High chance to overcome the non-responder status to hepatitis B vaccine after a further full vaccination course: results from the extended study on healthcare students and workers in Florence, Italy.
ABSTRACT: Healthcare workers (HCWs) are considered high-risk subjects for Hepatitis B Virus (HBV) infection due to occupational exposure to blood and body fluids. Vaccination represents the core strategy for HBV infection prevention. Following our previous publication on this topic, we aimed to assess the effectiveness of booster vaccine doses in eliciting the immunological response in seronegative (<10 mIU/mL) HCWs and students of Careggi Teaching Hospital, Florence (Italy). All subjects received primary vaccination course, and they were tested for serum anti-HBs antibodies. In seronegative subjects, a challenge dose of vaccine was administered and the test was repeated 1 month later. Six hundred and ninety-eight (87.8%) of 795 HCWs and students tested responded to the challenge dose. After this challenge dose, males more often had negative anti-HBs titer compared with females (15.9% vs 10.2%; p < .05). The completion of the second vaccination course was offered to subjects with persistently negative anti-HBs titer. 76.2% (32) of those who accepted the fifth dose, and 3 of the 5 who accepted the sixth dose seroconverted. This report shows the importance to convey a strong message to negative subjects at the initial anti-HBs dosage: accepting all the three additional vaccine doses allows the vast majority of them to obtain protection.
Project description:Health Care Workers (HCWs) have an increased risk of contracting contagious disease, including mumps. In January 2017 the Italian National Vaccine Prevention Plan 2017-2019, recommended the administration of a dose of MMR vaccine (Measles-Mumps-Rubella) to the Health Care Workers (HCWs) that, working in a risky environment, did not carry out the complete vaccination cycle of MMR or that are seronegative for at least one of the three vaccine viruses. In October of the same year, the Advisory Committee on Immunization Practices (ACIP) recommended a third dose of a vaccine containing Mumps Virus for people previously vaccinated with 2 doses, belonging to a group or to a population at increased risk of acquire mumps in the event of an epidemic. We analyzed the clinical records and values of mumps-specific IgG antibodies of 3032 HCWs (mean age 32.80 ± 10.75 years), that underwent occupational health surveillance between January 1st 2017 and March 31th 2018. The HCWs were also screened for measles, rubella, mumps using serological methods. 13% (405) was seronegative for mumps, especially among HCWs between 18 and 36 years. We calculated the cost-effectiveness of two-doses and three-doses MMR vaccination. The cost of vaccination without screening was significantly more expensive (cost difference: 99 712 € and 184 996 €) both in case of two-dose and three-dose MMR vaccination respectively. Our study suggests that, in HCWs, the assessment of the mumps antibody titer before vaccination may be a useful complement to vaccination itself, because it is more accurate and cost-effective than direct immunization of unvaccinated subjects.
Project description:Hepatitis B vaccine has been available worldwide since the mid-1980s. This vaccine was evaluated in a clinical trial in Thailand, conducted on subjects born to hepatitis B surface antigen positive and hepatitis B e-antigen positive mothers and vaccinated according to a 4-dose schedule at 0, 1, 2 and 12 mo of age and a single dose of hepatitis B immunoglobulin concomitantly at birth. All enrolled subjects seroconverted and were followed for 20 y to assess the persistence of antibody to the hepatitis B surface antigen (anti-HBs) (NCT00240539). At year 20, 64% of subjects had anti-HBs antibody concentrations?10 milli-international units per milli liter (mIU/ml) and 92% of subjects had detectable levels (?3.3 mIU/ml) of anti-HBs antibodies. At year 20, subjects with anti-HBs antibody titer<100 mIU/ml were offered an additional dose of hepatitis B virus (HBV) vaccine to assess immune memory (NCT00657657). Anamnestic response to the challenge dose was observed in 96.6% of subjects with an 82-fold (13.2 to 1082.4 mIU/ml) increase in anti-HBs antibody geometric mean concentrations. This study confirms the long-term immunogenicity of the 4-dose regimen of the HBV vaccine eliciting long-term persistence of antibodies and immune memory against hepatitis B for up to at least 20 y after vaccination.
Project description:BACKGROUND:HBV vaccine is known to offer protection against transmission of HBV infection. Health care workers are mandated to have this vaccination as part of their occupational health safety measures. Post vaccination response data for HCWs in our setting is not available. This study therefore aimed to evaluate the anti-HBs titre levels after Hepatitis B vaccination among HCWs from selected heath facilities in the Cape Coast Metropolis, Ghana. METHODS:A multicenter (3 selected sites) analytical cross-sectional study involving 711 HCWs was conducted. Five (5mls) of blood samples were collected from each study participant and the serum used for HBV immunological profile testing anti-HBs quantification by ELISA test (Fortress Diagnostics Limited, Northern Ireland, United Kingdom). Data analyses were performed using Stata version 14.0 software (STATA Corp, Texas USA). RESULTS:The median age of participants was 29 years (IQR = 26-35 years). Majority (80.9%, n = 575) took their vaccination from Government health facilities compared with 19.1% (n = 136) from private vaccination sources. A total of 7 (3 males and 4 females) were found to be HBsAg positive giving prevalence of 1%. In all, 8.2% (n = 58) of the HCWs had anti-HBs titre levels <10IU/ml giving a sero-protection rate of 91.8%. HCWs who received 3 doses of HBV vaccine were more likely to be sero-protected as compared to those who received only one dose in multivariate analysis (aOR = 3.39, 95%CI: 1.08-10.67), p<0.037). Gender, cigarette smoking and alcohol consumption were not found to be associated with sero-protection. CONCLUSION:There is a high HBV vaccine efficacy among HCWs in the Cape Coast Metropolis of Ghana with higher prevalence of anti-HBs titre level associated with full vaccine dose adherence. Post vaccination antibody titre determination could be an integral part of HBV vaccination protocol for HCWs in Ghana.
Project description:Health care workers (HCWs) are frequently exposed to hepatitis B virus (HBV) infection. The efficacy and safety of immunization with the hepatitis B (HB) vaccine are well recognized, but the durability of immunity and need for booster doses in those with secondary vaccine response failure remains controversial.This was a retrospective cohort study performed at Osaka University Hospital, Japan. We examined antibodies against HB surface antigen (anti-HBs) titers annually after immunization for previously non-immunized HCWs. Primary responders were categorized by their sero-positive durations as short responders (those whose anti-HBs titers declined to negative range within 3 years), and long responders (those who retained positive anti-HBs levels for 3 years and more). We re-immunized short responders with either single or 3-dose boosters, the long responders with a single booster when their titers dropped below protective levels, and examined their sero-protection rates over time thereafter.From 2001 to 2012, data of 264 HCWs with a median age of 25.3 were collected. The rate of anti-HBs positivity after primary vaccination were 93.0% after three doses (n = 229), 54.5% after two doses (n = 11), and 4.2% after a single dose (n = 24). Of 213 primary responders, the anti-HBs levels of 95 participants (44.6%) fell below the protective levels, including 46 short responders and 49 long responders. HCWs with higher initial anti-HBs titers after primary vaccination had significantly longer durations of sero-positivity. For short responders, 3-dose booster vaccination induced a longer duration of anti-HBs positivity compared to a single-dose booster, whereas for long responders, a single-dose booster alone could induce prolonged anti-HBs positivity.Our preliminary data suggested that it may be useful to differentiate HB vaccine responders based on their primary response durations to maintain protective levels of anti-HBs efficiently. A randomized, prospective, large-scale study is warranted to support our findings.
Project description:Follow-up studies of recipients of hepatitis B vaccine from endemic areas have reported loss of antibody to hepatitis B surface antigen (anti-HBs) in a high proportion of persons vaccinated at birth. In contrast, the long-term durability of antibody in persons vaccinated as adults in nonendemic areas is not well defined. We aimed to assess the durability of anti-HBs among healthcare workers (HCWs) vaccinated as adults and response to a booster among those without protective levels of antibody.Adult HCWs aged 18-60 at the time of initial vaccination were recruited. All were tested for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), and anti-HBs level. HCWs with anti-HBs <12 mIU/mL were offered a booster and levels were measured 1, 7, and 21 days afterward.Anti-HBs levels were <12 mIU/mL in 9 of 50 (18%), 13 of 50 (26%), and 14 of 59 (24%) HCWs 10-15, 16-20, and >20 years postvaccination, respectively, (P = ns). Four HCWs were anti-HBc positive; none had HBsAg. By logistic regression, older age at vaccination was the only predictor of inadequate anti-HBs level (P = .0005). Thirty-four of 36 subjects with inadequate anti-HBs levels received a booster and 32 (94%) developed levels >12 mIU/mL within 3 weeks.Anti-HBs levels decrease after 10-31 years and fall below a level considered protective in approximately 25% of cases. The rapid and robust response to a booster vaccine suggests a long-lasting amnestic response. Hepatitis B vaccination provides long-term protection against hepatitis B and booster vaccination does not appear to be necessary in HCWs. Clinical Trials Registration. NCT01182311.
Project description:No immunogenicity data has been reported after a single dose of the quadrivalent HPV vaccine (qHPV-Gardasil®) and no data are available on co-administration of this vaccine with the HAV/HBV vaccine (Twinrix-Junior®). Two pre-licensure studies reported similar anti-HPV but lower anti-HBs titers when co-administering HPV and HBV vaccines.To assess the immunogenicity of the qHPV and HAV/HBV vaccine when co-administered (Group-Co-adm) or given one month apart (Group-Sep) and to measure the persistence of HPV antibodies three years post-second dose of qHPV vaccine in both study groups.416 9-10 year-old girls were enrolled. Vaccination schedule was 0-6 months. Anti-HAV and anti-HBs were measured in all subjects 6 months post-first dose and 1 month post-second dose. Anti-HPV were measured 6 months post-first dose in Group-Co-adm and in all subjects 1 and 36 months post-second dose.Six months post-first dose: 100% of subjects had detectable anti-HAV and 56% and 73% had detectable anti-HBs in Group-Co-Adm and Group-Sep, respectively. In Group-Co-adm 94, 100, 99 and 96% had detectable antibodies to HPV 6, 11, 16 and 18, respectively. One month post-second dose of qHPV and HAV/HBV vaccine, in both study groups 99.5-100% of subjects had an anti-HAV titer ? 20IU/L, 97.5-97.6% an anti-HBs level ? 10IU/L, and 100% had an anti-HPV titer ? 3LU. Thirty-six months post-second dose of qHPV all but four subjects (99%) had antibodies to HPV18 and 100% had antibodies to HPV6, 11 and 16. The great majority (97-100%) had an anti-HPV titer ? 3 LU. Post-second dose administration of qHPV and HAV/HBV, no meaningful difference was observed in the immune response in the two study groups to any component of vaccines.The results indicate that qHPV and HAV/HBV can be given during the same vaccination session. Two doses of of qHPV and HAV/HBV vaccines induce a strong immune response. Three years post-second dose of qHPV, the great majority of subjects had antibodies to HPV types included in the vaccine. A two-dose schedule for pre-adolescents might be a reasonable alternative to the currently approved three-dose schedules.
Project description:Objective Since healthcare providers face an increased risk of hepatitis B virus (HBV) infection because of their work, vaccination plays a critical role in preventing HBV transmission. However, the duration for which acquired HBV surface antibodies (anti-HBs) persist remains unknown. To evaluate the primary immunologic response to HBV vaccination and its persistence in healthy Japanese adolescents. Methods In total, 690 young adults underwent HBV vaccination with a three-dose schedule. The primary response was determined by the anti-HBs titers at 1-2 months after the final dosage. Subjects with anti-HBs titers of <10, 10-100, and >100 mIU/mL were classified as "non-responders," "low-responders," and "sufficient responders," respectively. Anti-HB titers were re-measured at 1 or 2 years after vaccination. Results First, 95.8% and 72.8% of the subjects had anti-HBs titers of >10 and >100 mIU/mL, respectively, as a primary response. The anti-HBs titers measured at 1 and 2 years after vaccination were significantly correlated with those of the primary response (1 year: r=0.893, p<0.0001; 2 years: r=0.902, p<0.001). Most subjects with a titer of >100 mIU/mL at the primary response maintained an anti-HBs titer of >10 mIU/mL [1 year after vaccination, 208/209 (99.5%); 2 years after vaccination, 72/81 (90.1%)]. However, in subjects with a primary response of 10-100 mIU/mL the anti-HBs titer frequently declined; 17/38 (44.7%) and 9/10 (90.0%) subjects had a titer of <10 mIU/mL at 1 and 2 years, respectively. Conclusion The primary response was associated with the anti-HBs titers at 1 and 2 years after vaccination, and the anti-HBs titers of 54.2% of the low responders were not maintained for 2 years, even if they were vaccinated as healthy young adults.
Project description:Protection against hepatitis B disease relies on either protective serum antibodies or on the ability of the immune system to mount an anamnestic response when confronted with the hepatitis B virus (HBV). This open multicenter study (EUDRACT: 2010-022538-10) measured antibodies to HBV surface antigen (anti-HBs) in 7-8-year-old children who had received 4 doses of hexavalent diphtheria-tetanus-acellular pertussis-HBV-inactivated poliovirus-Hemophilus influenzae type b conjugate vaccine (DTPa-HBV-IPV/Hib: Infanrix™ hexa; GlaxoSmithKline Vaccines) in the first 2 years of life through routine vaccine services in Germany. The ability of these children to mount an anamnestic response to a challenge dose of monovalent HBV vaccine (Engerix™ B Kinder; GlaxoSmithKline Vaccines) was also assessed. Before the challenge dose, 78.5% of children had anti-HBs levels ?6.2 mIU/mL (seropositive) and 72.2% had anti-HBs levels ?10 mIU/mL (seroprotected). Post-challenge, 98.9% had anti-HBs levels ?10 mIU/mL and 95.8% had anti-HBs ?100 mIU/mL. An anamnestic response to the challenge was observed in 96.6% of all subjects. The challenge dose was well tolerated, with a reactogenicity and safety profile consistent with published data. DTPa-HBV-IPV/Hib induces long-lasting immune memory to HBV that appears very similar to that induced by monovalent HBV vaccines. Protection against hepatitis B may be conferred through immune memory in subjects who responded to primary vaccination, even when they subsequently lose detectable levels of circulating anti-HBs antibodies.
Project description:This study assessed antibody persistence and immune memory to hepatitis B vaccine 20 y after priming with a recombinant hepatitis B virus (HBV) vaccine during infancy. Infants were vaccinated according to a 0, 1, 6 mo schedule with or without simultaneous administration of hepatitis B immunoglobulin (HBIg). Half of the subjects enrolled received an interim booster dose at year 5 (boosted) group, whereas the other half of the subjects enrolled did not (unboosted group). Antibody persistence was assessed until year 20. Immune memory was assessed by administration of a final HBV vaccine challenge dose at year 20 in a second study. At year 20, anti-HBs antibody concentration ? 10 mIU/ml rates and GMCs were higher among subjects in the boosted group (84.2% [16/19]; 95%CI: 60.4-96.6) when compared with those in the unboosted group [44.0% (11/25)]; 95% CI: 24.4-65.1). After the HBV vaccine challenge dose at year 20, anti-HBs anamnestic response for subjects in the unboosted and boosted groups was observed in 93.1% (95% CI: 77.2-99.2) and 100% (95% CI: 76.8-100) of subjects, respectively. The mean anti-HBs antibody concentration (GMC) was 562.0 mIU/ml (292.5-1079.7 mIU/ml) post administration of the challenge dose; this is a 28.5 fold increase from the pre- to post-challenge dose administration at year 20. This study demonstrates persistence of anti-HBs antibodies and presence of immune memory following hepatitis B vaccination for up to at least 20 y in Thailand. Immune memory was demonstrated for virtually all subjects, regardless whether they received they had received the additional HBV dose or not. The challenge dose at year 20 was well tolerated and a robust response was demonstrated. ClinicalTrials.gov Identifier: NCT00240526, NCT00774995.
Project description:The response to the HBV vaccine in HIV-infected patients is deficient. Our aim was to analyze whether a suppressive combined antiretroviral treatment (cART) containing maraviroc (MVC-cART) was associated with a better response to HBV vaccine. Fifty-seven patients on suppressor cART were administered the HBV vaccine. The final response, the early response, and the maintenance of the response were assessed. An anti-HBs titer of >10 mIU/ml was considered a positive response. A subgroup of subjects was simultaneously vaccinated against hepatitis A virus (HAV). Lineal regression analyses were performed to determine demographic, clinical, and immunological factors associated with the anti-HBs titer. Vaccine response was achieved in 90% of the subjects. After 1 year, 81% maintained protective titers. Only simultaneous HAV vaccination was independently associated with the magnitude of the response in anti-HBs titers, with a P value of 0.045 and a regression coefficient (B) [95% confident interval (CI)] of 236 [5 to 468]. In subjects ?50 years old (n = 42), MVC-cART was independently associated with the magnitude of the response (P = 0.009; B [95% CI], 297 [79 to 516]) together with previous vaccination and simultaneous HAV vaccination. High rates of HBV vaccine response can be achieved by revaccination, simultaneous HAV vaccination, and administration of cARTs including MVC. MVC may be considered for future vaccination protocols in patients on suppressive cART.