Long-term Antibody Persistence Research Articles

Long-term persistence of anti-rods and rings antibodies in patients with chronic hepatitis C after antiviral treatment.

Anti-rods and rings (anti-RR) antibodies are related to hepatitis C virus (HCV) in patients treated with pegylated interferon (PEG-IFN) and ribavirin (RBV). Only RBV induces rods/rings structures in vitro; but in vivo, the antibody appearance is related to the combination of these drugs, because data about patients using just one of these drugs alone is missing. Some studies suggest disappearance of these antibodies over time. The aim of this study was to describe the occurrence of anti-RR in patients with chronic hepatitis C treatment-naïve or previously PEG-IFN/RBV-experienced, evaluating the persistence of anti-RR antibodies long after PEG-IFN/RBV treatment. From 2016 to 2017, 70 HCV-infected patients were screened for anti-RR using indirect immunofluorescence. Demographic and clinical data about previous treatments against HCV were assessed. Thirty-four patients (49%) had been previously treated with PEG-IFN/RBV and the average time since they had received the last antiviral treatment was 85.4months. Anti-RR seropositivity was detected in 16 patients (23%), and all of these had used PEG-IFN/RBV (corresponding to 47% of experienced patients). Previous antiviral treatment and previous exposure time to RBV were associated with anti-RR positivity. Median time elapsed since last treatment was similar between anti-RR-positive and anti-RR-negative patients. Anti-RR seropositivity was not observed in treatment-naïve patients, but was detected in almost half of patients previously treated with PEG-IFN and RBV, even after a long period without exposure to these drugs. This antibody was related to extended prior exposure to ribavirin.

Long-term antibody persistence against hepatitis B in adolescents 14–15-years of age vaccinated with 4 doses of hexavalent DTPa-HBV-IPV/Hib vaccine in infancy

ABSTRACTWe evaluated antibody persistence against hepatitis B virus (HBV) in adolescents previously vaccinated with a hexavalent diphtheria-tetanus-acellular pertussis-HBV-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine (DTPa-HBV-IPV/Hib), as part of the national newborn immunization program in Germany. We also assessed the anamnestic response to a challenge dose of a monovalent HBV vaccine. In this phase 4, open-label, non-randomized study (NCT02798952), 302 adolescents aged 14–15 years, primed in their first 2 years of life with 4 DTPa-HBV-IPV/Hib doses, received one challenge dose of monovalent HBV vaccine. Blood samples were taken before and one month post-vaccination and used to determine antibody levels against hepatitis B surface antigen (HBs). Reactogenicity and safety were also assessed post-challenge dose. Pre-challenge dose, 53.7% of 268 participants included in the according-to-protocol cohort for immunogenicity had anti-HBs antibody concentrations ≥10 mIU/mL (seroprotection cut-off) and 16.8% had anti-HBs antibody concentrations ≥100 mIU/mL. One month post-challenge dose, 93.3% of adolescents had anti-HBs antibody concentrations ≥10 mIU/mL and 87.3% had antibody concentrations ≥100 mIU/mL. An anamnestic response was mounted in 92.5% of adolescents. Injection site pain (in 33.6% of participants) and fatigue (30.2%) were the most frequently reported solicited local and general symptoms, respectively. Six of the 55 unsolicited adverse events reported were considered vaccination-related. Two vaccination-unrelated serious adverse events were reported during the study. Long-term antibody persistence against hepatitis B was observed in 14–15 years old adolescents previously primed in infancy with DTPa-HBV-IPV/Hib. A challenge dose of monovalent HBV vaccine induced strong anamnestic response, with no safety concerns.

Antibody Persistence up to 3 Years After Primary Immunization With Inactivated Japanese Encephalitis Vaccine IXIARO in Philippine Children and Effect of a Booster Dose.

An inactivated Vero cell culture derived Japanese encephalitis virus vaccine (IXIARO) requires a booster dose 1 year after primary schedule for long-term antibody persistence in adults. The aim of this study is to evaluate immunogenicity and safety of a booster dose in children 2 months to <18 years of age. This is a randomized, controlled open-label study in the Philippines. Three hundred children vaccinated with IXIARO in a previous trial were randomized 1:1 to receive either no booster or a booster 12 months after initiation of the primary series. Neutralizing antibody titers were assessed before and after the booster and up to 3 years after primary series. Safety endpoints included the rate of subjects with solicited adverse events (AEs), unsolicited AEs and serious AEs within 1 month after the booster. Geometric mean titer declined by 1 year after the primary series, but titers remained above the established protective threshold in 85%-100% of children depending on age group. The booster led to a pronounced increase in geometric mean titer and 100% seroprotection rate in all age groups. The booster was well tolerated, with AE rates lower compared with the primary series. Most AEs were mild. A booster dose of IXIARO administered 12 months after the primary immunization was well tolerated and highly immunogenic.

A Ten Year Immunopersistence Study of Hepatitis E Antibodies in Rural Bangladesh.

Hepatitis E virus (HEV) is a major cause of acute viral hepatitis in Southeast Asia. Several studies have suggested that antibody persistence after HEV infection may be transient, possibly increasing the risk of reinfection and contributing to the frequency of outbreaks in HEV-endemic regions. The specific conditions under which antibodies to HEV are lost, or “seroreversion” occurs, are poorly understood. Here, 100 participants from population-based studies in rural Bangladesh were revisited in 2015, 10 years after a documented HEV infection, to examine long-term antibody persistence. Twenty percent (95% confidence interval: 12.0, 28.0) of the participants no longer had detectable antibodies at follow-up, suggesting that antibodies generally persist for at least a decade after infection in rural Bangladesh. Persons who were seronegative at follow-up were generally younger at infection than those who remained positive (14.4 years vs. 33.6 years; P < 0.0001). This age-dependent antibody loss could partially explain cross-sectional seroprevalence data from Southeast Asia, where children have reportedly low antibody prevalence. The results of this study provide new insight into the immunological persistence of HEV infection in a micronutrient-deficient rural population of South Asia, highlighting the importance of age at infection in the ability to produce long-lasting antibodies against HEV.

Persistence of hepatitis B immune memory until 9–10 years of age following hepatitis B vaccination at birth and DTaP-IPV-HB-PRP∼T vaccination at 2, 4 and 6 months

ABSTRACTObjective: To evaluate the long-term persistence of anti-hepatitis B surface (HBs) antibodies and the response to a HB challenge re-vaccination in children who had received a primary series of DTaP-IPV-HB-PRP∼T (Hexaxim™) or DTaP-IPV-HB/PRP∼T (Infanrix hexa™).Methods: Two cohorts of participants who had previously received HB vaccine at birth followed by either DTaP-IPV-HB-PRP∼T or DTaP-IPV-HB/PRP∼T co-administered with PCV7 at 2, 4, 6 months of age in a randomized, Phase III, observer-blind study in Thailand, were followed up for anti-HBs antibodies (geometric mean concentrations [GMCs] and seroprotection [SP] rate [% of participants with a titer ≥10 mIU/mL]) at 12–18 months of age and 9–10 years of age. A monovalent HB challenge re-vaccination was administered at 9–10 years of age and the anamnestic response was evaluated.Results: Anti-HBs GMCs and SP rates in the DTaP-IPV-HB-PRP∼T and DTaP-IPV-HB/PRP∼T groups were high and similar post-primary vaccination series (2477 mIU/mL and 99.5% and 2442 mIU/mL and 99.5%, respectively) and declined to a similar extent in each group at 12–18 months (154.5 mIU/mL and 90.8% and 162.3 mIU/mL and 96.5%, respectively). Antibody levels further declined at 9–10 years of age (13.3 mIU/mL and 49.3% and 8.0 mIU/mL and 42.9%) and a strong anamnestic response occurred in each group post-HB challenge re-vaccination (92.8% and 98.7%, respectively).Conclusion: The kinetics of long-term anti-HBs antibody persistence were similar following a primary series of DTaP-IPV-HB-PRP∼T or DTaP-IPV-HB/PRP∼T. The response to a subsequent HB challenge re-vaccination was strong and similar in each group, demonstrating persisting immune memory.

Second five-year follow-up after a booster vaccination against tick-borne encephalitis following different primary vaccination schedules demonstrates at least 10 years antibody persistence

BackgroundTick borne encephalitis (TBE) endemic zones are expanding. We previously evaluated long term persistence of antibody 5 years after the first booster immunization following different primary immunization schedules with the polygeline-free inactivated TBE vaccine (TBEvac) in adults and adolescents. Here, we report anti-TBE virus (TBEV) antibody persistence from 6 to 10 years post-booster administration. MethodsThis was a phase IV, open-label, single-center, second extension study (NCT01562444), conducted in Czechia. Healthy adults and adolescents ≥12 years who had received 3 different primary vaccination schedules (rapid, conventional and accelerated conventional) in the parent study and a booster dose before (12–18 months post-primary series completion) or at the beginning (3 years post-primary series completion) of the first extension study were screened and enrolled in this study. Blood samples were collected yearly and anti-TBEV antibody response was evaluated by neutralizing test (NT) antibody assays. Analysis was performed overall and per age strata: 15–49 years, ≥50 years, and ≥60 years. ResultsOf 206 screened individuals, 191 completed the study. Overall, 90–100% of participants in the all-screened set and ≥97% in the per-protocol set had the clinically meaningful threshold of protection (NT titers ≥10) across all timepoints, regardless of the primary vaccination schedule. Overall, antibody geometric mean titers (GMTs) varied from 134 to 343 in the all-screened set. Older age groups showed overall lower GMTs, although GMTs remained higher than NT titers ≥10 up to year 10 in all groups. ConclusionThis study showed long-term persistence of anti-TBEV NT antibodies for up to 10 years after the first booster dose of TBEvac in all age groups, regardless of the primary vaccination schedule.

Serological survey of mumps antibodies in adults in the Czech Republic and the need for changes to the vaccination strategy

ABSTRACTMumps outbreaks, especially in adolescents and young adults, have been reported in the Czech Republic. The aim of the presented study was to determine the seroprevalence of specific IgG antibodies against mumps in the adult population of the Czech Republic. The study was designed as a multicenter serological survey of adults aged 18 years and over. Specific IgG antibodies against mumps were detected in blood samples using an enzyme-linked immunosorbent assay (ELISA). A total of 1,911 serum samples were examined. The overall seropositivity reached 55.3%. In individual age groups, the highest seropositivity 63% (63.5–65.2%) was recorded in adults aged 40 years and over; the lowest seropositivity was found in adults aged 18–29 years (27.4%). The difference in seropositivity rate between the 18–29 years age group and the 40 years and over age groups was statistically significant (p < 0.001). Only the 18–29 years age group included both vaccinated and unvaccinated (born in the pre-vaccine era) individuals. In vaccinated individuals, seropositivity was reported in only 19.1% of persons; in unvaccinated individuals, seropositivity reached 48.2%. Our results demonstrate the long-term persistence of antibodies following natural infection and the decrease in seropositivity that occurs after vaccination over time. This immunity waning may account for the higher susceptibility of adolescents and young adults to mumps. Therefore, the current vaccination program in the Czech Republic could be considered as less effective. It will be modified with the shifting of the second dose of vaccine from two years of age to the preschool age.

Antibody persistence and booster responses 24–36 months after different 4CMenB vaccination schedules in infants and children: A randomised trial

ObjectivesThis phase IIIb, open-label, multicentre, extension study (NCT01894919) evaluated long-term antibody persistence and booster responses in participants who received a reduced 2 + 1 or licensed 3 + 1 meningococcal serogroup B vaccine (4CMenB)-schedule (infants), or 2-dose catch-up schedule (2–10-year-olds) in parent study NCT01339923. Materials and methodsChildren aged 35 months to 12 years (N = 851) were enrolled. Follow-on participants (N = 646) were randomised 2:1 to vaccination and non-vaccination subsets; vaccination subsets received an additional 4CMenB dose. Newly enrolled vaccine-naïve participants (N = 205) received 2 catch-up doses, 1 month apart (accelerated schedule). Antibody levels were determined using human serum bactericidal assay (hSBA) against MenB indicator strains for fHbp, NadA, PorA and NHBA. Safety was also evaluated. ResultsAntibody levels declined across follow-on groups at 24–36 months versus 1 month post-vaccination. Antibody persistence and booster responses were similar between infants receiving the reduced or licensed 4CMenB-schedule. An additional dose in follow-on participants induced higher hSBA titres than a first dose in vaccine-naïve children. Two catch-up doses in vaccine-naïve participants induced robust antibody responses. No safety concerns were identified. ConclusionAntibody persistence, booster responses, and safety profiles were similar with either 2 + 1 or 3 + 1 vaccination schedules. The accelerated schedule in vaccine-naïve children induced robust antibody responses.

Long-term study (2005-2010) on the vaccination with BoHV-1 glycoprotein E-deleted marker vaccine in selected two dairy herds in Turkey.

A follow-up study from 2005 to 2010 was carried out in two herds where eradication programme for the bovine herpes virus-1 (BoHV-1) infection depends on the vaccination with inactivated glycoprotein E-deleted vaccine that was started in 2001 following the vaccination with inactivated conventional vaccine between 1999 and 2001. For serological screening, a total of 12,976 sera sampled over several sampling times approximately 6months of interval during 5years (2005-2010) were tested for glycoprotein E (gE)- and glycoprotein B-specific antibodies using ELISA. According to the serological evidence, the long-term persistence of BoHV-1 antibodies, success of marker vaccine, first vaccination time of the calves in herds regularly vaccinated, etc. were discussed in this paper. In conclusion, the vaccination programme using gE (-) marker vaccines, with making efforts to prevent the other factors about transmission of infection, was suggested for the eradication of BoHV-1 infection in Turkey as many EU countries. This is the first report on the BoHV-1 eradication programme in some dairy cattle in Turkey.

Seropersistence of TBE virus antibodies 10 years after first booster vaccination and response to a second booster vaccination with FSME-IMMUN 0.5 mL in adults

Tick-borne encephalitis (TBE) is a viral disease that can have a severe acute clinical course and considerable long-term morbidity. As there is no causal treatment currently available for TBE, vaccination is the only way to combat the disease in endemic areas. The studies presented here were conducted to obtain prospective long-term TBE serum antibody persistence data of subjects up to 10years after the first booster with FSME-IMMUN.This report presents the results of 2 follow-up studies in the same study population of 315 healthy adults. Blood was drawn to assess the seropersistence of TBE virus antibodies yearly, from 2–5 and 7–10years after the first booster vaccination with FSME-IMMUN administered during a previous study. The timing of the second booster vaccination was dependent on the level of serum TBE antibodies observed during yearly follow-up serology observations.The current follow up showed that adult recipients were 84.9% seropositive 10years after a 3 dose primary series and the first booster vaccination of FSME-IMMUN. Seropositivity rates were even higher (88.6%) in subjects below 50years of age.ClinicalTrials.gov Identifier: NCT00503529.ClinicalTrials.gov Identifier: NCT01582698.

Memory B cell response to a PCV-13 booster in 3.5 year old children primed with either PCV-7 or PCV-13

Pneumococcal protein-polysaccharide conjugate vaccines provide direct protection against Streptococcus pneumoniae through the induction of persistent anti-polysaccharide antibodies, and by priming for a rapid secondary antibody response. Memory B cells (BMEM) generated during an initial immune response are responsible for both the more rapid and quantitatively greater secondary antibody response and are also thought to contribute to the ongoing production of plasma cells providing long-term antibody persistence. We recruited 3.5-year-old children who had participated in a previous clinical trial comparing infant immunization with either a 7-valent (PCV-7) or a 13-valent pneumococcal conjugate vaccine (PCV-13) to investigate whether prior priming with pneumococcal antigens influences BMEM responses. Blood was taken before and 1month after a PCV-13 booster. BMEM were quantified using a cultured ELISpot assay for pneumococcal serotypes 1, 3, 4, 14, 19A, 23F, and with diphtheria and tetanus toxoid as controls, and then correlated with serotype-specific IgG concentrations and opsonophagocytic activity (OPA) titers. In total, blood samples from 62 participants were available for analysis. Serotype-specific BMEM frequencies were generally low at baseline (before boost) although for serotypes 14 and 3, they were significantly higher in children primed with PCV-13 than PCV-7 primed children. Following the PCV-13 booster, BMEM frequencies increased and were not different between the groups for all serotypes. A strong inverse correlation was found between antibody concentrations and OPA titers at baseline and BMEM following booster vaccination for serotype 3 but not for other serotypes suggesting that, for this serotype, pre-existing serotype-specific antibodies may inhibit BMEM formation in response to vaccination.Clinicaltrials.gov registration number: NCT01095471.

Long-term persistence of protective antibodies in Dutch adolescents following a meningococcal serogroup C tetanus booster vaccination

IntroductionDue to waning immunity, infant vaccination with meningococcal serogroup C conjugated (MenCC) vaccines is insufficient to maintain long-term individual protection. Adolescent booster vaccination is thought to offer direct protection against invasive meningococcal disease (IMD) but also to reduce meningococcal carriage and transmission and in this way establish herd protection in the population. Previously, we studied antibody levels after adolescent MenCC booster vaccination. In the present study, the adolescent vaccinees were revisited after three years to determine antibody persistence and to predict long-term protection. MethodsMeningococcal serogroup C tetanus toxoid conjugated (MenC-TT) vaccine was administered to 10-, 12- and 15-year old participants who had been primed nine years earlier with a single dose of MenC-TT vaccine. Blood samples were collected before, 1month, 1year and 3years after the adolescent booster vaccination. Functional antibody levels were measured with serum bactericidal assay using rabbit complement (rSBA). Meningococcal serogroup C polysaccharide and tetanus toxoid specific antibody levels were measured using fluorescent-bead-based multiplex immunoassay. Long-term protection was estimated using longitudinal multilevel antibody decay modeling. ResultsOf the original 268 participants, 201 (75%) were revisited after 3years. All participants still had an rSBA titer above the protective threshold of ⩾8 and 98% ⩾128. The 15-year-olds showed the highest antibody titers. Using a bi-exponential decay model, the median time to fall below the protection threshold (rSBA titer <8) was 16.3years, 45.9years and around 270years following the booster for the 10-, 12- and 15-year-olds, respectively. ConclusionsAfter a first steep decline in antibody levels in the first year after the booster, antibody levels slowly declined between one and three years post-booster. A routine MenC-TT booster vaccination for adolescents in the Netherlands will likely provide long-term individual protection and potentially reduce the risk of resurgence of MenC disease in the general population.

Antibody persistence and immunologic memory in children vaccinated with 4 doses of pneumococcal conjugate vaccines: Results from 2 long-term follow-up studies

ABSTRACTTo investigate long-term antibody persistence following the administration of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV), we present results of 2 follow-up studies assessing antibody persistence following 2 3+1 schedules up to 4 (NCT00624819 – Study A) and 5 years (NCT00891176 – Study B) post-booster vaccination. In Study A, antibody persistence was measured one, 2 and 4 years post-booster in children previously primed and boosted with PHiD-CV, or primed with the 7-valent pneumococcal conjugate vaccine (7vCRM) and boosted with either PHiD-CV or 7vCRM. In Study B, PHiD-CV was co-administered with meningococcal vaccines, and pneumococcal antibody persistence was measured 2, 3 and 5 years post-booster. An age-matched control group, unvaccinated against Streptococcus pneumoniae, was enrolled in Study A, allowing assessment of immunologic memory by administration of one dose of PHiD-CV to both primed (4 years post-booster) and unprimed 6-year-old children. Four years post-booster (Study A), antibody concentrations and opsonophagocytic activity (OPA) titers remained higher compared to the pre-booster timepoint, with no major differences between the 3 primed groups. Antibody persistence was also observed in Study B, with minimal differences between groups. The additional PHiD-CV dose administered 4 years post-booster in Study A elicited more robust immune responses in primed children than in unprimed children. Long-term serotype-specific antibody persistence and robust immunologic memory responses observed in these 2 studies suggest induction of long-term protection against pneumococcal disease after PHiD-CV vaccination.

Long-term antibody persistence study (3 years after last dose) of the 7-valent pneumococcal conjugate vaccine in young children in China

BackgroundIn a previous study, Chinese infants were vaccinated with 7-valent pneumococcal conjugate vaccine (PCV7) ⩾7days before routine diphtheria, tetanus, and acellular pertussis vaccine (DTaP); PCV7 administered concomitantly with DTaP (PCV7+DTaP); or DTaP alone. This study examined antibody persistence at a single time point 3years after the last vaccination. MethodsChildren who participated in the prior PCV7 study were eligible to participate. A single blood sample was drawn at enrollment. Immunoglobulin G (IgG) geometric mean concentrations (GMCs) specific to the PCV7 serotypes and percentages of subjects with IgG ⩾0.35μg/mL were compared for subjects receiving PCV7 versus PCV7+DTaP (concomitant) and for PCV7 or PCV7+DTaP (concomitant) versus DTaP alone. IgG concentrations at 3years after the last vaccination were also compared with those after the infant series and toddler dose. ResultsThree years after the last vaccination with PCV7 or PCV7+DTaP (concomitant), IgG GMCs for most PCV7 serotypes were lower than after the infant series or toddler dose but remained above prevaccination concentrations. IgG GMC were similar between the PCV7 and PCV7+DTaP (concomitant) groups for 5 out of 7 serotypes but serotypes 4 and 19F were significantly lower in the PCV7+DTaP (concomitant) recipients. Three years after the last vaccination, IgG GMCs were significantly higher for 6 of 7 PCV7 serotypes among those receiving PCV7 or PCV7+DTaP (concomitant) compared with recipients of DTaP alone. Among subjects receiving DTaP alone, serotype-specific antibody concentrations were significantly higher for all serotypes 3years after the last vaccination compared with after the infant series. ConclusionThree years after PCV7 vaccination, serotype-specific antibodies were lower than after the primary infant series but higher than prevaccination levels and higher among subjects who received PCV7 compared with those who did not. The immune response was comparable in children who received PCV7 with and without concomitant DTaP.Clinical Trial Registration: NCT01298544

Antibodies in acquired demyelinating disorders in children

The discovery that several demyelinating disorders in children may be associated with autoantibodies to astrocytes, myelin, and/or synaptic proteins has opened the possibility of their use as diagnostic and prognostic biomarkers. The identification of aquaporin 4 (AQP4) antibodies as specific diagnostic markers of neuromyelitis optica (NMO) led to an expansion of the clinical spectrum of this disorder to include patients with incomplete forms or with manifestations outside of the optic nerves and spinal cord. Recently, an international panel of experts proposed the use of the term NMO spectrum disorders (NMOSD) to encompass all of these phenotypes. Although rare in children, the early identification of AQP4 antibodies has important prognostic and therapeutic implications as their presence is highly predictive of relapses and accumulation of disability. More recently, antibodies to myelin oligodendrocyte glycoprotein (MOG) have been described in children and adults diagnosed with NMOSD and seronegative for AQP4 antibodies, as well as in children with other acquired demyelinating disorders. For example 60 % of children with acute demyelinating encephalomyelitis (ADEM) have MOG antibodies. Whether MOG antibodies are pathogenic or surrogate biomarkers of the disease is unclear but their identification is important for two reasons. First, patients with a first demyelinating event who are MOG antibody positive are unlikely to develop multiple sclerosis (MS); and second, the long-term persistence of MOG antibodies associates with recurrent non-MS demyelinating disorders such as NMOSD, recurrent optic neuritis or transverse myelitis, or multiphasic ADEM. Other antibodies, such as those targeting Kir 4.1 or the glycine receptor have also been described in association with pediatric MS and other demyelinating disorders but their clinical relevance, and existence, in the case of Kir 4.1, is still under investigation. The focus of this review will be the current data on the antibodies mentioned above, and the recent discovery that some children have both a demyelinating disorder and autoimmune encephalitis. The presence of antibodies against targets related to demyelinating disorders (AQP4 or MOG) and those related to autoimmune encephalitis (e.g., N-methyl-D-aspartate receptor), supports the concurrence of two autoimmune disorders in these patients.

Long-term persistence of anti-hantavirus antibodies in sera of patients undergoing hemorrhagic fever with renal syndrome and subjects vaccinated against the disease

Background China has the highest prevalence of hemorrhagic fever with renal syndrome (HFRS) and accounts for 90% of the total cases worldwide. However, the long-term persistence of anti-hantavirus antibodies in sera of patients with HFRS and subjects vaccinated against the disease remains unclear. The aim of the present study was to investigate the prevalence of anti-hantavirus IgG antibodies in sera of patients with prior HFRS, versus subjects vaccinated against the disease and controls in Shaanxi, China. Methods Six hundred individuals were included in this study. We quantified anti-hantavirus IgG antibodies in HFRS patients (n = 100), vaccinees (n = 200), controls from endemic regions (n = 200), and controls from non-endemic regions (n = 100) in China. Results The median optical density (OD) values (range) were 0.803 (0.008–1.813), 0.075 (0.004–1.565), 0.026 (0–1.179), and 0.015 (0.009–0.118) for HFRS patients, vaccinated subjects, endemic controls, and non-endemic controls, respectively. There was a strikingly significant difference between the HFRS group and each non-HFRS group (p < 0.001). The vaccinated subjects were also significantly different from the endemic controls. The time since the acute phase was correlated with the OD values of the HFRS patients. Conclusions Our study suggests that HFRS patients gain long-lasting protection and that vaccination may be an effective way to stimulate antibody production.

Safety and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (IMOJEV®) in children

ABSTRACTJE-CV (IMOJEV®, Sanofi Pasteur, France) is a live attenuated virus vaccine constructed by inserting coding sequences of the prM and E structural proteins of the Japanese encephalitis SA14-14-2 virus into the genome of yellow fever 17D virus. Primary immunization with JE-CV requires a single dose of the vaccine. This article reviews clinical trials of JE-CV in children aged up to 6 years conducted in countries across South-East Asia. Strong and persistent antibody responses were observed after single primary and booster doses, with 97% of children seroprotected up to five years after booster vaccination. Models of long-term antibody persistence predict a median duration of protection of approximately 30 years after a booster dose. The safety and reactogenicity profiles of JE-CV primary and booster doses are comparable to other widely used childhood vaccines.

Hepatitis B immune status in adolescents vaccinated during infancy: A retrospective cohort study from a pediatric practice in Germany

abstractIn Germany, vaccination of infants against hepatitis B is recommended since 1995. However, data on long-term immunity is sparse and the necessity of a booster dose remains uncertain. Aims of this study were to assess the long-term persistence of antibodies to the hepatitis B surface antigen (anti-HBs) after immunization during infancy and the effect of a subsequent hepatitis B booster vaccination during adolescence on anti-HBs levels. Patients from a private pediatric practice who had received a full vaccination course of hepatitis B as infants and who were quantitatively tested for anti-HBs during adolescence (pre-booster levels) were included. In those participants who received a hepatitis B booster, post-booster anti-HBs levels were measured. Univariate analyses were conducted to determine factors associated with pre- and post-booster anti-HBs levels, respectively. 106 participants (53% male) were included in the study. At an average of 13.7 y after primary vaccination, 14% of participants had an anti-HBs level of ≥100 IU/l, while 46% were at 10–99 IU/l and 40% had anti-HBs levels of <10 IU/l. In total, 34 received a booster vaccination. Of those, 97% (33/34) had post-booster anti-HBs levels ≥ 100 IU/l, which were independent from pre-booster levels. No other patient characteristics were associated with pre-booster or post-booster anti-HBs≥ 100 IU/l. Although almost half of study participants showed low anti-HBs levels at follow-up, robust responses to booster vaccination suggest that adolescents who received the full vaccination course during infancy are still protected against hepatitis B infection.

Schmallenberg virus antibody development and decline in a naturally infected dairy cattle herd in Germany, 2011–2014

In late 2011, the novel insect-transmitted orthobunyavirus Schmallenberg virus (SBV) emerged in Central Europe. Since that year, a dairy cattle herd kept in the German region in which the virus was initially detected was continuously monitored. In order to evaluate the development of the within-herd seroprevalence, but also to assess the long-term persistence of antibodies against SBV in individual animals, blood samples of all cows older than 24 months were taken yearly after the respective vector season and serologically analyzed. In December 2011, in 74% of the tested animals SBV-specific antibodies were detectable. Additional scattered seroconversions were observed between the 2011 and 2012 vector seasons, thereafter all seronegative animals remained negative. Until December 2014, the intra-herd seroprevalence decreased to 58%. A total of 122 cows infected presumable in autumn 2011 were sampled every year, 9 of them became seronegative until December 2014. Consequently, though SBV-specific antibodies were detected in about 90% of the monitored animals for more than three years, a lifelong antibody-based immunity is not expected in every animal. The loss of anti-SBV antibodies in individual animals combined with the missing infection of young stock results in a declining herd seroprevalence and increases the risk of a renewed virus circulation to a greater extent within the next years.

Long-term antibody persistence after vaccination with a 2-dose Havrix™ (inactivated hepatitis A vaccine): 20 years of observed data, and long-term model-based predictions

Antibody persistence in two cohorts of adults, who received inactivated hepatitis A (HAV) vaccine (1440El.U; Havrix™; GSK Vaccines) according to a 0–6 or 0–12 month schedule in 1992–1993, has been measured annually. After 20 years, >97% of the subjects in both studies were seropositive for anti-HAV antibodies. Geometric mean concentrations in the according-to-protocol cohorts were 312mIU/ml in 34/36 subjects vaccinated initially at 0–6 months (NCT00289757) and 317mIU/ml in 85/86 subjects vaccinated at 0–12 months (NCT00291876). Over the whole follow-up period, seven subjects (2+5, respectively) lost circulating anti-HAV antibodies but mounted a strong response after HAV booster administration (1440El.U). Mathematical modelling, which was applied to assess true persistence at Year 20 (accounting for drop-outs and missing data), and to predict longer-term persistence confirmed previous estimates that seropositive anti-HAV levels would persist in ≥95% vaccinees at Year 30 and ≥90% at Year 40.ClinicalTrials.Gov number: NCT00289757/NCT00291876