Motivational interviewing for maternal Immunizations: Intervention development

Background and ObjectiveVaccine uptake during pregnancy remains low. Our objectives were to describe 1) development and adaptation of a clinician communication training intervention for maternal immunizations and 2) obstetrics and gynecology (ob-gyn) clinician and staff perspectives on the intervention and fit for the prenatal care context.MethodsDesign of the Motivational Interviewing for Maternal Immunizations (MI4MI) intervention was based on similar communication training interventions for pediatric settings and included presumptive initiation of vaccine recommendations (“You’re due for two vaccines today”) combined with motivational interviewing (MI) for hesitant patients. Interviews and focus group discussions were conducted with ob-gyn clinicians and staff in five Colorado clinics including settings with obstetric physicians, certified nurse midwives (CNMs), and clinician-trainees. Participants were asked about adapting training to the ob-gyn setting and their implementation experiences. Feedback was incorporated through iterative changes to training components.ResultsInterview and focus group discussion results from participants before (n = 3), during (n = 11) and after (n = 25) implementation guided intervention development and adaptation. Three virtual, asynchronous training components were created: a video and two interactive modules. This virtual format was favored due to challenges attending group meetings; however, participants noted opportunities to practice skills through role-play were lacking. Training modules were adapted to include common challenging vaccine conversations and live-action videos. Participants liked interactive training components and use of adult learning strategies. Some participants initially resisted the presumptive approach but later found it useful after applying it in their practices. Overall, participants reported that MI4MI training fit well with the prenatal context and recommended more inclusion of non-clinician staff.ConclusionsMI4MI training was viewed as relevant and useful for ob-gyn clinicians and staff. Suggestions included making training more interactive, and including more complex scenarios and non-clinician staff.     

Thrombosis and thromboembolism: Brighton collaboration case definition and guidelines for data collection,analysis, and presentation of immunization safety data

This is a Brighton Collaboration case definition of thrombosis and thromboembolism to be used in the evaluation of adverse events following immunization, and for epidemiologic studies for the assessment of background incidence or hypothesis testing. The case definition was developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of SARS-CoV-2 vaccines. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and defined levels of certainty, after an exhaustive review of the literature and expert consultation. The document underwent peer review by the Brighton Collaboration Network and by selected expert reviewers prior to submission.     

Reference set for performance testing of pediatric vaccine safety signal detection methods and systems

BackgroundSafety signal detection in spontaneous reporting system databases and electronic healthcare records is key to detection of previously unknown adverse events following immunization. Various statistical methods for signal detection in these different datasources have been developed, however none are geared to the pediatric population and none specifically to vaccines. A reference set comprising pediatric vaccine-adverse event pairs is required for reliable performance testing of statistical methods within and across data sources.MethodsThe study was conducted within the context of the Global Research in Paediatrics (GRiP) project, as part of the seventh framework programme (FP7) of the European Commission. Criteria for the selection of vaccines considered in the reference set were routine and global use in the pediatric population. Adverse events were primarily selected based on importance. Outcome based systematic literature searches were performed for all identified vaccine-adverse event pairs and complemented by expert committee reports, evidence based decision support systems (e.g. Micromedex), and summaries of product characteristics. Classification into positive (PC) and negative control (NC) pairs was performed by two independent reviewers according to a pre-defined algorithm and discussed for consensus in case of disagreement.ResultsWe selected 13 vaccines and 14 adverse events to be included in the reference set. From a total of 182 vaccine-adverse event pairs, we classified 18 as PC, 113 as NC and 51 as unclassifiable. Most classifications (91) were based on literature review, 45 were based on expert committee reports, and for 46 vaccine-adverse event pairs, an underlying pathomechanism was not plausible classifying the association as NC.ConclusionA reference set of vaccine-adverse event pairs was developed. We propose its use for comparing signal detection methods and systems in the pediatric population.     

某社区2019年第二类疫苗接种疑似预防接种异常反应监测结果

目的了解某社区第二类疫苗接种及疑似预防接种异常反应(AEFI)情况。方法通过查询疫苗出入库系统和中国免疫规划信息管理系统,对2019年该社区第二类疫苗使用及AEFI报告情况进行分析。结果2019年,该社区接种门诊共接种第二类疫苗21种7449剂,接种数最多的是13价肺炎疫苗(784剂)。接种数居前6位的依次为13价肺炎疫苗、ACYW135群流脑多糖疫苗、轮状病毒疫苗、百白破-IPV-HIB五联疫苗、手足口EV71疫苗、九价人乳头瘤疫苗。累计报告AEFI病例94例,发生率为1.26%;一般反应占96.81%,异常反应占3.19%。报告AEFI疫苗共12种,报告发生率居前6位的分别为13价肺炎疫苗、百白破-IPV-HIB五联疫苗、百白破-IPV-HIB四联疫苗、手足口EV71疫苗、九价HPV疫苗、AC结合流脑疫苗。结论第二类疫苗品种接种量均有所增加,AEFI报告发生率有所波动,需加强监测。     

Investigating the association of receipt of seasonal influenza vaccine with occurrence of anesthesia/paresthesia and severe headaches,Canada 2012/13–2016/17, the Canadian Vaccine Safety Network

BackgroundConcern about adverse events following immunization is frequently cited by both those who receive or decline vaccines. Neurological adverse events are especially concerning.ObjectivesOur aim was to detect associations between seasonal influenza vaccination and the occurrence of severe anesthesia/paresthesia or severe headaches.MethodsData were analyzed from the Canadian National Vaccine Safety network. Events occuring on days 0–7 were self-reported and prevented daily activity, led to school or work absenteeism, or required medical attention. Controls were the previous year’s vaccinees; events in controls were collected prior to the start of the influenza vaccination program of each year (2012/13 through 2016/17). Multivariable logistic regression was used to determine the association between seasonal influenza vaccination and the occurrence of anesthesia/paresthesia or severe headaches.ResultsThe total sample was 107,565 for investigating anesthesia/paresthesia and 97,420 for investigating severe headaches. Anesthesia/paresthesia was reported by 104/107,565 (0.10%) participants; 63/69,129 (0.09%) vaccinees and 41/38,436 (0.11%) controls (adjusted odds ratio (aOR) = 0.89; 95% CI = 0.60, 1.32). Severe headaches were reported by 1361/97,420 (1.40%) participants; 907/61,463 (1.48%) vaccinees and 454/35,957 (1.26%) controls (aOR = 1.21; 95% CI = 1.08, 1.36). No specific vaccine product was associated with severe headaches.ConclusionsOur study found no association between severe anesthesia/paresthesia and seasonal influenza vaccination. While there was an association with severe headaches as an adverse event following influenza vaccination, the rates of these events are similar to rates reported from clinical trials and are not a cause for additional concern.     

The effect of maternal antibodies on the cellular immune response after infant vaccination: A review

During the last few decades, maternal immunization as a strategy to protect young infants from infectious diseases has been increasingly recommended, yet some issues have emerged. Studies have shown that for several vaccines, such as live attenuated, toxoid and conjugated vaccines, high maternal antibody titers inhibit the infant’s humoral immune response after infant vaccination. However, it is not clear whether this decreased antibody titer has any clinical impact on the infant’s protection, as the cellular immune responses are often equally important in providing disease protection and may therefore compensate for diminished antibody levels. Reports describing the effect of maternal antibodies on the cellular immune response after infant vaccination are scarce, probably because such studies are expensive, labor intensive and utilize poorly standardized laboratory techniques. Therefore, this review aims to shed light on what is currently known about the cellular immune responses after infant vaccination in the presence of high (maternal) antibody titers both in animal and human studies. Overall, the findings suggest that maternally derived antibodies do not interfere with the cellular immune responses after infant vaccination. However, more research in humans is clearly needed, as most data originate from animal studies.     

Resurgence of pertussis in Taiwan during 2009–2015 and its impact on infants

Background/purposePertussis incidence markedly decreased due to universal vaccination, but outbreaks had been noted worldwide in recent decade. This study was conducted to know the epidemiology of pertussis and its impact on infants in Taiwan.MethodsEpidemiologic parameters for confirmed pertussis cases were collected from the Taiwan Centers for Disease Control. The incidence of each age group over years was calculated using population data. We also did retrospective reviews of laboratory-confirmed pertussis cases in NTUH to analyze clinical characteristics and disease severity.ResultsA total of 668 confirmed pertussis cases were obtained from the Taiwan CDC open database between 2003 and 2017. There was higher incidence during the period 2009–2015, with a mean incidence of 0.27 cases per 100,000 population, about 2-fold increase compared with mean incidence of 0.12 cases per 100,000 population during the period 2003–2008. Infants accounted for the highest proportion of all cases (49.8%), with mean incidence of 16.1 cases per 100,000 people per year during 2009–2015, and a trend of increase was found from 2003 to 2015. In NTUH, a total of 17 laboratory-confirmed pertussis cases were diagnosed during 2012–2016, and 14 cases were young infants. Among them, 9 infants had been admitted to intensive care unit and 2 infant needed invasive ventilator support.ConclusionThere was a resurgence of pertussis during 2009–2015 and it had significant impact on infants. Young infants with pertussis may be severe and need intensive care, so preventive strategy may be advocated for them.     

Intranasal immunization with protective antigen of Bacillus anthracis induces a long-term immunological memory response

Although intranasal vaccination has been shown to be effective for the protection against inhalational anthrax, establishment of long-term immunity has yet to be achieved. Here, we investigated whether intranasal immunization with recombinant protective antigen (rPA) of Bacillus anthracis induces immunological memory responses in the mucosal and systemic compartments. Intranasal immunization with rPA plus cholera toxin (CT) sustained PA-specific antibody responses for 6 months in lung, nasal washes, and vaginal washes as well as serum. A significant induction of PA-specific memory B cells was observed in spleen, cervical lymph nodes (CLNs) and lung after booster immunization. Furthermore, intranasal immunization with rPA plus CT remarkably generated effector memory CD4⁺ T cells in the lung. PA-specific CD4⁺ T cells preferentially increased the expression of Th1- and Th17-type cytokines in lung, but not in spleen or CLNs. Collectively, the intranasal immunization with rPA plus CT promoted immunologic memory responses in the mucosal and systemic compartments, providing long-term immunity.     

Novel lipopeptides of ESAT-6 induce strong protective immunity against Mycobacterium tuberculosis: Routes of immunization and TLR agonists critically impact vaccine’s efficacy

Mycobacterium tuberculosis (Mtb), the bacterial cause of tuberculosis, is a leading infectious agent worldwide. The development of a new vaccine against Mtb is essential to control global spread of tuberculosis, since the current vaccine BCG is not very effective and antibiotic resistance is a serious, burgeoning problem. ESAT-6 is a secreted protein of Mtb, which is absent in BCG but has been implicated in inducing protective immunity against Mtb. Peptide based subunit vaccines are attractive due to their safety and high specificity in eliciting immune responses, but small synthetic peptides are usually not very immunogenic. We have designed a novel subunit vaccine for Mtb by using simple lipid (palmitic acid) modified derivatives of peptides from ESAT-6 protein corresponding to dominant human T cell epitopes and examined their ability to stimulate protective immunity against Mtb by intranasal and subcutaneous immunization in mice. We also investigated how individual TLR agonists as adjuvants (PolyI:C, MPL and GDQ) contribute to enhancing the induced immune responses and resulting protective efficacy of our vaccine. We observed that single C-terminal palmitoyl-lysine modified lipopeptides derived from ESAT-6 induce significant cellular immune responses on their own upon mucosal and subcutaneous immunizations. Intriguingly, a combination of immunogenic lipopeptides of ESAT-6 antigen exhibited local (pulmonary) and systemic immune responses along with efficient protective efficacy when administered intranasally or subcutaneously. Surprisingly, combination of ESAT-6 derived lipopeptides with a TLR-4 agonist (MPL) enhanced protection, whereas TLR-3 (Poly I:C) and TLR-7/8 agonists (gardiquimod, GDQ) led to reduced protection associated with specific local and systemic immune modulation. Our studies demonstrate the potential of ESAT-6 derived lipopeptides as a promising vaccine candidate against Mtb, and emphasize that selection of adjuvant is critical for the success of vaccines. These findings demonstrate the promise of synthetic lipopeptides as the basis of a subunit vaccine for TB.