OBJECTIVETo evaluate the immunogenicity, safety, and dosage of a new inactivated hepatitis A vaccine administered to young adults.

METHODSOne hundred and four normal adult volunteers, seronegative for hepatitis A virus and hepatitis B surface antigen, were randomly assigned to one of three groups. The high-dose group received a primary dose of 1000 units of the new vaccine, the low-dose group received a primary dose of 500 units of the same vaccine, and the Havrix group received a primary dose of 1440 enzyme-linked immunosorbent assay units of Havrix, a licensed inactivated hepatitis A vaccine. All groups received a booster dose of the same vaccine 6 months after the primary dose. Local and systemic adverse reactions, seroconversion rates, and geometric mean titers of hepatitis A virus antibodies were measured in all three groups.

RESULTSLocal and systemic reaction types and rates were similar in all three groups after primary and booster doses, although local reactions were more frequent in the Havrix group following the primary dose. No serious adverse reactions occurred. One month after the primary dose, the seroconversion rate was 87.5% in the high-dose group, 70.0% in the low-dose group, and 50.0% in the Havrix group (P = 0.001, versus the high-dose group). At month 6 (before administration of the booster dose), seroconversion rates were 96.9% in the high-dose group, 65.0% in the low-dose group (P = 0.0029), and 68.8% in the Havrix group (P = 0.007). All subjects in all groups seroconverted by one month after receipt of the booster dose. Geometric mean titers were similar in all three groups at month 1, but were higher in the high-dose group (264 mIU/ml) than those in the Havrix group (135 mIU/ml) at month 6 (P = 0.0013). One month after the booster dose, geometric mean titers in the high-dose group (2747 mIU/ml) were higher than those in the low-dose group (1657 mIU/ml) (P = 0.0223) or in the Havrix group (1316 mIU/ml) (P = 0.01).

CONCLUSIONSThis new inactivated hepatitis A vaccine is immunogenic and safe; two doses of either 500 or 1000 units can induce hepatitis A virus antibodies well above the protection level.

Adolescent ; Adult ; Hepatitis A Vaccines ; adverse effects ; immunology ; Humans ; Vaccines, Attenuated ; adverse effects ; immunology

Biomedical Research ; China ; Freeze Drying ; Hepatitis A Vaccines ; adverse effects ; immunology ; Humans ; Safety ; Vaccines, Attenuated ; adverse effects ; immunology

Child, Preschool ; China ; Female ; Hepatitis A ; immunology ; prevention & control ; Hepatitis A Antibodies ; blood ; Hepatitis A Vaccines ; adverse effects ; immunology ; Humans ; Infant ; Male ; Safety ; Sampling Studies ; Vaccination ; Vaccines, Inactivated ; adverse effects ; immunology

Although the overall incidence of hepatitis A in Korea has been decreasing, adolescents remain highly vulnerable to its outbreaks. This study was conducted to compare the immunogenicity and safety of three hepatitis A vaccines in Korean adolescents. Healthy anti-hepatitis A virus seronegative subjects aged 13 to 19 yr were randomized in three equal groups to receive two doses of Avaxim(TM), Epaxal(R), or Havrix(R), 6 to 12 months apart. Seroconversion rates one month after the first dose were 98%, 95%, and 93% for Avaxim(TM), Epaxal(R), and Havrix(R), respectively. Seroconversion rates reached 100% for all vaccine groups one month after the second dose. Anti-HAV geometric mean concentrations (GMCs) were 7,207.7 mIU/mL (95% CI, 6023.1-8684.7), 1,750.5 mIU/mL (95% CI, 1362.9-2248.3), and 1,953.5 mIU/mL (95% CI, 1459.4-2614.7) after two doses of Avaxim(TM), Epaxal(R), and Havrix(R) respectively. Avaxim(TM) was significantly more immunogenic than Epaxal(R) and Havrix(R), whereas there were no significant differences in antibody responses between Epaxal(R) and Havrix(R). Local and systemic solicited adverse events (AEs) were mostly of mild-to-moderate intensity and resolved within 5 days. No serious AEs were reported. In conclusion, all three vaccines are highly immunogenic and well-tolerated in Korean adolescents. (Clinical Trial Registry NCT00483470)
Adolescent ; Antibody Formation ; Female ; Hepatitis A/immunology/*prevention & control ; Hepatitis A Antibodies/blood ; Hepatitis A Vaccines/adverse effects/*immunology ; Humans ; Male ; Republic of Korea ; Vaccines, Inactivated/adverse effects/immunology ; Young Adult

OBJECTIVETo study the safety and immunogenicity of the Bilive combined hepatitis A and B vaccine produced by Sinovac Biotech Co., Ltd.

METHODSSamples were selected from first year students of a senior high school (adults group) and first to fifth grade 1-5 students of 3 primary schools (children group). Those who were susceptible to both hepatitis A virus (HAV) and hepatitis B virus (HBV), HAV only or HBV only were assigned to group AB, A and B respectively and were vaccinated with three doses (0, 1 and 6 month schedule) of Bilive combined hepatitis A and B vaccine, inactivated hepatitis A vaccine and recombined hepatitis B vaccine respectively. The dosage for adult group was 500 U hepatitis A antigen and/or 10 micro g hepatitis B surface antigen and the dosage for children group was half the dosage of adult group. The potential adverse effects were observed within 72 hours after vaccination. Serum samples were collected for testing anti-HAV and anti-HBs at month 2 and 7 after the initial dose.

RESULTSThe rates of local adverse effects were 0.58% and 2.56% in children AB group and adults AB group and the general adverse effects rates were 9.88% and 5.45% respectively. Both local and general adverse effect rates were not significantly different to the control group. The sero-conversion rate of anti-HAV in children and adults AB group reached 100%, one month after 3 doses. The geometric mean titer (GMTs) reached 33,910 mIU/ml and 23,435 mIU/ml respectively, significant higher than that in control group (group A). The sero-conversion rates of anti-HBs were 97.30% and 96.63%, and GMTs were 103 mIU/ml and 102 mIU/ml in children and adults AB group respectively. No significant difference on sero-conversion and GMT was observed when compared with control group.

CONCLUSIONThe Bilive combined hepatitis A and B vaccine had good safety profile, and the immunogenicity both on anti-HAV and anti-HBs was similar to that of separated components.

Adolescent ; Adult ; Child ; Female ; Hepatitis A ; prevention & control ; Hepatitis A Antibodies ; blood ; Hepatitis A Vaccines ; administration & dosage ; adverse effects ; immunology ; Hepatitis Antibodies ; blood ; Hepatitis B ; prevention & control ; Hepatitis B Antibodies ; blood ; Hepatitis B Vaccines ; administration & dosage ; adverse effects ; immunology ; Humans ; Male ; Safety ; Vaccines, Combined ; administration & dosage ; adverse effects ; immunology ; Vaccines, Synthetic ; administration & dosage ; adverse effects ; immunology

OBJECTIVETo evaluate the safety and immunogenicity of the Bilive(TM) combined hepatitis A and hepatitis B vaccine in healthy children.

METHODSA 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.

RESULTSThe 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.

CONCLUSIONThe 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.

Child ; Child, Preschool ; Dose-Response Relationship, Immunologic ; Female ; Hepatitis A Vaccines ; adverse effects ; immunology ; Hepatitis B Vaccines ; adverse effects ; immunology ; Humans ; Immunization Schedule ; Infant ; Male ; Vaccines, Combined ; adverse effects ; immunology

OBJECTIVETo assess the feasibility of the 10 microg recombination yeast hepatitis B vaccine in the expanded applicable population group aged 5 - 18.

METHODSPeople with both HBsAg and anti-HBs negative were selected to take two-stage clinical experiment and the safety and immunogenicity were observed. Safety observation was conducted in 925 subjects, while 568 for immunogenicity. The observation group (aged 5 - 18) included 493 subjects, and (age > 18) 75 enrolled in control group. For the observation group, there were three sub-groups including a child group (141, aged 5 - 6), early youth group (177, aged 12 - 13), and youth group (175, aged 16 - 18). Both groups were administered with 10 microg recombination yeast hepatitis B vaccines with 3 doses at 0 month, 1st month, 6th month. To assess the immunogenicity, the vaccination reactions were observed during the following 4 weeks in order to assess the vaccine safety. The blood samples were taken during 4 - 6 weeks after fully vaccinated, and then anti-HBs were tested with RIA and analyzed by comparing the positive rate of anti-HBs, the geometric mean titer (GMT) and the protective rate between the two groups.

RESULTSBoth observation and control group didn't show any general reactions, adverse events following immunization (AEFI) or coincidental cases when observed at 0.5 h, 6 h, 24 h, 48 h, 72 h, 1 week, 2 weeks, 3 weeks, 4 weeks after being vaccinated. The result of serum test showed, the positive rates of child group, early youth group, youth group and control group were respectively 100.00% (141/141), 97.18% (172/177), 98.29% (172/175) and 89.33% (67/75); the GMTs of anti-HBs were respectively 440.28, 875.38, 467.80, 131.06 U/L; the protective rates were respectively 100.00% (141/141), 97.18% (172/177), 97.14% (170/175) and 86.67% (65/75). The positive rate, GMT and protective rate of the experimental group were all higher than that of control group (chi(2)(positive rate) = 12.77, 5.12, 7.99; t(GMT) = 3.89, 4.13, 5.91; chi(2)(protective rate) = 16.81, 8.60, 8.44; P < 0.05).

CONCLUSIONThis vaccine could be expanded to 5 - 18 year-old population with safety and effectiveness, the positive rate and protective rate of anti-HBs were both higher than that of control group.

Adolescent ; Child ; Child, Preschool ; Female ; Hepatitis B Antibodies ; blood ; immunology ; Hepatitis B Surface Antigens ; blood ; immunology ; Hepatitis B Vaccines ; administration & dosage ; adverse effects ; immunology ; Humans ; Male ; Vaccines, Synthetic ; administration & dosage ; adverse effects ; immunology

OBJECTIVETo study the effect and mechanism of the peripheral blood mononuclear cell (PBMC) invasion by HBV on artificial immunization in newborns.

METHODSFifty-two newborns of HBsAg positive mothers were immunized with HBIG (hepatitis B immunoglobulin) and HBVac (hepatitis B vaccine) and were followed up for 7 months. The newborns' HBV-DNA in serum and in the PBMCs was detected with nested-PCR; anti-HBs was tested with solid phase radioimmunoassay (SP-RIA). PBMCs isolated from newborn peripheral blood were incubated in the presence of PHA or purified HBsAg. Interleukin-2 (IL-2) level in culture supernatants of activated cells was detected by ELISA.

RESULTSThe failure rate of immunization was higher in infants with positive HBV-DNA in PBMCs than those with negative HBV-DNA (P < 0.05); IL-2 level in PBMC culture supernatants was lower in former than in the latter and in normal controls (P < 0.05). The level of IL-2 in the immunization failure newborns was lower than that in the successfully immunized newborns and in normal controls (P < 0.05).

CONCLUSIONSIntrauterine invasion of PBMCs by HBV is one of the important reasons for immunization failure in newborns. IL-2 production is closely related to the invasion of PBMCs by HBV, which may contribute to the failure of artificial immunization in newborns.

DNA, Viral ; blood ; Hepatitis B Surface Antigens ; immunology ; Hepatitis B Vaccines ; adverse effects ; Hepatitis B virus ; isolation & purification ; physiology ; Humans ; Immunization ; adverse effects ; Immunoglobulins ; immunology ; Infant, Newborn ; Interleukin-2 ; biosynthesis ; blood ; Leukocytes, Mononuclear ; virology

The human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine has been demonstrated to be highly efficacious and immunogenic with a favorable safety profile. This study assessed the immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in healthy Korean girls aged 10-14 yr. This multi-center, observer-blind trial randomly assigned 321 healthy girls to receive three doses (0, 1, 6-month schedule) of HPV-16/18 AS04-adjuvanted vaccine or hepatitis A vaccine. Immunogenicity against vaccine antigens was assessed one month post-Dose 3. Solicited and unsolicited adverse events (AEs) and serious AEs (SAEs) were recorded. In the according-to-protocol analysis, all initially seronegative subjects vaccinated with the HPV-16/18 AS04-adjuvanted vaccine had seroconverted at Month 7, with a peak geometric mean titer (GMT) that was 600-fold higher than the natural infection titer of 29.8 EU/mL for HPV-16 and a peak GMT that was 400-fold higher than the natural infection titer of 22.6 EU/mL for HPV-18. The vaccine was well tolerated with no increase in reactogenicity with subsequent doses and no reports of vaccine-related SAEs. In conclusion, the HPV-16/18 AS04-adjuvanted vaccine is shown to be highly immunogenic and generally well-tolerated in Korean girls aged 10-14 yr.
Adjuvants, Immunologic/administration & dosage ; Adolescent ; Aluminum Hydroxide/administration & dosage ; Antibodies, Viral/analysis ; Child ; Female ; Hepatitis A/immunology ; Hepatitis A Vaccines/administration & dosage/adverse effects/immunology ; Humans ; Lipid A/administration & dosage/analogs & derivatives ; Papillomavirus Infections/*prevention & control ; Papillomavirus Vaccines/administration & dosage/adverse effects/*immunology ; Republic of Korea ; Seroepidemiologic Studies ; Uterine Cervical Neoplasms/*prevention & control

The S protein of hepatitis B virus is the principal component of virus envelope and the primary target of anti-HBs response. Mutants or variants that escape neutralization by anti-HBs have been selected during immunoprophylaxis of HBV after birth and liver transplantation. We investigated a case of a Korean child who was vaccinated at birth against hepatitis B and also given hepatitis B immunoglobulin, but nevertheless later became infected with the virus. Hepatitis B virus-specific deoxyribonucleic acid covering the region of genome encoding the predominant "a" determinant of hepatitis surface antigen was amplified using polymerase chain reaction, and the nucleotide sequence was determined. We present for the first time in Korea the independent emergence of an escape mutant with substitution of arginine for glycine at amino acid 145 and proline for glutamate at amino acid 120 in "a" determinant after immunization.
Cloning, Molecular ; DNA, Viral/analysis ; Epitopes, B-Lymphocyte/genetics ; Hepatitis B Surface Antigens/*genetics/immunology ; Hepatitis B Vaccines/*adverse effects/genetics/immunology ; Hepatitis B Virus/*genetics/immunology ; Hepatitis B e Antigens/blood ; Human ; Infant ; Korea ; Male ; Mutagenesis, Site-Directed ; *Mutation ; Polymerase Chain Reaction/methods ; Sequence Analysis, DNA