Clinical study of hepatitis B vaccine in achieving hepatitis B surface antibody seroconversion in patients with functional cure

Abstract Hepatitis B Surface Antigen (HBsAg) seroclearance is the highest treatment goal recommended by the current guidelines for hepatitis B. Levels of antibodies to HBsAg (anti-HBs) are strongly associated with HBsAg recurrence, but hepatitis B vaccination may increase the anti-HBs seroconversion rate and reduce recurrence. We conducted a retrospective clinical study to ascertain the effect of this vaccination on the seroconversion rate and levels of protective anti-HBs after HBsAg. In this retrospective study, we distributed a questionnaire through an online survey platform to collect information related to hepatitis B vaccination in patients with functional cure of hepatitis B with Interferon-α (IFNα) therapy. We enrolled 320 patients who achieved functional cure from IFNα therapy. Of these, 219 patients had received hepatitis B vaccination according to their personal preference and drug accessibility after HBsAg seroclearance, whereas the remaining 101 patients did not receive hepatitis B vaccination. The anti-HBs seroconversion rate of 78.1% in the vaccinated group was significantly greater than that in the unvaccinated group (41.6%) (p < 0.001). Stratified comparisons with anti-HBs of ≥ 100 IU/L and ≥ 300 IU/L showed that both proportions in the vaccinated group were greater than those in the unvaccinated group (71.2% vs. 32.7% and 56.2% vs. 17.8%, respectively, all p-values < 0.001). Logistic regression analysis showed that the odds ratio of vaccination was 4.427, which was the strongest influencing factor for anti-HBs, reaching 100 IU/L or higher. Hepatitis B vaccination in patients after HBsAg seroclearance not only increased the anti-HBs seroconversion rate but also significantly increased antibody levels, with good safety, indicating the clinical value of vaccine therapy for patients with functional cure.

Detection of serum antibody levels after inoculation of an inactivated SARS-CoV-2 vaccine / 预防医学

Objective @#To investigate the serum levels of antibodies against SARS-CoV-2 after inoculation of an inactivated SARS-CoV-2 vaccine, so as to provide insights into the evaluation of the vaccine immunogenicity. @*Methods @#In this single-arm Objective performance criteria trial, residents aged 18 to 59 years and inoculated with an inactivated SARS-CoV-2 vaccine in Xihu District, Hangzhou City from October to December of 2020 were selected using a cluster sampling method. Blood samples were collected prior to inoculation, 14 and 28 days post-inoculation of the first dose, and 28 days post-inoculation of the second dose. Serum levels of anti-SARS-CoV-2 IgM and IgG antibodies were detected using the magnetic particle-based chemiluminescence immunoassay. The seroconversion of antibodies and dynamic changes of antibody levels were analyzed.@*Results @#Totally 310 participants were enrolled, including 133 subjects on day 14 post-inoculation of the first dose, 97 subjects on day 28 post-inoculation of the first dose and 254 subjects on day 28 post-inoculation of the second dose. The seroconversion rates of anti-SARS-CoV-2 IgG antibody were 6.02%, 28.87% and 98.43%, and the median IgG antibody levels were 1.76 ( interquartile range, 3.25 ), 5.69 ( 9.95 ) and 52.05 ( 47.60 ) AU/mL ( P<0.05 ), respectively, while the seroconversion rates of anti-SARS-CoV-2 IgM antibody were 9.02%, 11.34% and 12.99%, and the median IgG antibody levels were 1.89 ( 3.28 ), 2.06 ( 4.71 ) and 2.65 ( 4.01 ) AU/mL ( P>0.05 ), respectively. In addition, higher serum levels of anti-SARS-CoV-2 IgG and IgM antibodies were detected post-inoculation relative to pre-inoculation ( P<0.05 ), and higher serum IgG antibody levels were found in subjects aged 18 to 39 years than in those aged 40 to 59 years ( P<0.05 ). @*Conclusions @#Inoculation of two doses of the inactivated SARS-CoV-2 vaccine achieves a high immunogenicity among residents aged 18 to 59 years 28 days post-inoculation, and the anti-SARS-CoV-2 IgM antibody is detectable in some residents following inoculation of the first dose.

Seroprevalence and seroconversion rates to SARS-CoV-2 in interns, residents, and medical doctors in a University Hospital in Bogotá, Colombia / Tasas de seroprevalencia y seroconversión al SARS-CoV-2 en internos, residentes y médicos en un Hospital Universitario de Bogotá, Colombia

Abstract Objectives: To determine the prevalence of antibodies to SARS-CoV-2 and the incidence of seroconversion in the first month of follow-up among interns, residents, and medical doctors attending patients at a University Hospital in Bogota (Colombia). Design or methods: A cross-sectional and a prospective study were performed during June, July, and August 2020 to assess seroprevalence and seroconversion rates using CLIA IgG for SARS-CoV-2. LFA IgG and IgM and ELFA IgM were also determined to explore concordance with CLIA IgG. Results: At baseline, 8 (2.28% 95%CI 1.16-4.43%) participants were IgG positive for SARS-CoV-2 by CLIA. At the end of the study, 21 (5.98% 95%CI 3.94-8.97%) individuals seroconverted by CLIA IgG. In all, 29 individuals had IgG by CLIA and of these 11 (3.13% 95%CI 1.76-5.52%) were asymptomatic. No associations with risk factors for infection were identified. CLIA IgG had moderate concordance (>962 samples) with LFA IgG and ELFA IgM, but minimal with LFA IgM. Conclusions: Our report is the first in Latina America on seroprevalence and seroconversion rates in medical healthcare workers. The relatively high rate (>3%) of asymptomatic health care workers with evidence of previous SARS-CoV-2 infection underscores the need to screen this population for infection to prevent infection/disease spread.

Resumen Objetivos: Determinar la prevalencia de anticuerpos frente al SARS-CoV-2 y la incidencia de seroconversión en el primer mes de seguimiento en internos, residentes y médicos que atienden pacientes en un Hospital Universitario de Bogotá (Colombia). Diseño y métodos: Se realizó un estudio transversal y prospectivo durante junio, julio y agosto de 2020 para evaluar las tasas de seroprevalencia y seroconversión utilizando CLIA IgG para SARS-CoV-2. También se determinaron LFA IgG e IgM y ELFA IgM para explorar la concordancia con CLIA IgG. Resultados: Al inicio del estudio, 8 (2,28% IC del 95% 1,16-4,43%) participantes fueron IgG positivos para SARS-CoV-2 por CLIA. Al final del estudio, 21 (5,98% IC 95% 3,94-8,97%) individuos seroconvirtieron por CLIA IgG. En total, 29 individuos tenían IgG por CLIA y de estos 11 (3,13% 95% IC 1,76-5,52%) eran asintomáticos. No se identificaron asociaciones con factores de riesgo de infección. El CLIA IgG tuvo una concordancia moderada (> 962 muestras) con LFA IgG y ELFA IgM, pero mínima con el LFA IgM. Conclusiones: Nuestro informe es el primero en América Latina sobre tasas de seroprevalencia y seroconversión en trabajadores médicos de la salud. La tasa relativamente alta (> 3%) de trabajadores de la salud asintomáticos con evidencia de infección previa por SARS-CoV-2 resalta la necesidad de realizar pruebas de detección de infección en esta población para prevenir la propagación de la infección.

Immunogenicity of quadrivalence recombinant human papillomavirus vaccine (6, 11, 16 and 18 types) (Hansenulapolymorpha): results from phaseⅠ clinical trial / 中华微生物学和免疫学杂志

Objective@#To make a preliminary assessment on the immunogenicity of a quadrivalence recombinant human papillomavirus (HPV) vaccine (6, 11, 16 and 18 types) (Hansenulapolymorpha) in healthy women aged 18-45 years in phaseⅠclinical study.@*Methods@#It was a single-center, double-blind, randomized, placebo-controlled phaseⅠ clinical study. Women aged 18-45 years were randomized (2∶1) to receive HPV vaccine (n=60) or placebo control (n=30) at months 0, 2 and 6. Antibodies against HPV6/11/16/18 were detected by pseudovirus-based neutralisation assay in serum samples collected at 0 d, 180 d and 210 d. Seroconversion rates and geometric mean titres (GMT) of antibodies against the four types of antigens were calculated.@*Results@#Seroconversion rates of the vaccination group at 180 d (before the third dose) and 210 d (one month after the third dose) were generally similar and between 85%-100% for all types of antibodies. The GMT of antibodies at one month after the last dose improved significantly compared with those before immunization.@*Conclusions@#These results showed that the HPV vaccine had good immunogenicity in the population of healthy women aged 18-45 years. Higher antibody titers were elicited by the vaccine compare with the tites before the first dose and in the placebo control group.

Immunogenicity of quadrivalence recombinant human papillomavirus vaccine ( 6, 11, 16 and 18 types) ( Hansenulapolymorpha):results from phaseⅠ clinical trial / 中华微生物学和免疫学杂志

Objective To make a preliminary assessment on the immunogenicity of a quadriva-lence recombinant human papillomavirus (HPV) vaccine (6, 11, 16 and 18 types) (Hansenulapolymor-pha) in healthy women aged 18-45 years in phaseⅠclinical study. Methods It was a single-center, doub-le-blind, randomized, placebo-controlled phaseⅠclinical study. Women aged 18-45 years were randomized (2 : 1) to receive HPV vaccine (n=60) or placebo control (n=30) at months 0, 2 and 6. Antibodies against HPV6/11/16/18 were detected by pseudovirus-based neutralisation assay in serum samples collected at 0 d, 180 d and 210 d. Seroconversion rates and geometric mean titres ( GMT) of antibodies against the four types of antigens were calculated. Results Seroconversion rates of the vaccination group at 180 d ( be-fore the third dose) and 210 d ( one month after the third dose) were generally similar and between 85％-100％ for all types of antibodies. The GMT of antibodies at one month after the last dose improved signifi-cantly compared with those before immunization. Conclusions These results showed that the HPV vaccine had good immunogenicity in the population of healthy women aged 18-45 years. Higher antibody titers were elicited by the vaccine compare with the tites before the first dose and in the placebo control group.

Safety and Immunogenicity Assessment of an Oral Cholera Vaccine through Phase I Clinical Trial in Korea

The safety, tolerability and immunogenicity of an oral cholera vaccine (OCV) was assessed in adult Korean male through an open-label, non-comparative clinical study. Two doses of vaccine with an interval of 2 weeks were given to 20 healthy subjects. A total of 7 adverse events occurred in 6 subjects. However, no clinically significant change was observed in electrocardiograms, vital signs, physical examinations, and clinical laboratory tests. The immunogenicity of OCV was evaluated by serum vibriocidal assay where anti-Vibrio cholerae O1 and O139 antibodies were measured at day 0, 14, and 28 of vaccine administration. The antibody titers ranged from < 2.5-5,120 for V. cholerae O1 Inaba, < 2.5-10,240 for V. cholerae O1 Ogawa and < 2.5-480 for V. cholerae O139. In addition, the fold increase in antibody titers ranged from 1-4,096 for O1 Inaba, 1-8,192 for O1 Ogawa, and 1-384 for O139. The seroconversion rate was 95% and 45% for O1 and O139 antibodies, respectively. Our study clearly shows that administration of two doses of OCV at a 2 week-interval increases an appropriate level of antibody titer in the serum of healthy Korean adult males (Clinical Trial Number, NCT01707537).

The Seroprevalence Rate, Vaccination Rate and Seroconversion Rate of Hepatitis A in Central Region of Korea / 대한소화기학회지

BACKGROUND/AIMS: Acute hepatitis A (HAV) is markedly increasing recently on. Some patients with acute hepatitis A show severe clinical course. The seroprevalence rate of IgG anti-HAV has been changing with the regions and the times. Vaccination and seroconversion rate of HAV are not well known. In this study, we aimed to study the difference of seroprevalence rate of IgG anti-HAV according to various clinical factors and to know the vaccination rate and seroconversion rate below 10 years old in the central region of South Korea including Cheonan city. METHODS: Seven hundred seventy two subjects were included in the study from January to September 2009. We analyzed seroprevalence rate of IgG anti-HAV according to sex, age, region, and other viral markers. We interviewed the history of vaccination(1st, 2nd) and analyzed seroconversion rate according to vaccination time below 10 years old. RESULTS: The total seroprevalence rate of IgG anti-HAV was 65.3%. The seroprevalence rate of IgG anti-HAV rate in 2nd, 3rd, and 4th decade was very low (1.9%, 18.8%, 44.8%). The vaccination rate of children was about 50%. The seroconversion rate after 1st, and 2nd vaccination were 85%, 96%. CONCLUSIONS: Catch-up vaccination for teenagers and young adults is needed. Immunizing children with HAV vaccine as a routine schedule should be considered.

Natural History of Chronic Hepatitis B in Children / 소아과

PURPOSE: We investigated the spontaneous seroconversion rate of hepatitis B viral markers and predictive factors affecting seroconversion in children with chronic hepatitis B. METHODS: The study population included 214 children diagnosed as chronic hepatitis B, with positive HBsAg, HBeAg and HBVDNA over six months, and all patients had a family history of chronic Hepatitis B. They were followed between May 1982 and Febrary 2003 in the Department of Pediatrics, Yonsei University College of Medicine. Serum HBsAg, HBeAg, anti-HBs, HBVDNA, and AST/ALT were measured every six months. RESULTS: The mean age of patients was 7.4+/-4.5 years. The loss of HBeAg, HBVDNA and HBsAg were observed in 44(19.2%), 34(15.9%) and 3(1.4%) children respectively. The patients with serum ALT levels over three times normal and with HBVDNA less than 1,000 pg/dL showed significantly higher seroconversion rates of HBeAg and HBVDNA(P<0.001). By analyzing with the life table method, the cumulative seroconversion rate of HBeAg was 11% at 10 and 35% at 19 years of age, while HBVDNA was 9% at 10 and 32% at 19 years of age. In cases of HBsAg, the cumulative seroconversion rate was only 1.5% at 19 years of age. The age of patients, serum ALT and HBVDNA levels were proven as signifincant factors influencing the seroconversion of HBeAg and HBVDNA(P<0.001). CONCLUSION: In children with chronic hepatitis B, the seroconversion rate of HBeAg and HBVDNA are expected to be 35% and 32%, respectively, by the age of 19 years. The age of patients, serum ALT and HBVDNA levels seem to have significant influence on HBeAg and HBVDNA seroconversion.

Factors influencing on the seroconversion of anti-HBs in the subjects with isolated anti-HBc

BACKGROUND: Korea is an endemic area of viral hepatitis B. In spite of the HBV vaccination program since 1983, the prevalence of HBV antigen had remained high, which was 3.9% in male, 2.7% in female in 1994. But there is no approved management guideline on isolated anti-HBc and the meaning of which is not clear except the evidence of past infection. Therefore, we tried to investigate the factors which influence the seroconversion of anti-HBs during follow-up period. METHODS: Medical records of 239 subject with isolated anti-HBc, who visited a health promotion center from 1995 to 1997 and who were retested at least once during the 1-3 years' follow-up period, were analyzed. RESULTS: The seroconversion rate of anti-HBs was 45.61%(109/239) on the follow-up test. The number of newly vaccinated or non-newly vaccinated subjects during the follow-up period was 156 and 72, respectively. The seroconversion rate of anti-HBs of each group were 57.69%(90/156) and 22.22% (16/72) respectively(p<0.01). The subjects without previous history of HBV vaccination was 103. Among them the seroconversion rate of anti-HBs of the newly vaccinated or the non newly vaccinated group were 59.70%(40/67) and 22.22% (8/36), respectively(p<0.01). Sex, age, BMI, smoking, previous history of HBV vaccination did not influence significantly on the seroconversion rate of anti-HBs among the subjects with isolated anti-HBc. CONCLUSIONS: The seroconversion rate in people with isolated anti-HBc was significantly higher in the newly vaccinated than the non-newly vaccinated regardless of the previous history of HBV vaccination in this study. In spite of the non-differentiation of an-amnestic response from primary antibody response, we can expect to benefit from HBV vaccination in those with isolated anti-HBc.59.70%(40/67) and 22.22% (8/36), respectively(p<0.01). Sex, age, BMI, smoking, previous history of HBV vaccination did not influence significantly on the seroconversion rate of anti-HBs among the subjects with isolated anti-HBc. CONCLUSIONS: The seroconversion rate in people with isolated anti-HBc was significantly higher in the newly vaccinated than the non-newly vaccinated regardless of the previous history of HBV vaccination in this study. In spite of the non-differentiation of an-amnestic response from primary antibody response, we can expect to benefit from HBV vaccination in those with isolated anti-HBc.

Effect of Simultaneous Administration of Hepatitis B Vaccine with DPT and Oral Polio Vaccine

PURPOSE: The universal vaccination against hepatitis B during early infancy is the only effective way to control hepatitis B infection in highly endemic areas in Korea. The purpose of this study was to assess the effectiveness of simultaneous hepatitis B vaccination with DPT and oral polio at 2, 4, 6 months of age in babies of HBs antigen negative mothers. METHODS: One hundred and eighty-one infants who were admitted to the Neonatal Intensive Care Unit (NICU), Chonnam University Hospital from August, 1994 to December, 1995 were enrolled in this study. Infants received Hepavax-B 0.5ml (10 microgram) at contralateral thigh intramuscularly, simultaneously with DPT vaccination. Antibody was assessed by MEIA (microparticle enzyme immunoassay) at seven to nine months of age. RESULTS: The seroconversion rate of Hepatitis B after vaccination was 98.3%. There were no significant differences in positive rate of antibody according to gestational age, birth weight and sex. Seroconversion rate to hepatitis B in twins was lower than in singlets. Twenty-two infants among 23 infants, who were able to assess antibody titer, showed effective antibody titer, above 100mIU/ml. CONCLUSION: The results suggest that the simultaneous administration of hepatitis B vaccine with DPT/TOPV is very effective and simplifies schedule. Moreover, this schedule will improve the compliance of vaccination.