DTaP Vaccine Research Articles

Development of a TLR7/8 agonist adjuvant formulation to overcome early life hyporesponsiveness to DTaP vaccination

Infection is the most common cause of mortality early in life, yet the broad potential of immunization is not fully realized in this vulnerable population. Most vaccines are administered during infancy and childhood, but in some cases the full benefit of vaccination is not realized in-part. New adjuvants are cardinal to further optimize current immunization approaches for early life. However, only a few classes of adjuvants are presently incorporated in vaccines approved for human use. Recent advances in the discovery and delivery of Toll-like receptor (TLR) agonist adjuvants have provided a new toolbox for vaccinologists. Prominent among these candidate adjuvants are synthetic small molecule TLR7/8 agonists. The development of an effective infant Bordetella pertussis vaccine is urgently required because of the resurgence of pertussis in many countries, contemporaneous to the switch from whole cell to acellular vaccines. In this context, TLR7/8 adjuvant based vaccine formulation strategies may be a promising tool to enhance and accelerate early life immunity by acellular B. pertussis vaccines. In the present study, we optimized (a) the formulation delivery system, (b) structure, and (c) immunologic activity of novel small molecule imidazoquinoline TLR7/8 adjuvants towards human infant leukocytes, including dendritic cells. Upon immunization of neonatal mice, this TLR7/8 adjuvant overcame neonatal hyporesponsiveness to acellular pertussis vaccination by driving a T helper (Th)1/Th17 biased T cell- and IgG2c-skewed humoral response to a licensed acellular vaccine (DTaP). This potent immunization strategy may represent a new paradigm for effective immunization against pertussis and other pathogens in early life.

Reaction of SARS-CoV-2 antibodies with other pathogens, vaccines, and food antigens.

It has been shown that SARS-CoV-2 shares homology and cross-reacts with vaccines, other viruses, common bacteria and many human tissues. We were inspired by these findings, firstly, to investigate the reaction of SARS-CoV-2 monoclonal antibody with different pathogens and vaccines, particularly DTaP. Additionally, since our earlier studies have shown immune reactivity by antibodies made against pathogens and autoantigens towards different food antigens, we also studied cross-reaction between SARS-CoV-2 and common foods. For this, we reacted monoclonal and polyclonal antibodies against SARS-CoV-2 spike protein and nucleoprotein with 15 different bacterial and viral antigens and 2 different vaccines, BCG and DTaP, as well as with 180 different food peptides and proteins. The strongest reaction by SARS-CoV-2 antibodies were with DTaP vaccine antigen, E. faecalis, roasted almond, broccoli, soy, cashew, α+β casein and milk, pork, rice endochitinase, pineapple bromelain, and lentil lectin. Because the immune system tends to form immune responses towards the original version of an antigen that it has encountered, this cross-reactivity may have its advantages with regards to immunity against SARS-CoV-2, where the SARS-CoV-2 virus may elicit a “remembered” immune response because of its structural similarity to a pathogen or food antigen to which the immune system was previously exposed. Our findings indicate that cross-reactivity elicited by DTaP vaccines in combination with common herpesviruses, bacteria that are part of our normal flora such as E. faecalis, and foods that we consume on a daily basis should be investigated for possible cross-protection against COVID-19. Additional experiments would be needed to clarify whether or not this cross-protection is due to cross-reactive antibodies or long-term memory T and B cells in the blood.

CpG 1018® adjuvant enhances Tdap immune responses against Bordetella pertussis in mice

Bordetella pertussis is the causative agent of whooping cough (pertussis), a severe respiratory disease that can be fatal, particularly in infants. Despite high vaccine coverage, pertussis remains a problem because the currently used DTaP and Tdap vaccines do not completely prevent infection or transmission. It is well established that the alum adjuvant is a potential weakness of the acellular vaccines because the immunity provided by it is short-term. We aimed to evaluate the potential of CpG 1018® adjuvant to improve antibody responses and enhance protection against B. pertussis challenge in a murine model. A titrated range of Tdap vaccine doses were evaluated in order to best identify the adjuvant capability of CpG 1018. Antibody responses to pertussis toxin (PT), filamentous hemagglutinin (FHA), or the whole bacterium were increased due to the inclusion of CpG 1018. In B. pertussis intranasal challenge studies, we observed improved protection and bacterial clearance from the lower respiratory tract due to adding CpG 1018 to 1/20th the human dose of Tdap. Further, we determined that Tdap and Tdap + CpG 1018 were both capable of facilitating clearance of strains that do not express pertactin (PRN-), which are rising in prevalence. Functional phenotyping of antibodies revealed that the inclusion of CpG 1018 induced more bacterial opsonization and antibodies of the Th1 phenotype (IgG2a and IgG2b). This study demonstrates the potential of adding CpG 1018 to Tdap to improve immunogenicity and protection against B. pertussis compared to the conventional, alum-only adjuvanted Tdap vaccine.

DTaP vaccine

DTaP vaccine

Experts' Opinion for Improving Pertussis Vaccination Rates in Adolescents and Adults: A Call to Action.

This article highlights the importance of diphtheria-tetanus-acellular pertussis (with reduced antigen content, dTap) vaccination in preventing pertussis, a respiratory infection that is still widespread and easily transmitted. In particular, it highlights the need to receive a booster vaccination throughout life to maintain high antibody levels, which decrease through time. This document collects the opinions that emerged from the comparison between major Italian experts in the field of vaccination. This working group was created to promote a “call to action”, aimed at raising awareness among all institutions, public health authorities, and health workers involved in the vaccination process, about the importance of dTap vaccine administration and with the mindset of implementing the strategic vaccination plan provided by the National Vaccine Plan (NVP). In fact, despite this vaccine being included in the NVP, there are some issues attributable to the practice of vaccination (local health authorities, vaccination centers, occupational health services, gynecology centers, societies of work). Therefore, it is necessary that the Ministry defines the vaccination coverage objectives, identifies the groups of subjects who should receive the booster vaccine (subjects exposed to greater risk of infection, subjects over 60, pregnant women), and applies all the necessary measures to encourage the implementation of this practice.

DTaP vaccine

DTaP vaccine

Motivational interviewing and vaccine acceptance in children: The MOTIVE study

Background and ObjectiveVaccine coverage have been less than desired in young children in part due to parental vaccine hesitancy. Addressing health beliefs through patient-centered communication approaches such as motivational interviewing (MI) may improve vaccine confidence. Thus, the objective of this study was to determine the difference in paediatric vaccination coverage rates based on the Advisory Committee on Immunization Practices (ACIP) and Centers for Disease Control and Prevention (CDC) recommended schedule in children 0–6 years of age after an educational intervention for providers and integration of an MI-based communication tool, MOTIVE (MOtivational Interviewing Tool to Improve Vaccine AcceptancE). MethodsPaediatric and family practice providers in a federally qualified health center in the United States completed an educational intervention regarding vaccine hesitancy and use of the MOTIVE tool. Providers then implemented the MOTIVE tool to address common health beliefs using strong, presumptive vaccine recommendations and an MI framework during encounters with patients 0–6 years of age. Data were collected from 1-year pre-educational intervention (July 2018-June 2019, N = 2504) and post-intervention (July 2019-March 2020, N = 1954) to examine differences in vaccination coverage rates and documented vaccine refusals. ResultsUse of the MOTIVE tool was associated with a statistically significant increase in IIV vaccination coverage rate in children 6 months to 6 years of age (32.4% versus 43.9%, p < 0.01). A significantly increased Hib vaccination coverage rate was observed in children 0–18 months of age. Patients with commercial insurance also had significantly higher vaccination coverage rates for the DTaP, IPV, and VAR vaccines during the intervention period. Use of the MOTIVE tool was associated with a decrease in documented vaccine refusals per 100 patients in children 0–6 years of age (31.5 versus 17.6, p < 0.01). ConclusionUse of an MI-based communication tool may decrease vaccine refusals and improve childhood vaccination coverage rates, particularly for IIV.Clinical Trial Registration: ClinicalTrials.gov, NCT03934008, https://clinicaltrials.gov/ct2/show/NCT03934008, deidentified individual participant data will not be made available.

Pertussis

The bacterium Bordetella pertussis causes disease by producing various virulence and adhesion factors, among them pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN) and agglutinogens (Agg), also called fimbriae (FIM) "Typical" pertussis or whooping cough starts with unspecific respiratory symptoms (catarrhal phase) followed by severe coughing spasms with whoops and vomiting (paroxysmal phase) and only after weeks or months disease severity slowly wanes (convalescent phase). "Atypical pertussis" with unspecific, long-lasting coughing episodes is seen in adolescents and adults; very young infants may die from apnoea. B. pertussis is transmitted by droplets, and neither infection nor vaccination produce long lasting protection. Macrolide antibiotics are given to patients and their contacts to reduce spread of the organism; however, antibiotics do NOT change the duration or course of the disease once symptoms are present. Whole cell pertussis vaccines (wP) consist of whole inactivated B. pertussis-cells, whereas acellular vaccines (aP) consist of one to five single components like PT, FHA, PRN or FIM. Pertussis vaccines are currently only available as combination vaccines with tetanus und diphtheria (DTP). Among these are DTwP; DTaP; TdaP; and various DTP-combinations with Hib, IPV, HBV vaccines. Whole cell pertussis (DTwP) combination vaccines are more reactogenic, whereas DTaP vaccines are generally well tolerated. Some DTwP had good efficacy/effectiveness (90%), it was low (40%) with others. Vaccine efficacy of DTaP vaccines ranges between 70% and 90%. As with most vaccines, efficiency is higher for severe disease. While pertussis vaccines did control clinical disease, protection is limited. Vaccination is recommended for all infants (three doses) worldwide with a booster in the second year of life. Many countries give additional doses at school entry and in adolescents, and some to adults. Vaccination of pregnant women effectively protects newborn infants and is increasingly recommended.

Pertussis

The bacterium Bordetella pertussis causes disease by producing various virulence and adhesion factors, among them pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN) and agglutinogens (Agg), also called fimbriae (FIM) "Typical" pertussis or whooping cough starts with unspecific respiratory symptoms (catarrhal phase) followed by severe coughing spasms with whoops and vomiting (paroxysmal phase) and only after weeks or months disease severity slowly wanes (convalescent phase). "Atypical pertussis" with unspecific, long-lasting coughing episodes is seen in adolescents and adults; very young infants may die from apnoea. B. pertussis is transmitted by droplets, and neither infection nor vaccination produce long lasting protection. Macrolide antibiotics are given to patients and their contacts to reduce spread of the organism; however, antibiotics do NOT change the duration or course of the disease once symptoms are present. Whole cell pertussis vaccines (wP) consist of whole inactivated B. pertussis-cells, whereas acellular vaccines (aP) consist of one to five single components like PT, FHA, PRN or FIM. Pertussis vaccines are currently only available as combination vaccines with tetanus und diphtheria (DTP). Among these are DTwP; DTaP; TdaP; and various DTP-combinations with Hib, IPV, HBV vaccines. Whole cell pertussis (DTwP) combination vaccines are more reactogenic, whereas DTaP vaccines are generally well tolerated. Some DTwP had good efficacy/effectiveness (90%), it was low (40%) with others. Vaccine efficacy of DTaP vaccines ranges between 70% and 90%. As with most vaccines, efficiency is higher for severe disease. While pertussis vaccines did control clinical disease, protection is limited. Vaccination is recommended for all infants (three doses) worldwide with a booster in the second year of life. Many countries give additional doses at school entry and in adolescents, and some to adults. Vaccination of pregnant women effectively protects newborn infants and is increasingly recommended.

DTap vaccination uptake during pregnancy: Pregnant women-focused and health professionals-focused predictors in the Veneto Region (Italy)

BackgroundDespite recommendations, the uptake of dTap maternal vaccination is still low in many countries. The reasons for this must be investigated both on the patient’s and the healthcare professionals’ sides. MethodsA record linkage study was performed linking Birth Assitance Certificates and dTap mothers’ vaccination records (5183 deliveries) to describe the influence of socioeconomical and obstetrical-gynecological factors after the recommendations concerning dTap vaccination in pregnancy issued by the Italian Ministry of Health (August 2018). An interview was also administered to a subgroup of 656 new mothers on the occasion of the first vaccination of their newborns, in order to assess the dTap vaccination advice received from maternal care providers during pregnancy. A generalized linear model (binomial family, log link) was implemented to give a correct estimate of the mother’s relative risk of being vaccinated. ResultsSeveral pregnant women-focused factors are evident, but the most important ones are related to maternal care providers’ practices: after mutual adjustment, the explicit advice towards dTap maternal vaccination given by the Obstetrician-Gynecologist or the Midwife is associated with a 12-fold increase in the dTap coverage. ConclusionsMultiprofessional training is essential to make Obstetricians-Gynecologists and Midwives more confident in recommending dTaP maternal immunization.

Vaccination rates and determinants of nine recommended vaccines among migrants in China: a nationwide cross-sectional study

ABSTRACT In the past 70 years, in order to strengthen disease prevention and improve people’s health, China had introduced a series of vaccine policies. However, compared with the permanent population, studies on the vaccination situation of the migrants were lacking. This study aimed to evaluate the vaccination rates of nine recommended vaccines (HepB, HepA, FIn, DTaP, JE, Rab, MPSV, HF, and TIG vaccine) among migrants and related determinants. We used nationwide data from the 2017 Migrant Population Dynamic Monitoring Survey (MDMS) to analyze the vaccination rates of migrants in terms of gender, age, marital status, household registration, education, health level, etc. The total vaccination rate of nine recommended vaccines was 64.8% (6488/10013). Education level and health level were positively correlated with vaccination rates, but age was negatively correlated with vaccination rates. Migrants from urban regions had a higher vaccination rate than those from rural regions. Among the nine recommended vaccines, HepB vaccination rate was the highest (59.08%), while HF vaccination rate was the lowest (4.08%). Combined with policies and demographic characteristics, the relationship between age, household registration, health level, education level and vaccination were studied. The findings suggested that more attention should be given to vaccination of migrants, and the monitoring of vaccination of such groups should be strengthened through information technology.

Innovation of Shallot (Allium Ascalonicum L) Essential Oil for Fever Reduction in Infants Post DTaP Immunization

DTaP vaccination causes an increased body temperature or fever in most infants. There are pharmacological or non-pharmacological efforts to reduce fever in infants post-DTaP immunization. In addition, shallots are a family medicinal plant in Indonesia commonly used to reduce fever. There should be innovation in the dosage form of shallots so their use is more effective and efficient. This study analyzes the effect of shallot essential oil on fever reduction in infants post-DTaP vaccination. It was a quasi-experimental research design, with one group pre and post-test design. The population of this research was all infants aged 1-12 months who were enrolled in the infant cohort in 2020 at Independent Midwifery Practice (IMP) Istiqomah from May to August 2020. Meanwhile, there were 20 samples by accidental sampling. The research instruments were shallot extract oil, a digital thermometer, and an observation sheet. The data analysis used the Repeated Measures Anova test. The results showed that the mean body temperature before immunization was 36.57 degrees Celcius, while after the experiment was 36.9 degrees Celcius. The statistical test results value ρ = 0.000. There was a significant difference in the mean body temperature from time to time in infants with shallot essential oil administration. This study concludes that shallot essential oil reduces fever in infants post-DTaP immunization. Further research should use a control group, more significant samples, and inclusion criteria limitation.

Estimating Population-Level Effects of the Acellular Pertussis Vaccine Using Routinely Collected Immunization Data.

Measuring and reporting the different population-level effects of the acellular pertussis vaccine on pertussis disease in addition to direct effects can increase the cost-effectiveness of a vaccine. We conducted a retrospective cohort study of children born between 1 January 2008 and 31 December 2017, in King County, Washington, who were enrolled in the Washington State Immunization Information System. Diphtheria, tetanus toxoids, and acellular pertussis (DTaP) vaccination data from in the Washington State Immunization Information System was linked with pertussis case data from Public Health Seattle and King County. Census-level vaccination coverage was estimated as proportion of age-appropriately vaccinated children residing in it. Direct vaccine effectiveness was estimated by comparing pertussis risk in fully vaccinated and undervaccinated children. Population-level vaccine effectiveness (VE) measures were estimated by comparing pertussis risk in census tracts in the highest quartile for vaccination coverage with that in the lowest quartile. For direct protection, estimated VE was 76% (95% confidence interval, 63%-84%) in low-vaccination-coverage clusters, and it decreased to 47% (13%-68%) in high-coverage clusters, after adjustment for potential confounders. The estimated indirect VE was 45.0% (95% confidence interval, 1%-70%), the total VE 93.9% (91%-96%), and the overall VE 42.2% (19%-60%). Our findings suggest that DTaP vaccination provided direct as well as indirect protection in the highly immunized King County, Washington. Routine DTaP vaccination programs may have the potential to provide not only protection for vaccinated individuals but also for the undervaccinated individuals living in the same area.

Immunization crisis may develop due to economic crisis during COVID-19 pandemic

Dear Editor,&#x0D; COVID-19 pandemic is a global health crisis with 61, 149,391 confirmed cases and 370,478 deaths till 29May, 2020 [1]. This pandemic has shattered many economies with an estimated loss of $5.8 trillion to $8.8 trillion globally. This economic loss can result in reduction in funds to World Health Organization. Unfortunately, United States of America (USA) has announced termination of any further funding to WHO which can lead to another global health crisis [2]. As WHO is a voluntary funding based organization its main donor are America, China, Japan, Germany and United Kingdom. Among these USA is the main donor with a contribution of $115.8million alone followed by China $57.4 million, Japan $41million, Germany $29.1 million and UK $21.9 million [3]. America’s termination of funding can put WHO and child health programs in serious crisis.&#x0D; Among many programs run by WHO one of the most important program is immunization of children. Immunization coverage programs save 2-3 million lives per year causing decline in measles related deaths, eradication of polio, surveillance of rotavirus, BCG and DTaP vaccination in children[4]. It is estimated that during Millennium Development Goal (MDG) there is overall decline in child related mortalities due to malaria, measles, diarrhea, AIDS and meningitis [5]. Remarkable results are achieved with measles are diarrhea immunization programs causing a decline in death rate by 73% and 80% respectively. According to a study with current success rate diarrhea related deaths can be virtually eliminated by 2030. Another successful program is “End Polio” program which eradicated polio from world except from Pakistan and Afghanistan [4][6]. This termination of funds to WHO can waste all previous efforts in developing countries.&#x0D; On the other hand despite of all efforts still 19.4 million children did not received prescribed dose of vaccines. Data analysis revealed among these 60% of children belong to 10 developing countries namely Angola, Brazil, the Democratic Republic of the Congo, Ethiopia, India, Indonesia, Nigeria, Pakistan, the Philippines and Viet Nam [4]. These countries mainly rely on foreign funding and Non-Government Organization (NGOs) for child health care programs.&#x0D; According to WHO immunization coverage report updated on 6 December 2019 globally 100% results were not achieved Fig 1. The immunization rate was low in developing counties with high population density and poor health care facilities. People are already battling to fulfill basic necessities like food, clean drinking water and shelter [7].&#x0D; COVID-19 pandemic has further worsened the economies of these counties. As a result these counties will not be able to support vaccination programs at their own. WHO has an already established network in these regions, any efforts from scratch will waste lots of time and eventually cost millions of lives. Now a heavy responsibility lies on the shoulders of world leaders to foresee this up-coming crisis and take appropriate measures. Timely management of funds by convincing USA government or by alternative funding sources can save work of decades done by global community through WHO in saving lives in developing countries.

Article of Significant Interest in This Issue

DTaP and Tdap vaccines have been utilized for prevention of diphtheria, tetanus, and pertussis in the United States since 1996 and 2005, respectively. However, the protective immunity that these vaccines provide is not long-term, and the disease is re-emerging. DTaP and Tdap are administered by intramuscular injection to induce systemic humoral immunity. In this study, Wolf et al. (e00607-20) investigate mucosal immunization through intranasal administration. A murine model was used to study short- and long-term protection elicited after intranasal vaccination. Nasal immunization provided long-term protection, especially when whole beta-glucan and alum adjuvants were used to induce local and systemic humoral immune responses persisting out to 6 months postboost immunization.

Young Infants’ Exposure to Organophosphate Esters and Associations with Vaccination Responses

Background: Organophosphate esters (OPEs) are applied as flame retardants and plasticizers to many consumer items such as home furnishings and children’s products. Little is known about OPE exposure among infants, who are a vulnerable population due to their rapid development. Methods: We collected spot urine samples from 6-week-old (n=100) and 12-month-old infants (n=63), with about half of the infants evaluated at both ages (n=52), to characterize OPE exposure and assess factors contributing to higher exposures. In addition, we evaluated serum for tetanus and diphtheria antibody titers at 12 months (n=93; among children receiving the DTaP vaccine). Results: Five of six OPE urinary metabolites analyzed were detected frequently (&gt;70%). Diphenyl phosphate was detected in every urine sample, while bis(2-chloro-isopropyl) phosphate (BCIPP) was the most abundant metabolite measured overall. Concentrations of BCIPP and a second tris(2-chloroisopropyl) phosphate (TCIPP) metabolite, BCIPHIPP, were significantly greater among 6-week-olds compared to 12-month-olds (p&lt;0.0001). Levels of other OPE metabolites were not statistically different in the first year of life. Infants who were currently breastfed had higher levels of TCIPP metabolites in their urine, with BCIPP levels 6.2 times higher at 6 weeks and BCIPHIPP 2.2 times higher at 12 months (10β=7.2; 95% CI: 1.6-32.1 and 10β=3.2; 95% CI: 1.2-8.1, respectively). After adjusting for demographics and breastfeeding status, each log10-increase in BCIPP concentrations was associated with a 0.5 IU/mL decrease in tetanus antibodies (p=0.05); a similar association was observed for urinary BDCIPP with diphtheria titers. Urinary BCIPP at 6-weeks was also associated with increased reports of respiratory infections within the first year of life (OR: 4.1, CI: 0.9-18, p=0.06); increased exposures to other OPEs were associated with decreased allergy reports. Conclusions: Cumulatively, results suggest levels of OPE exposure are higher for infants than older children, and these increased exposures could be associated with indicators of adverse immune function.

Timeliness of DTaP-IPV-Hib Vaccination and Development of Atopic Dermatitis Between 4 Months and 1 Year of Age—Register-Based Cohort Study

An Australian study including 4433 children found that delayed Diphtheria-Tetanus-acellular Pertussis-containing vaccination was associated with reduced risk of developing atopic dermatitis (AD) before age 1 year. We assessed whether delayed vaccination against diphtheria, tetanus, acellular pertussis, polio, and Haemophilus influenzae type b (Diphtheria, Tetanus, acellular Pertussis - Inactivated Polio vaccine - Haemophilus influenzae type b [DTaP]) was associated with a reduced risk of new cases of AD before age 1 year in Denmark. We used nationwide registers to follow 883,160 children born in Denmark from 1997 to 2012. Binary regression models adjusting for potential confounding factors were applied to estimate relative risks (adjusted relative risks [aRRs]) of developing AD among children with delayed DTaP vaccination (defined as given 1 month or more after the recommended age) compared with timely vaccinated children. Among 143,429 children with a delayed first dose of DTaP, 4,847 (3.4%) developed AD between age 4 months and 1 year, compared with 27,628 (3.7%) among 739,731 children not having delayed DTaP (aRR 0.94; 95% CI, 0.91-0.97). The aRR was 0.94 (95% CI, 0.90-0.99) for children with a delayed second dose, and the aRR was 0.88 (95% CI, 0.82-0.93) when comparing children with delayed first and second doses with all timely vaccinated children. The results support the hypothesis that delayed vaccination with DTaP is associated with reduced risk of developing new cases of AD after age 4 months. The dose-dependent relationship strengthens the evidence of a causal relationship. Some countries are introducing maternal pertussis vaccination and delaying the first dose of DTaP, providing a possibility for further testing the hypothesis.

Vaccination and immunization status among healthcare students: results from the SAVES survey

Abstract Background Adequate vaccination coverage among healthcare workers, including students in healthcare professions (SHPs), is crucial in order to prevent spreading of infections within healthcare facilities. However, vaccination coverage among SHPs is often inadequate. We aimed to describe the vaccination/immunization status of SHPs of the University of Milan. Methods We spread an e-survey to the academic e-mail addresses of postgraduate medical residents and to first- and last-year undergraduate SHPs. The questionnaire covered sociodemographic data (age, sex, education, municipality of residence, internship in high-risk wards) and the reported vaccination/immunization status for Influenza (previous flu season), Varicella, MPR and DTaP vaccines. Results Among 5743 invited SHPs, 884 participated in the survey. The study sample comprised 462 medical residents and 422 undergraduate SHPs (medicine 176, nursery 186, midwifery 4, healthcare assistance 32, prevention techniques 24). Median age was 27 years (IQR 7); 68.4% participants were female; 91.3% had attended high school in a lyceum, while others in a professional (2.9%) or technical (5.8%) institute; 36.7% lived in municipalities of &amp;lt; 20.000 inhabitants, while 26.1% of &amp;gt; 250.000. Traineeships took place in high-risk wards for 46% of participants. Reported vaccination coverage for Influenza was 33,7% (with higher coverage for pediatric nursing and midwifery students, medicine students and medical residents). Participants reported immunity (either vaccine or natural immunity) to Varicella in 93,3% cases. Declared vaccination coverage for Hepatitis B was 94,1%; 91,7% participants reportedly completed the MPR schedule, 76,2% the recommended DTaP booster. Conclusions Influenza vaccination coverage was suboptimal in our sample of SHPs, suggesting the need of specific educational programs and targeted vaccination campaigns, which may help shaping a positive vaccination attitude for future healthcare professionals. Key messages Immunization status for VPDs is suboptimal among Italian students in healthcare professions. The monitoring of the immunization status should include healthcare students actively involved in healthcare activities.

Seizures not increased with DTaP, PCV and Hib vaccine coadministration

Seizures not increased with DTaP, PCV and Hib vaccine coadministration

Results from Melanoma Antigen Redirected Vaccine Stimulated Autologous Lymphocytes (MARVSmALo): A pilot study.

e15026 Background: Despite improvements in treatment with targeted agents and immunotherapeutics metastatic melanoma still has a guarded prognosis. Many melanoma cells upregulate the disialoganglioside GD2. Early GD2 chimeric antigen receptor (CAR) T-cell studies in neuroblastoma demonstrated no toxicity but limited ability to expand in vivo. Strategies to expand these GD2.CAR T cells might improve efficacy while retaining safety. This pilot study aimed to evaluate the safety and efficacy of first generation 14g2a.zeta chimeric antigen receptor ( GD2.CAR ) transduced, activated T cells enriched for vaccine specific cytotoxic T-Lymphocytes (tvs-CTL). Methods: Patients with metastatic melanoma in which standard therapy had failed were eligible if they had recovered from effects of prior therapy, did not have rapidly progressive disease, were free of melanoma involving the CNS and did not have a contraindication to receiving Hepatitis B, Polio or DTAP vaccine. Patients received each of these vaccines prior to cell harvest, 4 days before and 28 days after autologous T cell infusion. Patient 1 was treated with 2 x 108 cell dose and patients 2 and 3 were treated with 4x108 cell dose. We used QPCR to measure transgene copy number in patients before and after infusion. Interferon-gamma enzyme linked immunospot (ELISPOT) assay was used to measure the frequencies of tetanus, pertussis, diphtheria, poliovirus and tumor antigens-specific T cells in peripheral blood. Results: GD2.CAR-tvs-CTL were manufactured and infused in 3 patients. Overall the infusions were safe. Seven low grade adverse events possibly related to study participation were reported. The first 2 patients did not demonstrate robust in vivo expansion of GD2.CAR-tvs-CTLs by QPCR and had rapid disease progression. In patient 3 a significant expansion of GD2.CAR-tvs-CTLs, i.e. 18,250 copies/ug genomic DNA was observed on day 7 and cells persisted at 159 copies/ug DNA for up to 12 months (latest measured time point). High pertussis-specific responses were also observed by INF-gamma ELISPOT in this patient starting from day 14 after the vaccination through month 12. Conclusions: We have demonstrated that GD2.CAR T cells expanded and persisted in melanoma patient for up to 12 months. The use of vaccination before blood procurement for T cell manufacture and boosting virus-specific T cell after CAR T cell infusion is a safe strategy and may have helped induced higher transgene levels in one of three patients. Clinical trial information: NCT02482532 .