Characteristics of immune memory 10–15 years after primary hepatitis B vaccination

Background and aimsThe definition of immune memory after hepatitis B vaccination is still under debate. Therefore, we analysed hepatitis B surface antigen (HBsAg)-specific memory in more detail by investigating the kinetics of humoral and cellular responses after hepatitis B booster vaccination.MethodsThe anti-HBs kinetics of 23 individuals with anti-HBs titres below 10 IU/l, who had been vaccinated 10–15 years ago, was monitored at day 0, 3, 7, 14 and 28 after booster vaccination. HBsAg-specific IFNγ- and IL5-secreting cells in enriched CD4⁺ fraction were measured at day 0, 7 and 28 post-booster by enzyme-linked immunospot assay (ELISpot).Results22 of 23 subjects showed similar anti-HBs kinetic curves, including 3 of 4 subjects who did not reach anti-HBs titres of 10 IU/l. The steep anti-HBs increase started between day 3 and 7 and peaked around day 14. A plateau or only minimal changes were visible between day 14 and 28. 17.4% of subjects showed pre-booster cellular responses, and this rate had increased to 47.8% and 56.5% after 7 and 28 days, respectively. The kinetic patterns of T cell responses differed considerably among subjects. A dominance of Th2 responses (IL5 secretion) over Th1 responses (IFNγ secretion) could be observed.ConclusionsThe presence of B cell memory could be shown by a typical anamnestic anti-HBs response curve after a booster dose in all but one individual. In contrast, T cell responses to booster vaccination, which occurred in approximately 50% of participants, were rather heterogeneous.     

Hepatitis B infection control in Colombian Amazon after 15 years of hepatitis B vaccination. Effectiveness of birth dose and current prevalence

BackgroundHepatitis B virus (HBV) infection is highly endemic in the Colombian Amazon basin. In Colombia, the universal hepatitis B vaccination in that area has been active since 1993. The program targets children aged under five years. Newborns receive at least three doses, and in 2001, HBV vaccine birth dose was included. This study aimed to evaluate the advances on HBV control in the Colombian Amazon.MethodsA population-based cross-sectional study was conducted in children less than 11 years old in rural areas of the Colombian Amazon, in order to assess the current levels of HBV prevalence and evaluate the effectiveness of HBV vaccination. Participants were selected from villages scattered along the Amazon, Putumayo and Loretoyaco Rivers. Blood samples were taken from children. All the samples were examined for surface antigen (HBsAg) and IgG antibodies against core antigen (AntiHBc) of HBV. Data on HBV vaccination status and other risk factors were also collected.ResultsBlood samples from 1275 children were included in the study. The positivity for IgG AntiHBC and HBsAg was 3.8% and 0.5%, respectively. It was observed that receiving a dose of HBV vaccine within 48 h after birth decreased the risk of HBV infection and carriage by 95%. Being born to an AntiHBc positive mother increased 8 times the risk of HBV infection (OR  =  7.8 CI 95% 3.3–10.2) and 7 times the risk of HBsAg carriage (OR  =  6.6 CI 95% 2.1–10.1).ConclusionThe prevalence of HBV infection and HBsAg carriage continues to decrease among children living in the Colombian Amazon. The high protective effectiveness of an HBV birth does suggest that perinatal transmission is important in endemic areas of Latin America, an aspect that has not been fully studied in the region.     

Observational study of vaccine effectiveness 20 years after the introduction of universal hepatitis B vaccination in Tunisia

ObjectivesThe objectives of this study were to estimate the national prevalence of hepatitis B infection in Tunisia using data from a nationwide survey, to compare results with those obtained in 1996 survey and to evaluate the impact of vaccination twenty years after its introduction.MethodsA National household-based cross sectional and serological survey was undertaken in 2015 from randomly selected districts using two-stage sampling. Data collection was performed using standardized and pretested questionnaires and collected blood samples were tested for markers of hepatitis B virus infection.ResultsNational point prevalence of Hepatitis B surface antigen was 1.7% (95% CI [1.6–1.9%]). The highest prevalence was found in the Center and South regions with respectively 2.3% (95% CI [2.0–2.7%]) and 2.2% (95% CI [1.8–2.8%]). Vaccine effectiveness (VE) was 88.6% (95% CI [81.5–93.0%]) and was higher among population aged less than 20 years 96.1% (95% CI [70.1–99.5%]) than those aged more than 20 years 59.0% (95% CI [32.0–75.3%]). VE was 85.6% (95% CI [65.8–93.9%]) is hyper-endemic areas and 89.1% (95% CI [80.3–94.0%]) in meso-endemic and hypo-endemic areas.ConclusionsThe prevalence of Hepatitis B surface antigen decreased compared to previous estimations and classify Tunisia as a low endemic country as result to the introduction of vaccination since 1995.     

Background paper to the revised recommendation for hepatitis B vaccination of persons at particular risk and for hepatitis B postexposure prophylaxis in Germany

The German Standing Committee on Vaccination (Ständige Impfkommission, STIKO) recommends vaccinating risk groups against hepatitis B and gives advice for postexposure prophylaxis. STIKO has recently revised this recommendation, focusing on: (i) classification of risk groups, (ii) duration of protection after primary immunization, and (iii) anti-HBs threshold that defines successful hepatitis B vaccination. Orientating literature reviews were performed for the first objective. Examples of population subgroups at increased risk were identified and classified into three indication groups. Systematic reviews on the duration of vaccine-induced protection identified one randomized controlled trial (RCT) and nine cohort studies. When applying the grading of recommendation, assessment, development, and evaluation (GRADE) methodology, evidence from RCTs was considered of very low quality regarding the question of whether hepatitis B can be prevented for 15 years after successful primary vaccination (anti-HBs ≥?10 IU/l) with a vaccine efficacy of 96?% against chronic hepatitis, 89?% against HBsAg positivity, and 73?% against isolated anti-HBc positivity. However, seven cohort studies showed that no cases of clinical hepatitis B or HBsAg positivity occurred during a maximum follow-up period of 10 years in settings comparable to the situation in Germany when anti-HBs ≥?10 IU/l was used to indicate vaccination success. Less than 1?% of vaccinated study participants had isolated anti-HBc positivity. GRADE assessment of two cohort studies revealed that evidence of very low quality exists that the use of anti-HBs ≥?100 IU/l to measure vaccination success leads to a lower frequency of anti-HBc positivity during follow-up than the use of anti-HBs ≥?10 IU/l. The recommendation was revised according to this evidence.     

Integrated prevention of mother-to-child transmission for human immunodeficiency virus,syphilis and hepatitis?B virus in China

ProblemChina continues to face challenges in eliminating mother-to-child transmission of human immunodeficiency virus (HIV), syphilis and hepatitis B virus (HBV).ApproachIn 2010, a programme that integrated and standardized prevention of mother-to-child transmission (PMTCT) efforts for HIV, syphilis and HBV was implemented in 1156 counties. At participating antenatal care clinics, pregnant women were offered all three tests concurrently and free of charge. Further interventions such as free treatment, prophylaxis and testing for mothers and their children were provided for HIV and syphilis.

Local setting

China’s national PMTCT HIV programme started in 2003, at which time there were no national programmes for perinatal syphilis and HBV. In 2009, the rate of maternal-to-child transmission of HIV was 8.1% (57/702). Reported congenital syphilis was 60.8 per 100 000 live births. HBV infection was 7.2% of the overall population infected.

Relevant changes

Between 2010 and 2013 the number of pregnant women attending antenatal care clinics with integrated PMTCT services increased from 5.5 million to 13.1 million. In 2013, 12.7 million pregnant women were tested for HIV, 12.6 million for syphilis and 12.7 million for HBV. Mother-to-child transmission of HIV fell to 6.7% in 2013. Data on syphilis transmission are not yet available.

Lessons learnt

Integrated PMTCT services proved to be feasible and effective, and they are now part of the routine maternal and child health services provided to infected women. The services are provided through a collaboration between maternal and child health clinics, the national and local Centers for Disease Control and Prevention, and general hospitals.     

Media and public reactions toward vaccination during the ‘hepatitis B vaccine crisis’ in China

BackgroundPublic disputations affected vaccine confidence and vaccine rates particularly when adverse events occur. The vigorous development of Internet in China provides an opportunity to observe public reaction and sentiment toward vaccination when Kangtai Hepatitis B vaccine crisis happened and evolved to a widespread debate on the internet from December 12, 2013 to January 3, 2014.MethodsThis study conducted Internet surveillance by examining three daily indicators including the daily number of relevant online news article, Sina Weibo posts and Baidu search index during the crisis. We also analyzed the sentiments of relevant original microblog posts collected from Sina Weibo platform in the crisis.ResultsA total of 17 infant deaths were reported to associated with Hepatitis B vaccination. Three major waves of high media and public attention were detected. The daily indicators reached their peaks in the second wave after the relevant vaccine was suspended by the authority (from December 20 to December 29, 2013) with 23,200 daily online news reports, 34,018 Sina Weibo posts and 17,832 Baidu search indices. There were significant correlations between the daily amount of online news, Weibo posts, and Baidu searches (p < .001). The contents analysis suggested 1343 out of 1608 (83.5%) original Weibo posts expressed negative sentiment with almost 90% in the second wave.ConclusionThis study found the Kangtai vaccine crisis raised great public attention and negative sentiment toward vaccinations on the internet in China. Policy change such as suspension of the suspected vaccine might trigger even greater reaction and more negative sentiment. The government should provide ways to address emerging public concerns after policy change to avoid misinformation and misunderstanding during such a vaccine crisis.     

Hepatitis B virus vaccination in children with steroid sensitive nephrotic syndrome: Immunogenicity and safety?

We investigated the efficacy and safety of Hepatitis B vaccine (HBVac) in steroid sensitive nephrotic syndrome (SSNS) children.     

Status and progress of hepatitis B control through vaccination in the South-East Asia Region, 1992–2015

In 2016, the Immunization Technical Advisory Group of the South-East Asia Region (SEAR) endorsed a regional goal to achieve ≤1% prevalence of hepatitis B surface antigen (HBsAg) among 5-year-old children by 2020. Chronic hepatitis B virus (HBV) infection is largely preventable with a birth dose of hepatitis B vaccine (HepB-BD) followed by two to three additional doses. We reviewed the progress towards hepatitis B control through vaccination in SEAR during 1992–2015. We summarized hepatitis B vaccination data and reviewed the literature to determine the prevalence of chronic HBV infection pre- and post-vaccine introduction. We used a mathematical model to determine post-vaccine prevalence of HBsAg among 5 year olds in countries lacking national serosurvey data and estimated the impact of vaccination on disease burden. Regional coverage with three doses of hepatitis B vaccine (HepB3) increased from 56% in 2011 to 87% in 2015. By 2016, 7 of 11 countries had introduced universal HepB-BD. Regional HepB-BD coverage increased from 9% in 2011 to 34% in 2015. In 2015, estimated HBsAg among 5 year olds was 1.1% with variability among countries. Myanmar (3.8%), Timor-Leste (2.7%), Indonesia (1.8%), and India (1%) had the highest prevalence of HBsAg. During 1992–2015, vaccination prevented approximately 16 million chronic HBV infections and 2.6 million related deaths. In 2015, around 197,640 perinatal HBV infections occurred in SEAR with majority occurring in India (62%), Bangladesh (24%), and Myanmar (8%). Myanmar had the highest rate of perinatal chronic HBV infections at 16 per 1000 live births. Despite significant progress in the control of HBV, SEAR needs to secure political commitment for elimination and consider additional strategies, such as promoting health facility births, universal birth dose administration, developing strong coordination between health sectors, and using alternative vaccine delivery methods, to improve HepB-BD coverage and subsequently achieve HBV control and elimination.     

Intradermally-administered influenza virus vaccine is safe and immunogenic in healthy adults 18–64 years of age

Background

To increase vaccine acceptance, intradermal (ID) influenza vaccine (Fluzone^® Intradermal, Sanofi Pasteur Inc.) may be an attractive alternative to intramuscular (IM) vaccination due to smaller needle and volume injected.

Methods

A multicenter, randomized (2:1 ID vs IM vaccines) study, blinded for ID vaccine lots, was conducted among 4292 adults 18–64 years of age enrolled in October 2008. Three lots of investigational trivalent influenza vaccine containing 9 μg hemagglutinin (HA) per strain in 0.1 mL administered ID with a 30 gauge, 1.5 mm long needle were compared to standard dose vaccine (0.5 mL containing 15 μg HA/strain) given IM.

Results

The post-vaccination antibody geometric mean titers (GMT) for the ID vaccine were similar to the IM vaccine (H1N1: 193.2 vs. 178.3, H3N2: 246.7 vs. 230.7, and B: 102.5 vs. 126.9). Non-inferiority was met for the ID vaccine compared to IM vaccine as assessed by antibody GMT ratios (IM/ID) for all three virus strains (H1N1: 0.92, H3N2: 0.94, and B: 1.24). Seroconversion rates were non-inferior for H1N1 and H3N2, but not for B (ID vs. IM: H1N1: 61.2% vs. 60.5%, H3N2: 75.3% vs. 74.8%, and B: 46.2% vs. 54.2%). Seroprotection (HAI titer ≥1:40) rates were similar between groups (ID vs. IM, H1N1: 91.1% vs. 91.7%, H3N2: 90.7% vs. 91.4%, and B: 87.4% vs. 89.3%). Local injection site reactions overall were more common with ID than IM vaccine (ID vs. IM: 89.2% vs. 60.2%), but were usually grade 1 or 2 and transient. The frequencies of local injection site pain and systemic reactions were similar between vaccine groups, except more myalgia with IM vaccine.

Conclusions

The ID vaccine elicited immune responses comparable to IM vaccine except for the seroconversion rate to B virus. With the exception of pain, local injection site reactions were more common with the ID vaccine, but well-tolerated and of short duration.

Trial registration

ClinicalTrials.gov identifier: NCT00772109.     

No association between HPV vaccination and infertility in U.S. females 18–33 years old

BackgroundHuman papillomavirus (HPV) vaccines have been recommended as primary prevention of HPV-related cancers for over 10 years in the United States, and evidence reveals decreased incidence of HPV infections following vaccination. However, concerns have been raised that HPV vaccines could decrease fertility. This study examined the relationship between HPV immunization and self-reported infertility in a nationally representative sample.MethodsData from the 2013–2016 National Health and Nutrition Examination Survey were analyzed to assess likelihood of self-reported infertility among women aged 20 to 33, who were young enough to have been offered HPV vaccines and old enough to have been queried about infertility (n = 1114). Two logistic regression models, stratified by marital history, examined potential associations between HPV vaccination and infertility. Model 1 assessed the likelihood of infertility among women who had never been pregnant or whose pregnancies occurred prior to HPV vaccination. Model 2 accounted for the possibility of latent and/or non-permanent post-vaccine infertility by including all women 20–33 years old who reported any 12-month period of infertility.Results8.1% reported any infertility. Neither model revealed any association between HPV vaccination at any age and self-reported infertility, regardless of marital status.ConclusionThere was no evidence of increased infertility among women who received the HPV vaccine. These results provide further evidence of HPV vaccine safety and should give providers confidence in recommending HPV vaccination. Further research should explore protective effects of HPV vaccines on female and male fertility.     

Antibody kinetics among 8–10 years old respondents to hepatitis B vaccination in a low endemic country and the effect of a booster dose given 5 or 10 years later

Few data are available concerning the persistence of anti-HBs and the effect of booster doses given several years post-vaccination against hepatitis B during preadolescence. The objective of this open-labelled clinical trial was to evaluate the persistence of antibodies after vaccination with three paediatric doses of Engerix-B at the age of 8–10 years and the effect of a booster dose given 5 (Group Y5) or 10 (Group Y10) years later. Anti-HBs were measured before and one month post-primary vaccination, then 5 and 10 years later, before the booster dose, as well as one month and 1 year post-booster. The anamnestic response was defined as a ≥fourfold increase of anti-HBs post-booster (≥10 IU/L) when compared to pre-booster. Ten years post-primary vaccination, 559 of the 652 initially randomized subjects (86%) were eligible for analysis. Group Y5, 5 years post-booster results: 99% of subjects had detectable levels of antibodies and 96% a titer ≥10 IU/L. The anti-HBs GMTs decreased from 114,489 IU/L one month post-booster to 3354 IU/L 5 years later. Group Y10 results: 10 years post-primary vaccination 96% of subjects had a detectable level of anti-HBs and 85% were above the threshold of 10 IU/L. The GMTs one month post-booster were 31,030 IU/L. The challenge with a booster demonstrated an anamnestic response in 99% of subjects in group Y5 and 100% of subjects in group Y10. All subjects were anti-HBc negative. The booster doses were well tolerated. The excellent anamnestic response observed after the booster dose demonstrates the persistence of immunity in virtually all young adults vaccinated at the age of 8–10 with three paediatric doses of Engerix-B.     

Lasting immune memory against hepatitis B following challenge 10–11 years after primary vaccination with either three doses of hexavalent DTPa-HBV-IPV/Hib or monovalent hepatitis B vaccine at 3, 5 and 11–12 months of age

BackgroundThe combined hexavalent diphtheria–tetanus–pertussis–hepatitis B-inactivated poliomyelitis – Haemophilus influenzae type b conjugate vaccine (Infanrix hexa™; DTPa-HBV-IPV/Hib: GlaxoSmithKline Vaccines) induces robust responses to the HBV component when administered at 3, 5 and 11–12 months of age. We assessed long term HBV antibody persistence 10–11 years after primary vaccination in infancy.MethodsAntibody persistence and immune memory were assessed post-primary vaccination at 3, 5, 11–12 months with DTPa-HBV-IPV/Hib, or monovalent HBV vaccine (Engerix™ B, GlaxoSmithKline Vaccines) co-administered with DTPa-IPV/Hib (Infanrix™-IPV/Hib, GlaxoSmithKline Vaccines) in 185 children aged 11–12 years. Blood samples were collected before and 1 month after a challenge dose of Engerix™ B (10 μg dose).Results10–11 years after primary vaccination the percentage of subjects with persisting anti-HBs antibody concentrations ≥10 mIU/ml was 48.4% in the DTPa-HBV-IPV/Hib group and 58.4% in the DTPa-IPV/Hib + HBV group. After the HBV challenge dose, the percentage with anti-HBs ≥100 mIU/ml increased from 14.7% to 93.6% in the DTPa-HBV-IPV/Hib group and 19.1% to 94.4% in the DTPa-IPV/Hib + HBV group. Anti-HBs GMCs increased by at least 187-fold in each group. An anamnestic response (≥4-fold increase in initially seropositive or anti-HBs concentration ≥10 mIU/ml in initially seronegative subjects) was observed in 96.8% and 96.6% of subjects in the DTPa-HBV-IPV/Hib and DTPa-IPV/Hib + HBV groups, respectively. No serious adverse events occurred that were considered related to challenge vaccination.ConclusionAdministration of HBV as part of a combination vaccine or as a monovalent vaccine induced long lasting immune memory against HBV in children primed at 3, 5 and 11 months of age. Antibody persistence and immune memory were similar, suggesting that protection afforded by DTPa-HBV-IPV/Hib and monovalent HBV vaccines, is likely to be of similar duration. The administration of HBV challenge dose 10–11 years after the 3, 5, 11–12 months primary schedule induced strong anamnestic responses and was well tolerated.This study is registered at www.clinicaltrials.gov NCT01138098.     

Health-related quality of life of firefighters and police officers 8.5 years after the air disaster in Amsterdam

Background In 1992 a cargo aircraft crashed into apartment buildings in Amsterdam. In the troublesome aftermath rumours emerged on potential toxic exposures and health consequences. The aim of this study is to assess the long-term impact of this disaster on the health-related quality of life (HRQoL) of professional assistance workers. Methods Historic cohort study, using questionnaires to assess occupational disaster exposure, HRQoL (SF36), and background variables, at on average 8.5 years post-disaster. Participating were the exposed professional firefighters (n = 334) and police officers (n = 834) who reported disaster-related task(s), and their non-exposed colleagues who did not report such tasks (n = 194, and n = 634, respectively). Results Multivariate logistic regression analysis showed that exposed workers reported a significantly lower physical HRQoL and vitality than non-exposed workers. Exposed police officers also reported a lower mental HRQoL. Among exposed workers, a lower HRQoL was reported significantly more often by workers who had a close one affected by the disaster; by firefighters who rescued people, cleaned-up, or witnessed the immediate disaster scene; and by police officers who supported the injured. Exposed police officers who perceived the disaster as ‘not bad’ reported a lower HRQoL less often than those to whom it was ‘the worst ever’. Conclusions This study demonstrates that professional disaster assistance workers are at risk for a lower HRQoL, even after years. An erratum to this article can be found at     

Self-reported hepatitis A vaccination as a predictor of hepatitis A virus antibody protection in U.S. adults: National Health and Nutrition Examination Survey 2007–2012

ObjectivesTo estimate the predictive value of self-reported hepatitis A vaccine (HepA) receipt for the presence of hepatitis A virus (HAV) antibody (anti-HAV) from either past infection or vaccination, as an indicator of HAV protection.MethodsUsing 2007–2012 National Health and Nutrition Examination Survey data, we assigned participants to 4 groups based on self-reported HepA receipt and anti-HAV results. We compared characteristics across groups and calculated three measures of agreement between self-report and serologic status (anti-HAV): percentage concordance, and positive (PPV) and negative (NPV) predictive values. Using logistic regression we investigated factors associated with agreement between self-reported vaccination status and serological results.ResultsDemographic and other characteristics varied significantly across the 4 groups. Overall agreement between self-reported HepA receipt and serological results was 63.6% (95% confidence interval [CI] 61.9–65.2); PPV and NPV of self-reported vaccination status for serological result were 47.0% (95% CI 44.2–49.8) and 69.4% (95% CI 67.0–71.8), respectively. Mexican American and foreign-born adults had the highest PPVs (71.5% [95% CI 65.9–76.5], and 75.8% [95% CI 71.4–79.7]) and the lowest NPVs (21.8% [95% CI 18.5–25.4], and 20.0% [95% CI 17.2–23.1]), respectively. Young (ages 20–29 years), US-born, and non-Hispanic White adults had the lowest PPVs (37.9% [95% CI 34.5–41.5], 39.1% [95% CI, 36.0–42.3], and 39.8% [36.1–43.7]), and the highest NPVs (76.9% [95% CI 72.2–81.0, 78.5% [95% CI 76.5–80.4)], and 80.6% [95% CI 78.2–82.8), respectively. Multivariate logistic analyses found age, race/ethnicity, education, place of birth and income to be significantly associated with agreement between self-reported vaccination status and serological results.ConclusionsWhen assessing hepatitis A protection, self-report of not having received HepA was most likely to identify persons at risk for hepatitis A infection (no anti-HAV) among young, US-born and non-Hispanic White adults, and self-report of HepA receipt was least likely to be reliable among adults with the same characteristics.     

Aggregation and antigenicity of virus like particle in salt solution—A case study with hepatitis B surface antigen

The phenomenon of aggregation of virus-like particles (VLPs) in salt solution and the corresponding effect upon antigenicity was reported. Asymmetrical flow field-flow fractionation (AF4) combined with multi-angle laser light scattering (MALLS) was used to characterize the size and the aggregation behavior of hepatitis B surface antigen (HBsAg). The average diameter of HBsAg VLP was 22.8 ± 0.4 nm and it tended to aggregate in salt solution to form large particles and the antigenicity changed accordingly. In 0–4 M NaCl solution, part of HBsAg molecules aggregated rapidly into oligomeric particles (OP), whose diameter distributed from 25 to 40 nm, and the antigenicity slightly decreased about 10%. The aggregation reaction is reversible. After removing NaCl, both size and antigenicity could recover to normal level (92–96%). By contrast, the aggregation process is more complicated in (NH₄)₂SO₄ solution. Most of HBsAg particles aggregated into OP and further aggregated into polymeric particles (PP). The diameter of the PP could reach 40 to 140 nm. The concentration of (NH₄)₂SO₄ had remarkable influence upon the rate of aggregation. When concentration of (NH₄)₂SO₄ was below 1 M, most of HBsAg aggregated only into OP in 1 h. While with concentration of (NH₄)₂SO₄ above 1 M, most of particles formed PP within 1 h. The aggregation process to PP was irreversible. After removing (NH₄)₂SO₄, the large aggregates could not recover to normal particles and the remaining antigenicity was below 30%.     

Antibody persistence and booster response 68 months after vaccination at 2–10 years of age with one dose of MenACWY-TT conjugate vaccine

BackgroundWe evaluated antibody persistence up to 68 months (M) post-vaccination with a quadrivalent meningococcal serogroups A, C, W and Y tetanus toxoid conjugate vaccine (MenACWY-TT) or a licensed monovalent MenC conjugate vaccine (MenC-CRM₁₉₇) and subsequent booster responses to MenACWY-TT in healthy European children.MethodsIn the initial study (NCT00674583), healthy children, 2–10 years of age, were randomized to receive a single dose of either MenACWY-TT or MenC-CRM₁₉₇. In the follow-up study, we present the persistence at 32, 44, 56, and 68 M post-vaccination, overall and stratified by age (2–5 and 6–10 years), and the immunogenicity and safety of MenACWY-TT administered to all study participants at M68 post-primary vaccination.ResultsAt M68, 33.3% (age group 2–5 years) and 47.1% (age group 6–10 years) of the children vaccinated with MenACWY-TT, and 50.0% (age group 2–5 years) and 75.9% (age group 6–10 years) vaccinated with MenC-CRM₁₉₇ retained titers ≥1:8 for MenC, as assessed by a serum bactericidal assay using rabbit complement (rSBA). In the MenACWY-TT recipients, the percentages of children retaining rSBA titers ≥1:8 for MenA, MenW, and MenY were 81.7%, 47.3% and 66.7% in age group 2–5 years and 91.8%, 58,8% and 76.5% in age group 6–10 years, respectively. The booster dose induced robust responses (100% for all serogroups) and was well-tolerated.ConclusionsAntibody persistence (rSBA titers ≥ 1:8) for serogroups A, W and Y was observed in more than 50.0% of the children 68 M after receiving one dose of MenACWY-TT; for MenC, antibody persistence was observed in more than one third of MenACWY-TT and more than half of MenC-CRM₁₉₇ recipients. Vaccination with a booster dose of MenACWY-TT induced robust immune responses for all serogroups.