An investigational tetravalent meningococcal serogroups A, C, W-135 and Y-tetanus toxoid conjugate vaccine co-administered with Infanrix™ hexa is immunogenic, with an acceptable safety profile in 12-23-month-old children

Tetravalent meningococcal serogroups ACWY conjugate vaccines will provide an advantage to those at most risk of invasive meningococcal disease; namely young children. Co-administration of ACWY-TT with DTaP-HBV-IPV/Hib was assessed in a randomized trial in 793 children aged 12-23 months. Pre-specified criteria for non-inferiority of immunogenicity following co-administration versus separate ACWY-TT and DTaP-HBV-IPV/Hib administration were reached. One month post-vaccination, ≥97.3% of ACWY-TT vaccinees had rSBA titres ≥1:8 (all serogroups). Seroprotection/seropositivity rates against DTaP-HBV-IPV/Hib antigens were ≥98.2%. The safety profile of co-administration was similar to that of DTaP-HBV-IPV/Hib alone. ACWY-TT and DTaP-HBV-IPV/Hib co-administration during the second year would facilitate introduction of ACWY-TT into routine toddler vaccination schedules.     

Healthcare workers’ knowledge,beliefs, and coverage regarding vaccinations in critical care units in Italy

BackgroundLow rates of vaccine coverage have resulted in a resurgence of several vaccine-preventable diseases in many European countries. Routine vaccination of healthcare workers (HCWs) is important to reduce disease transmission, and to promote vaccine awareness and acceptance in the population. The objectives of this cross-sectional study were to investigate knowledge and beliefs about vaccines and to evaluate self-reported immunization coverage with vaccines recommended for HCWs. Additionally, the effects of several factors on these outcomes have been evaluated.MethodsA survey was conducted between September and November 2018 among a random sample of HCWs in cardiac, adult, and neonatal critical care units of 8 randomly selected hospitals across the Campania and Calabria Regions in Italy. Multivariate logistic and linear regression analysis has been performed.ResultsA total 531 HCWs returned the questionnaire for a response rate of 54.9%. Based on a vaccination knowledge score ranging from 0 to 9, more than half of the participants (55.4%) knew few of the vaccines recommended for HCWs (≤3 correct answers), 16.2% knew some vaccines (4–6 correct answers), and 28.4% knew most vaccines (≥7 correct answers), and only 13.2% knew all the vaccines recommended for HCWs. However, two-thirds (62.2%) knew that hepatitis B and influenza vaccines were recommended, and this knowledge was significantly higher among females (p < 0.001), among HCWs aged between 50 and 59 years (p = 0.01) compared with those aged < 30 years, and in those who search for information about recommended vaccines for HCWs (p = 0.012). The vaccine knowledge was significantly lower among nurses and nursing supporting staff compared with physicians (p = 0.032). Approximately two-thirds (62.7%) of HCWs considered themselves at risk of contracting vaccine-preventable infectious diseases during their professional practice. High rates of coverage were self-reported for hepatitis B (96.3%), tetanus and pertussis (93.7%), whereas they were lower for measles/mumps/rubella (80.5%), chickenpox (65.3%), and influenza (35.8%). Only 9.2% of HCWs reported prior receipt of all recommended vaccines. Male HCWs were less likely to report prior receipt of all recommended vaccines (p = 0.011). HCWs aged between 30 and 39 years compared with those aged < 30 years (p = 0.001) and those who knew some (p < 0.001) and most (p = 0.007) of all vaccines recommended for HCWs were more likely to self-report to be immunized.ConclusionsAdditional training about the vaccinations is needed to improve HCWs knowledge and to address specific concerns which may lead to better uptake among this group.     

Vaccine administration error rates at a large academic medical center and its affiliated clinics – Familiarity matters

ObjectiveThe purpose of this study was to track and describe the absolute number of vaccine administration errors and corresponding error rates over time and by patient age and vaccine type.MethodsTotal vaccines administered to patients aged 0 through 19 years 364 days from 1/1/2006 through 12/31/2017 at a large academic health system in the Midwest United States with primary, specialty and school-based clinics, and a pediatric hospital were obtained from an electronic medical record. Vaccine administration errors over the same time period for the same patient criteria were analyzed from the health system’s incident reporting system and further compared to the frequency of all incidents reported. Vaccine administration error rates were calculated. Data were analyzed by patient age, vaccine type and year administered.ResultsOf the 1,431,206 vaccine doses given, 552 vaccine administration errors were identified (0.04%). The highest error rates occurred in children aged 2, 3, and 19 years. Vaccine types with the highest error rate were Td, rabies and pneumococcal polysaccharide vaccines. Overall vaccine doses given and errors reported increased over the study period. However, the increase was disproportionate, resulting in an increase in the error rate initially followed by a stabilization at the end of the study period.ConclusionsVaccine administration errors are uncommon. The error rate appears to be stabilizing. Errors are more likely at ages when vaccines are not commonly given, with vaccines that have age-specific dosing and with vaccines that are given less often. This suggests more safety checks are needed for vaccines that are rarely used or given off-schedule, and manufacturers should avoid vaccines with age-specific dosing.     

Higher mass meningococcal group C-tetanus toxoid vaccines conjugated with carbodiimide correlate with greater immunogenicity

To examine the link between meningococcal C (MenC) vaccine size and immunogenic response, a panel of MenC glycoconjugate vaccines were prepared differing in chain length, molar mass and hydrodynamic volume. The preparations consisted of different lengths of MenC polysaccharide (PS) covalently linked to monomeric purified tetanus toxoid (TT) carrier protein using the coupling reagent ethylcarbodiimide hydrochloride (EDC). Size exclusion chromatography with multi-angle light scattering (SEC-MALS) and viscometry analysis confirmed that the panel of MenC-TT conjugates spanned masses of 191,500 to 2,348,000 g/mol, and hydrodynamic radii ranging from 12.1 to 47.9 nm. The two largest conjugates were elliptical in shape, whereas the two smallest conjugates were more spherical. The larger conjugates appeared to fit a model described by multiple TTs with cross-linked PS, typical of lattice-like networks described previously for TT conjugates, while the smaller conjugates were found to fit a monomeric or dimeric TT configuration. The effect of vaccine conjugate size on immune responses was determined using a two-dose murine immunization. The two larger panel vaccine conjugates produced higher anti-MenC IgG1 and IgG2b titres after the second dose. Larger vaccine conjugate size also stimulated greater T-cell proliferative responses in an in vitro recall assay, although cytokines indicative of a T-helper response were not measurable. In conclusion, larger MenC-TT conjugates up to 2,348,000 g/mol produced by EDC chemistry correlate with greater humoral and cellular murine immune responses. These observations suggest that conjugate size can be an important modulator of immune response.     

Children vaccination coverage surveys: Impact of multiple sources of information and multiple contact attempts

BackgroundMonitoring vaccination coverage is an essential component of vaccination program evaluation. In Québec (Canada), children vaccination coverage surveys are conducted every two years since 2006. The objectives of this study were to evaluate the impact of supplementing data based on vaccination booklets with data from vaccine providers, on the final estimated vaccination coverage and to compare vaccination coverage between respondents to each survey contact attempt.MethodsData from six cross-sectional surveys were used, which included 3508 children aged 2 years. Parents were invited to transcribe the information available in their child’s vaccination booklet on the questionnaire received by mail. The survey included a maximum of 4 contact attempts to obtain a response. Data were completed among vaccine providers identified by parents. The main outcome was a complete vaccination status by 24 months of age.ResultsThe addition of data from vaccine providers to those present in vaccination booklets increased the proportion of children fully vaccinated from 5.5% to 23.7% depending on the survey year. The proportion of children fully vaccinated by 24 months of age estimated among respondents to contact 1 was only 2.1% higher than the estimates among all respondents.ConclusionsWithout validation among vaccine providers for children with missing doses according to vaccination booklets, results underestimated vaccination coverage in the target population. Conducting multiple contact attempts increased the response rate but had limited impact on the validity of estimates. It would be useful in future surveys to present the coverage obtain from respondents to each contact attempt.     

Safety data from the MenB-FHbp clinical development program in healthy individuals aged 10 years and older

BackgroundThe MenB-FHbp vaccine (Trumenba®) is licensed in various countries for the prevention of meningococcal serogroup B disease in individuals ≥ 10 years of age. The clinical development program included 11 completed trials where, in each trial, MenB-FHbp had an acceptable safety profile after a primary vaccination series was administered to individuals 10–65 years of age. However, the detection of potential rare events was limited because of individual clinical trial size. The current safety analysis evaluates pooled reactogenicity and other adverse events (AEs) reported in these trials to identify new safety signals not detectable in individual trials.MethodsEleven trials contributed safety data, of which 10 recorded local and systemic reactogenicity events; 8 of the trials were controlled, and reactogenicity data were pooled for 7 of these 8 trials. Additional AE evaluations included immediate AEs (IAEs), medically attended AEs (MAEs), serious AEs (SAEs), newly diagnosed chronic medical conditions (NDCMCs), and autoimmune or neuroinflammatory conditions.ResultsLocal and systemic reactions were more frequent in the MenB-FHbp group (n = 15,294) compared with controls (n = 5509), although most reactions were transient and mild to moderate in severity. Frequencies of IAEs, SAEs, MAEs, NDCMCs, and autoimmune or neuroinflammatory conditions were similar between the MenB-FHbp and control groups.ConclusionsMenB-FHbp demonstrated a favorable safety and tolerability profile in the clinical development program of > 15,000 vaccine recipients ≥ 10 years of age. No new safety signals were identified in the pooled analysis compared with data from the individual trials. Continued postmarketing safety surveillance is important for the identification of rare events.Clinicaltrials.gov: NCT01299480; NCT000808028; NCT00879814; NCT00780806; NCT01352845; NCT01352793; NCT01461993; NCT01323270; NCT01830855; NCT01461980; NCT01768117.     

2015 - 2017年无锡市含无细胞百白破成分疫苗预防接种安全性评价

目的 评价无锡市无细胞百白破疫苗（DTaP）和无细胞百白破-灭活脊髓灰质炎- b型流感嗜血杆菌联合疫苗（DTaP - IPV - Hib）的预防接种安全性。方法 分别通过中国AEFI监测信息管理系统和无锡市免疫规划信息管理系统收集AEFI监测数据和疫苗接种数据，采用描述性流行病学方法对2015 - 2017年无锡市的DTaP和DTaP - IPV - Hib接种后的不良反应进行分析。结果 2015 - 2017年无锡市接种DTaP 、DTaP - IPV - Hib一般反应报告发生率分别为327.67/10万、268.23/10万，异常反应报告发生率分别为19.79/10万、15.58/10万。DTaP和DTaP - IPV - Hib 的一般反应和异常反应均以加强免疫为主，集中在接种后0～1 d。一般反应均主要表现为红肿（80.73%，65.31%）、硬结（45.14%，33.33%）和发热（22.69%，44.22%），异常反应主要表现均以过敏性皮疹为主（58.11%，50%）。结论 DTaP和DTaP - IPV - Hib的不良反应报告发生率无差别，均主要发生在加强免疫期间，具有良好的预防接种安全性。     

Some properties of low-molecular-weight tetanus antitoxin

After intravenous injection of tetanus antitoxin obtained by tryptic digestion of Diaferm-3 horse immunoglobulin, purification, and concentration of the active fragments, the antitoxin was excreted by rabbits 3 times faster than after injection of the original Diaferm-3 antitoxin. After injection of the fragmented antitoxin its excretion continued until the 6th days, whereas after injection of Diaferm-3 antitoxin its excretion continued until the 19th day; in the first case much less antitoxin was excreted than in the second (2% and 3.5% respectively). In both cases the antitoxin excreted in the urine consisted of monovalent Fab' fragments which caused delay of precipitation in the cross reaction in agar gel between tetanus toxoid and antitetanus serum. The Fab' gragment obtained by this method possessed anaphylactogenic properties.L'vov Medical Institute. Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 3, pp. 331–333, March, 1976.