Objective: To evaluate the safety and immunogenicity of hepatitis E vaccine(HEV)in Maintenance hemodialysis(MHD)patients. Methods: Based on an open-labeled controlled trial, from May 2016 to March 2018, 35 eligible MHD patients were recruited in the Hemodialysis Center of Zhongshan Hospital Affiliated to Xiamen University as the experimental group, and 70 MHD patients with matched age, gender and underlying diseases as the control group. The experimental group received HEV at 0, 1 and 6 months according to the standard vaccination procedures, while the control group received routine diagnosis and treatment without vaccine and placebo injection to observe the safety and immunogenicity of the vaccine. The safety of vaccine in MHD population was evaluated by the incidence of adverse reactions/events in the experimental and control groups. The immunogenicity of HEV in MHD patients was evaluated by comparing the data from the phase Ⅲ clinical trial. Results: The overall incidence of adverse reactions/events was 17.1% (18/105), and there were no grade 3-4 adverse reactions/events related to vaccination. In the experimental group, the incidence of local adverse reactions/events was 20.0% (7/35), and the incidence of systemic adverse reactions/events was 17.1% (6/35).There was no significant difference in the incidence of systemic adverse reactions/events between the experimental group and the control group (P>0.05). There were 23 patients receiving 3 doses with the standard schedule. The positive rate of HEV-IgG antibody was 100% and the GMC was 14.47(95%CI:13.14-15.80) WU/ml, which showed no significant difference compared with the 46 patients in Phase Ⅲ clinical trial (t=-1.04, P>0.05). Conclusion: Recombinant HEV has good safety and immunogenicity in MHD patients.
Clinical Trials, Phase III as Topic ; Female ; Hepatitis E ; Humans ; Immunogenicity, Vaccine ; Immunoglobulin G ; Male ; Renal Dialysis ; Viral Hepatitis Vaccines/adverse effects*

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

In order to evaluate the familial clustering of hepatitis B virus(HBV) and hepatitis C virus(HCV) infections and to elucidate the possible routes of HCV transmission among Korean adults with chronic liver disease, 137 household contacts of 51 chronic carriers of HBsAg and 111 household contacts of 38 controls, and 181 household contacts of 96 anti-HCV positives and 102 household contacts of 76 anti-HCV negatives were tested from July 1990 to March 1994. Of 71 non-vaccinated household contacts of HBsAg carriers, 10 gave positive result for HBsAg(14.1%), but none of the household contacts of the controls were positive for HBsAg(p< 0.05). Familial clustering of HBV infection was found, when the offspring of carriers and controls were compared. A significantly higher percentage of the offspring of carriers were positive for HBV infection(54.6% vs 15.4%, p< 0.05) with OR of 6.6(95% Cl; 1.3-34.5). No evidence of familial clustering of HCV infection was found with 2.2%(4/181) anti-HCV positivity among the household contacts of index cases, similar to 1.0%(1/102) among those of controls. History of acute hepatitis(OR 3.2), transfusion(OR 3.2), and acupuncture(OR 2.5) were associated with an increased risk of HCV infection. In conclusion, HBV has strong familial clustering whereas HCV does not in Korea.
Acupuncture Therapy/adverse effects ; Adolescent ; Adult ; Aged ; Biological Markers ; Blood Transfusion/adverse effects ; Carrier State ; Child ; Child, Preschool ; Cluster Analysis ; Comorbidity ; Comparative Study ; Contact Tracing ; *Family Health ; Female ; Hepatitis B/*epidemiology/prevention & control/transmission/virology ; Hepatitis B Antibodies/blood ; Hepatitis B Core Antigens/blood ; Hepatitis B Surface Antigens/blood ; Hepatitis C/*epidemiology/prevention & control/transmission/virology ; Human ; Infant ; Korea/epidemiology ; Male ; Middle Age ; Postoperative Complications/epidemiology ; Prevalence ; Risk Factors ; Seroepidemiologic Studies ; Sexually Transmitted Diseases/epidemiology ; Support, Non-U.S. Gov't ; Viral Hepatitis Vaccines

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