Multiphoton high-resolution 3D imaging of Langerhans cells and keratinocytes in the mouse skin model adopted for epidermal powdered immunization

Langerhans cells (LCs) can be targeted with DNA-coated gold micro-projectiles ("Gene Gun") to induce potent cellular and humoral immune responses. It is likely that the relative volumetric distribution of LCs and keratinocytes within the epidermis impacts on the efficacy of Gene Gun immunization protocols. This study quantified the three-dimensional (3D) distribution of LCs and keratinocytes in the mouse skin model with a near-infrared multiphoton laser-scanning microscope (NIR-MPLSM). Stratum corneum (SC) and viable epidermal thickness measured with MPLSM was found in close agreement with conventional histology. LCs were located in the vertical plane at a mean depth of 14.9 mum, less than 3 mum above the dermo-epidermal boundary and with a normal histogram distribution. This likely corresponds to the fact that LCs reside in the suprabasal layer (stratum germinativum). The nuclear volume of keratinocytes was found to be approximately 1.4 times larger than that of resident LCs (88.6 mum3). Importantly, the ratio of LCs to keratinocytes in mouse ear skin (1:15) is more than three times higher than that reported for human breast skin (1:53). Accordingly, cross-presentation may be more significant in clinical Gene Gun applications than in pre-clinical mouse studies. These interspecies differences should be considered in pre-clinical trials using mouse models.

Molecular investigations into vaginal immunization with HIV gp41 antigenic construct H4A in a quick release solid dosage form

A robust vaginal immune response is considered essential for an effective prophylactic vaccine that prevents transmission of HIV and other sexually acquired diseases. Considerable attention has recently focused on the potential of vaginally administered vaccines as a means to induce such local immunity. However, the potential for vaccination at this site remains in doubt as the vaginal mucosa is generally considered to have low immune inductive potential. In the current study, we explored for the first time the use of a quick release, freeze-dried, solid dosage system for practical vaginal administration of a protein antigen. These solid dosage forms overcome the common problem associated with leakage and poor retention of vaginally administered antigen solutions. Mice were immunized vaginally with H4A, an HIV gp41 envelope based recombinant protein, using quick release, freeze-dried solid rods, and the immune responses compared to a control group immunized via subcutaneous H4A injection. Vaginally immunized mice failed to elicit robust immune responses. Our detailed investigations, involving cytokine analysis, the stability of H4A in mouse cervicovaginal lavage, and elucidation of the state of H4A protein in the immediate-release dosage form, revealed that antigen instability in vaginal fluid, the state of the antigen in the dosage form, and the cytokine profile induced are all likely to have contributed to the observed lack of immunogenicity. These are important factors affecting vaginal immunization and provide a rational basis for explaining the typically poor and variable elicitation of immunity at this site, despite the presence of immune responsive cells within the vaginal mucosae. In future mucosal vaccine studies, a more explicit focus on antigen stability in the dosage form and the immune potential of available antigen-responsive cells is recommended.

Development and evaluation of a novel intranasal spray for the delivery of amantadine

The aim of this study was to develop and characterize an intranasal delivery system for amantadine hydrochloride (AMT). Optimal formulations consisted of a thermosensitive polymer Pluronic® 127 and either carboxymethyl cellulose or chitosan which demonstrated gel transition at nasal cavity temperatures (34 ± 1°C). Rheologically, the loss tangent (Tan δ) confirmed a 3-stage gelation phenomena at 34 ± 1°C and non-Newtonian behavior. Storage of optimized formulation carboxymethyl cellulose and optimal formulation chitosan at 4°C for 8 weeks resulted in repeatable release profiles at 34°C when sampled, with a Fickian mechanism earlier on but moving toward anomalous transport by week 8. Polymers (Pluronic® 127, carboxymethyl cellulose, and chitosan) demonstrated no significant cellular toxicity to human nasal epithelial cells up to 4 mg/mL and up to 1 mM for AMT (IC50: 4.5 ± 0.05 mM). Optimized formulation carboxymethyl cellulose and optimal formulation chitosan demonstrated slower release across an in vitro human nasal airway model (43%-44% vs 79 ± 4.58% for AMT). Using a human nasal cast model, deposition into the olfactory regions (potential nose-to-brain) was demonstrated on nozzle insertion (5 mm), whereas tilting of the head forward (15°) resulted in greater deposition in the bulk of the nasal cavity.

Role of the transgenic human thyrotropin receptor A-subunit in thyroiditis induced by A-subunit immunization and regulatory T cell depletion

Transgenic BALB/c mice that express intrathyroidal human thyroid stimulating hormone receptor (TSHR) A-subunit, unlike wild-type (WT) littermates, develop thyroid lymphocytic infiltration and spreading to other thyroid autoantigens after T regulatory cell (Treg) depletion and immunization with human thyrotropin receptor (hTSHR) adenovirus. To determine if this process involves intramolecular epitope spreading, we studied antibody and T cell recognition of TSHR ectodomain peptides (A–Z). In transgenic and WT mice, regardless of Treg depletion, TSHR antibodies bound predominantly to N-terminal peptide A and much less to a few downstream peptides. After Treg depletion, splenocytes from WT mice responded to peptides C, D and J (all in the A-subunit), but transgenic splenocytes recognized only peptide D. Because CD4+ T cells are critical for thyroid lymphocytic infiltration, amino acid sequences of these peptides were examined for in silico binding to BALB/c major histocompatibility complex class II (IA–d). High affinity subsequences (inhibitory concentration of 50% < 50 nm) are present in peptides C and D (not J) of the hTSHR and mouse TSHR equivalents. These data probably explain why transgenic splenocytes do not recognize peptide J. Mouse TSHR mRNA levels are comparable in transgenic and WT thyroids, but only transgenics have human A-subunit mRNA. Transgenic mice can present mouse TSHR and human A-subunit-derived peptides. However, WT mice can present only mouse TSHR, and two to four amino acid species differences may preclude recognition by CD4+ T cells activated by hTSHR-adenovirus. Overall, thyroid lymphocytic infiltration in the transgenic mice is unrelated to epitopic spreading but involves human A-subunit peptides for recognition by T cells activated using the hTSHR.

Immunization and targeted destruction of networks using explosive percolation

7 pages, 6 figures

Digital Epidemiology Reveals Global Childhood Disease Seasonality and the Effects of Immunization

ACKNOWLEDGMENTS. We would like to thank Fernando Gonzalez-Dominguez and Gilberto Vaughan for providing the chicken pox case reports from Mexico, and the Estonia Health Board, Department of Communicable Disease Surveillance and Control, for Estonian chicken pox case reports. KB would like to thank Mercedes Pascual, her lab, and Marisa Eisenberg for helpful comments. Jesus Cantu (research assistant, Princeton University) translated and categorized chicken pox searches from Mexico, Thailand, Australia, and the US.

Development and testing of an analytical framework for immunization program planning in Canada

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Development and testing of an analytical framework for immunization program planning in Canada

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Iowa Immunization Program Annual Report 2013, April 30, 2014

The Bureau of Immunization is part of the Division of Acute Disease Prevention and Emergency Response (ADPER) at the Iowa Department of Public Health (IDPH). The ADPER division provides support, technical assistance and consultation to local hospitals, public health agencies, community health centers, emergency medical service programs and local health care providers regarding infectious diseases, disease prevention and control, injury prevention and public health and health care emergency preparedness and response. The division encompasses the Center for Acute Disease Epidemiology (CADE), the Bureau of Immunization and Tuberculosis (ITB), the Bureau of Emergency Medical Services (EMS), the Bureau of Communication and Planning (CAP), the Office of Health Information Technology (HIT), and the Center for Disaster Operations and Response (CDOR). The Bureau of Immunization and Tuberculosis includes the Immunization Program, the Tuberculosis Control Program, and the Refugee Health Program. The mission of the Immunization Program is to decrease vaccine‐preventable diseases through education, advocacy and partnership. While there has been major advancement in expanding immunizations to many parts of Iowa’s population, work must continue with public and private health care providers to promote the program’s vision of healthy Iowans living in communities free of vaccine‐preventable diseases. Accomplishing this goal will require achieving and maintaining high vaccination coverage levels, improving vaccination strategies among under‐vaccinated populations, prompt reporting and thorough investigation of suspected disease cases, and rapid institution of control measures. The Immunization Program is comprised of multiple programs that provide immunization services throughout the state: Adolescent Immunization Program, Adult Immunization Program, Immunization Registry Information System (IRIS), Vaccines for Children Program (VFC), Perinatal Hepatitis B Program, and Immunization Assessment Program.

South Carolina Immunization Fact Sheet

This paper gives statistics on the immunization of children and adolescents in South Carolina.

Factors Influencing Children’s Full Immunization in Ethiopia

Child morbidity and mortality in Ethiopia is mainly due to vaccine preventable diseases. Although numerous interventions have been made since the 1980’s to increase vaccination coverage, the level of full immunization is low in the country. This study examines factors influencing children’s full immunization based on data on 1927 children aged 12-23 months extracted from the 2011 Ethiopian Demographic and Health Survey. Multinomial logistic regression model was fitted to identify predictors of full immunization. The result shows that only 24.3% of the children were fully immunized. There was significant difference between regions in immunization coverage in which Tigray, Dire Dawa, and Addis Ababa performed well. In Oromia, Afar, Somali, Benishangul-Gumuz, and Gambela regions, the likelihood of children’s full immunization was significantly lower. Children born to mothers living in households with better socio-economic status, with frequent access to media, and who visit health facilities for antenatal care were more likely to be fully immunized. The results imply the importance of narrowing regional differences, improving women’s socio-economic status and utilization of antenatal care services, and strengthening culture-sensitive media campaign as a means of achieving full immunization of all children

Nanopartículas poliméricas de administración intranasal para la liberación de activos en el sistema nervioso central

Objetivos: Analizar la situación actual de las investigaciones relacionadas con las nanopartículas poliméricas como sistemas de liberación de fármacos, así como los estudios que muestran las aplicaciones de fármacos incorporados en dichos sistemas y liberados en el sistema nervioso central mediante la administración intranasal. Métodos: Se utilizó, entre otras, como principal fuente la base de datos de la National Library of Medicine, Washington, DC (MEDLINE: PubMed) para realizar la búsqueda de artículos de investigación más importantes publicados sobre el tema. Resultados: Muchos de los fármacos utilizados para el tratamiento de enfermedades neurodegenerativas no son capaces de atravesar la barrera hematoencefálica (BHE) y llegar al cerebro en concentraciones suficientes para ejercer su efecto terapéutico. Es por ello que surge la idea de desarrollar nanopartículas poliméricas para ser administradas por vía nasal. Gracias a la utilización de dichos sistemas, numerosos estudios han puesto de manifiesto una mejora en la utilidad clínica del fármaco, permitiendo reducir la dosis y la frecuencia de dosificación a la vez que se reducen los efectos secundarios. Conclusiones: Pese a los avances realizados, demostrándose un aumento de la concentración de fármacos incorporados en sistemas nanoparticulados que llegan al cerebro, aún son necesarias investigaciones que solventen los problemas de toxicidad presentados por estos sistemas y su variabilidad de dosis absorbida.

Factors affecting vaccine handling and storage practices among immunization service providers in Ibadan, Oyo State, Nigeria.

Background: Improper handling has been identified as one of the major reasons for the decline in vaccine potency at the time of administration. Loss of potency becomes evident when immunised individuals contract the diseases the vaccines were meant to prevent. Objective: Assessing the factors associated with vaccine handling and storage practices. Methods: This was a cross-sectional study. Three-stage sampling was used to recruit 380 vaccine handlers from 273 health facilities from 11 Local Government areas in Ibadan. Data was analysed using SPSS version 16 Results: Seventy-three percent were aware of vaccine handling and storage guidelines with 68.4% having ever read such guidelines. Only 15.3% read a guideline less than 1 month prior to the study. About 65.0% had received training on vaccine management. Incorrect handling practices reported included storing injections with vaccines (13.7%) and maintaining vaccine temperature using ice blocks (7.6%). About 43.0% had good knowledge of vaccine management, while 66.1% had good vaccine management practices. Respondents who had good knowledge of vaccine handling and storage [OR=10.0, 95%CI (5.28 – 18.94), p < 0.001] and had received formal training on vaccine management [OR=5.3, 95%CI (2.50 – 11.14), p< 0.001] were more likely to have good vaccine handling and storage practices. Conclusion: Regular training is recommended to enhance vaccine handling and storage practices.