenza vaccine (TIV), was introduced by Sinovac Biotech Ltd. in 2006. Until now, 20.6 million doses worldwide of Anflu® were sold. Since 2003, 13 company-sponsored clinical studies investigating the immunogenicity and safety of Anflu® have been completed, in which 6642 subjects participated and were vaccinated by Anflu®. Anflu® was generally well tolerated in all age groups, and highly immunogenic in healthy adults and elderly and exceeded the licensure criteria in Europe. This review presents and discusses the experience with Anflu® during the past decade. A new Chinese domestic, preservative-free, unadjuvanted, inactivated split-virus trivalent influenza vaccine (TIV), Anflu®, was introduced into human clinical trials in 2003 and then licensed in China in 2006. The vaccine contains 15 µg/0.5 ml hemagglutinin from each of the 3 influenza virus strains (including an H1N1 influenza A virus subtype, an H3N2 influenza A virus subtype, and an influenza B virus) that are expected to be circulating in the up-coming influenza season. The clinical data pertaining to Anflu® will be reviewed and compared with other TIVs available at present.

Immunogenicity, safety, and lot consistency of a novel inactivated enterovirus 71 vaccine in Chinese children aged 6 to 59 months.

The determination of lot-to-lot consistency in the manufacturing process is a mandatory step in the clinical development of the novel enterovirus 71 (EV71) vaccine. A phase III, randomized, placebo-controlled, double-blind trial assessed the lot consistency, immunogenicity, and safety of the EV71 vaccine in children aged 6 to 59 months. Healthy children (n = 1,400) received one of three lots of the EV71 vaccine containing 400 U of EV71 antigen or a placebo at days 0 and 28. Blood samples were collected before dose 1 and at 28 days after dose 2 (day 56) for an anti-EV71 neutralizing antibody (NTAb) assay. The geometric mean titer (GMT) and the seropositivity rates (with titers of ≥1:8) were compared at day 56. After each dose, the solicited injection site and general adverse events (AEs) were recorded for 7 days, and unsolicited AEs were recorded for 28 days. At day 56, the seropositivity rates ranged from 99.7% to 100% for the vaccine groups. The NTAb GMTs for the vaccine were 140.3 (95% confidence interval [CI], 117.8 to 167.1), 141.5 (95% CI, 118.0 to 169.6), and 146.6 (95% CI, 122.5 to 175.3). The two-sided 95% CI of the log difference in GMTs between the pairs of lots were between -0.176 and 0.176, therefore meeting the predefined equivalence criteria. The percentages of subjects reporting any injection site AEs, general AEs, or serious AEs were similar across the four vaccination groups. In conclusion, the demonstration of consistency between the manufacturing lots confirms for the purposes of clinical development the reliability of the EV71 vaccine production process. (This study has been registered at ClinicalTrials.gov under registration no. NCT01636245.).

Review of 10 years of marketing experience with Chinese domestic inactivated hepatitis A vaccine Healive®.

In 2002, the first Chinese domestic preservative-free inactivated hepatitis A vaccine, Healive®, was introduced in China. It is highly immunogenic, and provides lasting protection in healthy individuals and generates protective levels of antibodies in other at-risk individuals. Over 10 years since its first licensure, postmarketing surveillance data have confirmed the outstanding safety profile of the vaccine. Comparative clinical trials indicated that Healive® induce equal or similar immunogenicity with other currently available inactivated hepatitis A vaccines and are interchangeable for the course of HAV immunization in Chinese children. The vaccine is effective in curbing outbreaks of hepatitis A due to rapid seroconversion and the long incubation period of the disease. Additional issues surrounding the use of the vaccine are also reviewed.

Interchangeability and tolerability of two inactivated hepatitis A vaccines in Chinese children.

In China, no data are available to evaluate the interchangeability between Chinese domestic inactivated hepatitis A vaccines (Healive) and imported inactivated hepatitis A vaccines (Havrix). A double-blind, randomized controlled study was to compare interchangeability and safety of Healive and Havrix among Chinese children. Vaccine was administered to 303 healthy children at 0 and 6 months in one of four vaccine regimens: Healive-Healive; Healive-Havrix; Havrix-Healive or Havrix-Havrix. We collected sera samples at 0 (before vaccination), 6 (before second dose) and 7 months (after second dose), and compared groups in terms of proportion of sero-conversions which is defined as ≥ 20 mIU/ml, and geometric mean concentrations (GMCs) of anti-hepatitis A virus (HAV) antibody. Seroconversion rates were 133/133 (100%) for those received one dose of Healive and 105/131 (80.2%) for those received one dose of Havrix at 6 months, respectively (P<0.001), GMCs for Healive and Havrix were 126.1 and 40.9 mIU/ml (P<0.001), respectively. At 7 months, the seroconversion rate was 100% among all groups. The GMC after two doses of Healive was 8905.5 mIU/ml compared with 1900.9 mIU/ml after two doses of Havrix (P<0.001). The GMC in the Healive-Havrix group was 3275.8 mIU/ml compared with 4165.8 mIU/ml in the Havrix-Healive group (P=0.058). There is not different of reported adverse reactions across the groups. The present study indicated that both vaccines can be recommended for interchangeable using of immunization among Chinese healthy children.

[Safety and immunogenicity on the formulation of trivalent split influenza vaccine among healthy people aged over 18 years].

OBJECTIVE: To evaluate the safety and immunogenicity of split influenza vaccine (Anflu(®)). METHODS: An open-labeled clinical trial was carried out in adults aged 18 - 60 years and elders aged over 60 years from August to September, 2010 in Shenyang, Liaoning province. One dose of split influenza vaccine was administered and adverse events were observed. Serum samples were obtained prior to vaccination and 21 days post vaccination. A/H1N1, A/H3N2 and B antibodies against influenza virus were measured using micro-hemagglutination inhibition (HI) assay. RESULTS: A total of 130 subjects were recruited and 120 paired serum samples were obtained. The overall rate of adverse events was 2.3% (3/130) and all of them with systemic reaction. No single serious adverse event was reported. 21 days after the vaccination, the sero-conversion rates of A/H1N1, A/H3N2 and B antibodies against influenza virus among adults were 82.5%, 93.7% and 92.1%, respectively. The Geometric Mean Titer (GMT) ratios were 20.2, 32.0 and 11.4, while the sero-protection rates were 92.1%, 98.4% and 98.4%, respectively. The sero-conversion rates of antibodies among elders were 89.5%, 91.2% and 87.7%, with the GMT ratios as 23.9, 39.8 and 15.1, respectively. The sero-protection rates were 93.0%, 94.7% and 96.5%, respectively. CONCLUSION: All indexes of A/H1N1, A/H3N2 and B antibodies exceeded the licensure criteria established by the EU Committee for Medicinal Products for Human Use, proving the trial vaccine Anflu(®) with good safety and immunogenicity.

Optimal vaccination strategies for 2009 pandemic H1N1 and seasonal influenza vaccines in humans.

A randomized clinical trial was conducted to assess whether the immunogenicity of seasonal and pandemic (H1N1/09) influenza vaccines is affected by the order of vaccine administration. 151 healthy adult volunteers were randomized into three groups. All groups received one dose (15 µg haemagglutinin) each of a pandemic H1N1 vaccine and a seasonal trivalent vaccine. Group 1 received the pandemic H1N1 vaccine first, followed by the seasonal vaccine 21 days later. Group 2 received vaccinations in vice versa and Group 3 received both vaccines simultaneously. Post-vaccination blood samples were collected to determine the immunogenicity by hemagglutination-inhibition (HI), microneutralization (MN), and B cell ELISPOT assays. All three vaccination strategies were well-tolerated and generated specific immune responses. However, we found a significant difference in magnitude of antibody responses to pandemic H1N1 between the three groups. Pre- or co-vaccination with the seasonal flu vaccine led to a significant reduction by 50% in HI titre to pandemic H1N1 virus after pandemic vaccination. Pre- or co-vaccination of pandemic H1N1 vaccine had no effect on seasonal flu vaccination. MN and ELISPOT assays showed a similar effect. Vaccination with pandemic H1N1 vaccine first is recommended to avoid an associated inhibitory effect by the seasonal trivalent flu vaccine.

Safety and immunogenicity of adjuvanted inactivated split-virion and whole-virion influenza A (H5N1) vaccines in children: a phase I-II randomized trial.

OBJECTIVE: Highly pathogenic avian influenza A virus H5N1 has the potential to cause a pandemic. Many prototype pandemic influenza A (H5N1) vaccines had been developed and well evaluated in adults in recent years. However, data in children are limited. Herein we evaluate the safety and immunogenicity of adjuvanted split-virion and whole-virion H5N1 vaccines in children. METHODS: An open-labelled phase I trial was conducted in children aged 3-11 years to receive aluminum-adjuvated, split-virion H5N1 vaccine (5-30 microg) and in children aged 12-17 years to receive aluminum-adjuvated, whole-virion H5N1 vaccine (5-15 microg). Safety of the two formulations was assessed. Then a randomized phase II trial was conducted, in which 141 children aged 3-11 years received the split-virion vaccine (10 or 15 microg) and 280 children aged 12-17 years received the split-virion vaccine (10-30 microg) or the whole-virion vaccine (5 microg). Serum samples were collected for hemagglutination-inhibition (HI) assays. FINDINGS: 5-15 microg adjuvated split-virion vaccines were well tolerated in children aged 3-11 years and 5-30 microg adjuvated split-virion vaccines and 5 microg adjuvated whole-virion vaccine were well tolerated in children aged 12-17 years. Most local and systemic reactions were mild or moderate. Before vaccination, all participants were immunologically naïve to H5N1 virus. Immune responses were induced after the first dose and significantly boosted after the second dose. In 3-11 years children, the 10 and 15 microg split-virion vaccine induced similar responses with 55% seroconversion and seroprotection (HI titer >or=1:40) rates. In 12-17 years children, the 30 microg split-virion vaccine induced the highest immune response with 71% seroconversion and seroprotection rates. The 5 microg whole-virion vaccine induced higher response than the 10 microg split-virion vaccine did. INTERPRETATION: The aluminum-adjuvanted, split-virion prototype pandemic influenza A (H5N1) vaccine showed good safety and immunogenicity in children and 30 microg dose induced immune response complying with European Union licensure criteria.

Antibody persistence after 2-dose priming and booster response to a third dose of an inactivated, adjuvanted, whole-virion H5N1 vaccine.

An inactivated, alum-adjuvanted, whole-virion H5N1 vaccine had been evaluated previously. Hemagglutination inhibition (HI) assays showed that the antibody levels declined significantly, with 4.8%-20.8% and 0%-18.8% of participants retaining seroprotection (HI titer >or=1:40) 6 and 12 months after the second dose, respectively. A third dose of the same vaccine given 12 months after the second dose significantly boosted immune responses. Thirty days after the third dose in the 1.25-, 2.5-, 5-, and 10-microg dose groups, 29.4%, 31.3%, 78.6%, and 90.0% of participants had HI titers >or=1:40, and 52.9%, 81.2%, 92.9%, and 100% of participants had microneutralization titers >or=1:40, respectively. Both the 5-microg and 10-microg doses met European Union criteria.

[Safety and immunogenicity on three lots of influenza split vaccines among adults].

OBJECTIVE: To evaluate the immunogenicity, safety and stability of the manufacture process regarding three consecutive lots of influenza split vaccines (Anflu). METHODS: A double-blind, randomized and controlled clinical trial was conducted in healthy volunteers. A total of 566 subjects aged 18 to 60 years were recruited and stratified into four age groups before randomly assigned into four groups. Each group would receive one dose of influenza vaccine from either one of the three lots of Anflu or one lot of the licensed control vaccine. Each dose of the vaccines contained 15 microg of each of the H1N1, H3N2 and B type antigen. Safety was assessed through 30-minute observation for immediate allergic reaction and three-day observation after vaccination. HI antibody titers were determined before vaccination and on day 21, after vaccination. RESULTS: Mild adverse reaction was reported and the overall incidence rates on fever of the four groups were from 1.4% to 2.8% but no significant difference was observed between groups. Seroconversion rates of the three viral strains in four groups were 80.3% and above with fold increase as > or = 11.1 and protection rate was > or = 93.4%. For the three lots of investigated vaccines, all of the indexes of the three viral strains in four groups exceeded the standards on EMEA and FDA for influenza vaccine. CONCLUSION: The three consecutive lots of Anflu appeared to be good, with both consistent immunogenicity and safety, indicating the stability of manufacture process.

[Immunogenicity and safety of three consecutive lots on an inactivated hepatitis A vaccine: a double-blind, immunogenicity and safety of three consecutive lots on a inactivated hepatitis A vaccine:a double-blind, randomized and controlled trial in children].

OBJECTIVE: To evaluate the immunogenicity, safety, stability and consistency of three consecutive lots of an inactivated hepatitis A vaccine (Healive). METHODS: A double-blind, randomized and controlled clinical trial was conducted in healthy volunteers aged from 1 to 8 years. Totally, 400 subjects were enrolled and assigned into four groups, each receiving one of the three lots of Healive or a licensed control vaccine in 0 and 6th month. Safety was assessed through a 30 minutes and three days observation, thereafter. Anti-HAV titers were determined on the 1st, 6th and 7th month after the vaccination. RESULTS: Seroconversion rate of four groups were all 100% by the end of the schedule while GMTs of Healive were 3237.06-3814.14 mIU/ml but were not significantly different. GMT of control vaccine was 1467.49 mIU/ml. Healive and control vaccine were well tolerated with 1%-5% incidence of overall adverse reactions in which most of them were mild and moderate. No severe adverse reaction was reported. CONCLUSION: The three consecutive lots of Healive were well consistent as indicated by immunogenicity and safety while immunogenicity was better than the vaccine used as control.

Immunogenicity and safety of three consecutive lots of a new preservative-free inactivated hepatitis A vaccine (Healive): a double-blind, randomized and controlled trial.

Immunization is considered as the most effective way for the prophylaxis of hepatitis A virus (HAV) infection. This study aimed to evaluate the immunogenicity and safety of three consecutive lots of a new preservative-free inactivated hepatitis A vaccine (Healive) in healthy children. A double-blind, randomized and controlled clinical trial was conducted in healthy volunteers aged from 1 to 8 years. Total 400 subjects were enrolled and assigned into four groups, receiving one of the three lots of Healive or an established control vaccine. The vaccination was two-dose regimen with 6 months apart. Anti-HAV titers were determined at the 1st, 6th and 7th month. The results showed that Healive was highly immunogenic in children with 100% seroconversion rate (SR) and 3237-3814 mIU/ml geometry mean titer (GMT) 1 month after the second dose. The immunogenicity of Healive was statistically higher than that of the control vaccine with respect to GMT and SR (P=0.037 to P<0.001). Both Healive and control vaccine were well tolerated with 1-5% incidence of overall adverse reactions (P>0.298). Severe adverse reaction was not reported. Both SRs (1, 6 and 7 months) and GMTs (1 and 7 months) in subjects receiving one of the three consecutive lots of Healive had not statistical difference (P=0.114-0.710), suggesting that Healive was well consistent. The immune responses in younger children (1-3 years) and older children (4-8 years) were similar to each other (P=0.187-0.963). The present study indicated that Healive was greatly consistent between production lots, well tolerated and highly immunogenic in children, which made the preservative-free inactivated hepatitis A vaccine well suitable for inclusion in the routine programme of children vaccination.

A serological survey on neutralizing antibody titer of SARS convalescent sera.

A seroepidemiologic study was conducted in North China in 2003 to determine the neutralizing antibody titer of severe acute respiratory syndrome (SARS) convalescent sera. A total of 99 SARS convalescent serum samples were collected from patients from the Inner Mongolia Autonomous Region, Hebei Province, and Beijing 35-180 days after the onset of symptoms. The anti-SARS antibodies were detected by enzyme-linked immunosorbent assay (ELISA), neutralization assay, and Western blot. Eighty-seven serum samples were confirmed to be positive for SARS antibodies. The neutralizing antibody titer of the 87 positive sera was analyzed quantitatively by neutralization assay. The geometric mean titer (GMT) of the 87 convalescent sera was 1:61. The Kolmogorov-Smirnov test showed that the neutralizing antibody titers conform to normal distribution, which suggests that the average anti-SARS antibody level in this study was representative of the convalescent antibody level of the SARS population. This result could be useful for the development and quality control of SARS vaccines.

[Serological investigation on close contacts to patients with severe acute respiratory syndrome in an SARS outbreak].

OBJECTIVE: To study the evidence of severe acute respiratory syndrome (SARS) infection among close contacts to SARS patients and the level of sera IgG antibody in SARS cases. METHODS: Specific IgG antibody against SARS-CoV in serum samples from contacts to patients, five months before an SARS outbreak in Beijing. Neutralized test, ELISA and immunity adherence test were studied. Samples were collected after clinical onset of patients or close contacts to patients, for 22 - 24 weeks. 19 close contacts and 13 cases were included in the study. RESULTS: In close contacts, all tests were negative on three methods. All SARS cases were positive except one by immunity adherence test. The neutralized antibody levels were from 1:16 to 1:203, with medium level of 1:43. CONCLUSION: According to our survey, there was no latent infection among close contacts. IgG antibody in sera continued to be at higher levels among SARS cases 22 - 24 weeks after onset.

[The study on the 0, 12 month vaccination schedule' of Healive inactivated hepatitis A vaccine in children].

OBJECTIVE: To evaluate the safety, immunogenicity and fit dosage of Healive inactivated hepatitis A vaccine (HAV) in children. METHODS: A total of 85 susceptible aged 4 - 10 years with HAV seronegative children, had been enrolled from two adjacent villages in a county. The volunteers were randomized allocated into two groups and to receive a priming dose of 250 U/0.5 ml/dose or 500 U/1.0 ml/dose of Healive vaccine, produced by Sinovac Biotech Co, Ltd. A booster of the same dose was given at 12th month. Local and systemic side effects were examined and seroconversion rate as well as geometric mean titers of anti-HAV antibody were tested at 3-week, 12-month after the primary dose and at 1 month after the booster dose. RESULTS: The vaccine was well tolerated in both groups. At 21 days after the primary dose, the seroconversion rates were 94.4%, 100.0% and geometric mean titers (GMT) were 195 mIU/ml and 370 mIU/ml in 250 U and 500 U groups respectively. At 12 months after the primary dose, the seroconversion rate of anti-HAV was 100.0%, and GMT raised to 361 mIU/ml, 456 mIU/ml (P > 0.05) respectively. One month after the booster dose, GMT raised to 14 893 mIU/ml, 21 696 mIU/ml. CONCLUSION: GMT of the 0, 12 month schedule was higher than other schedule after the booster vaccination. The Healive inactivated vaccine can be used for emergency vaccination. The Healive inactivated vaccine produced by Sinovac Company Ltd was safe and highly immunogenic. Two hundred and fifty U/dose was considered appropriate for children.