Foreign and domestic researches reveal that influenza vaccine is safe and can effectively reduce related healthy trouble caused by influenza in the elderly, infant and high-risk population, etc. The main purpose of ¡§Influenza vaccine policy¡¨ is public service. To promote concepts of citizenism and consumer-right brings the concept of marketing. With the progress of democratic trend, when policies are discussed, planned, established and executed, the government should consider policies as ¡§products¡¨ to sale and emphasize policy-marketing concept to gain public approval and acceptance. This study was based on influenza vaccine policy carried out by Centers for Disease Control, R.O.C. (Taiwan). In accordance with the marketing framework of public policy advocated by Snavely (1991), we designed a questionnaire investigation on surveying citizen and medical staff of Kaoshiung to see if government vaccine policies can grasp the important path as well as positive effectiveness of policy marketing, and issued our research outcomes on promoting prevention and cure of vaccine to be part of references for government health center. The results of descriptive statistics displayed that 80% of survey candidates regardless of common people or medical practitioners possessing professional knowledge agreed that influenza vaccine was an outstanding policy and approved the government¡¦s response and clarification in facing medial negative report. 60% of survey candidates were affected and worried about safety of influenza vaccine, after receiving these medial negative reports. Former experience of vaccination would considerably affect the willingness of general public to receive a flu shot. Survey candidates mainly received information about influenza vaccine from television media and preferred to approve either experts or endorsers. Results of Chi-square test showed that there was a significant correlation between ¡§influenza vaccination¡¨ and common people¡¦s experience of suffering from chronic disease or unhealthy inoculable response. Results of independent-samples T test and one-way ANOVA indicated the factors correlating significantly with the analytic variables of approval of degree ¡§service¡¨ in marketing mix program. In the case of common people, these factors included the following variables such as ¡§those who had ever been vaccinated¡¨, ¡§those who had ever been vaccinated and suffered from bad inculable response¡¨, and ¡§those who had ever participated health education during the past year¡¨. In respect of medical practitioners, these factors included the following variables such as ¡§those who had ever been vaccinated and suffered from bad inculable response¡¨ and ¡§those who had ever taken the thematic speech, related websites or webpages¡¨. With regard to analytic variables of approval of degree ¡§cost¡¨ in marketing mix program included following factors. For common people, the factors contained ¡§those who had ever been vaccinated and suffered from bad inculable response¡¨, and ¡§those who had ever participated health education, related bulletin board and scrolling text marquee during the past year¡¨. For medical practitioners, the factors comprised ¡§those who had ever been vaccinated and suffered from bad inculable response¡¨ and ¡§those who had ever taken thematic speech, related vedio, websites or webpages¡¨ As for analytic variables of approval of degree ¡§supply of information and education¡¨ in marketing mix program included following factors. For common people, the factors contained ¡§those who had ever been vaccinated¡¨, and ¡§those who had ever participated related bulletin board, scrolling text marquee, thematic speech, TV vedio, broadcasts, websites or webpages during the past year¡¨. For medical practitioners, the factors comprised ¡§occupation¡¨ and ¡§those who had ever perused related books, journals, newspaper, websites or webpages¡¨. Policy marketing concept should not be neglected in the application of executing public policy. For influenza vaccination policy marketing, first of all, public mental barriers of safety of influenza vaccine must be overcome, therefore the most critical issue is to enhance advertisement and education about safety of vaccine in order to improve confidence of public for influenza vaccine and to prevent from the loophole of influenza prophylaxis and treatment. This study suggests that we must to adopt consumer-driven marketing concept for the influenza vaccine policy marketing mix program. Government public relations should establish harmonious media relations and use higher acceptance of promotion way to focus on the limited resources to target market. We should make concise and rememberable messages and integration marketing communication way to achieve the comprehensive effect. We expect that the government performs policy marketing to promote the public approval of ¡§influenza vaccine policy¡¨ and to raise influenza vaccination rate on diminishing influenza morbidity and mortality rate.

Abstract Safety assessment relating to the presence of impurities, residual materials and contaminants in vaccines is a focus area of research at the United States Food and Drug Administration (FDA). Sponsors who submit Investigational New Drug (IND) applications for new vaccine products must report the results of safety assessments to the Division of Vaccines and Related Products Applications (DVRPA). Scientifically defining thresholds of toxicological concern (TTCs) as they apply to vaccine constituents will provide a useful aid to the sponsors and public regarding safety assessments of compounds for which there is little or no toxicity data. TTCs are mathematically modeled and extrapolated levels, below which adverse human health effects are not expected to occur (Kroes, 2004). In this project, we accessed DVRPA's submission databases and open source data to yield an initial chemical test set. Using INCHEM, RepDose, RTECS and TOXNET, we gathered LD50 and TDLo data. Using a structure-based decision tree, provided in the ToxTree software package, (3) different algorithms (The Cramer extended, the In vivo rodent micronucleus assay, and the Benigni-Bossa rule base for carcinogenicity by ISS) were applied to assign the initial test set (n= 197) of chemicals into structural families based on structural alerts (SAs). This resulted in six (6) potential methods for elucidating TTCs: In vivo rodent micronucleus assay/ LD50, Benigni-Bossa/ LD50, Cramer extended/ LD50, In vivo rodent micronucleus assay/ TDLo, Benigni-Bossa/ TDLo, and the Cramer extended/ TDLo. After each algorithm designated two structural families each, the distribution of TDLo's and LD50's for each structural family was subjected to a preliminary data analysis using JMP statistical software version 9. Based on an analysis of quantiles, skew, and kurtosis, it was concluded that the TDLo dataset was of poor quality and was dropped from further analysis, and that the In vivo rodent micronucleus assay algorithm failed to partition the initial test set in a meaningful way, so it too was culled from further consideration. This resulted in (2) remaining TTC methods for further consideration: Benigni-Bossa/ LD50 and the Cramer extended/ LD50. The remaining methods were subjected to internal validation based on Gene-Tox, CCRIS, CPDB, IARC, and EPA classaifications for genotoxic mutagenicity and carcinogenicity. Validation parameters were calculated for both methods and it was determined that the Benigni-Bossa/ LD50 method outperformed the Cramer extended/ LD50 method in terms of specificity (87.2 vs. 48.1%#37;), accuracy (65.2 vs. 52.94%#37;), positive predictivity (66.6 vs. 50%#37;), negative predictivity (64.8 vs. 56.5%#37;), ROC+ (2 vs. 1) and ROC- (1.84 vs. 1.3). These results indicated that the Benigni-Bossa/ LD50 was the most appropriate for calculating TTCs for vaccine constituents. For each class, the lower 2.5th percentile LD50 was extrapolated to a TTC value using safety estimates derived using uncertainty factors (UF) and adjusting for adult human weight. Final TTCs were designated as 18.06 μg/ person and 20.616 μg/ person for the Benigni-Bossa positive and negative structural families.

<p>The prevalence of allergic disease such as peanut (PN) allergy has increased within the last century. Environmental factors have been associated with an increased risk of developing allergic diseases. The severity of allergic diseases has also increased and clinical trials are investigating allergen-specific immunotherapy as a method to treat allergies. The purpose of this work was to identify a vaccine adjuvant that induced potent antigen-specific Th1 immune responses and determine its ability to reduce the development and severity of Th2- mediated allergic disease, using models of peanut hypersensitivity.</p><p>Three studies were performed. The first study compared a variety of vaccine adjuvants to identify a potent adjuvant with strong Th1-associated activity. This study verified that the Toll-like receptor (TLR) ligand CpG could induce potent Th1-associated immune responses. The second study tested the ability of environmental endotoxin levels and alum-adjuvanted vaccines to modulate the development of allergic disease using a mouse model of peanut allergy. Additionally, the TLR ligands, CpG and MPL, were combined with alum-adjuvanted vaccines to determine their ability to further impact allergic disease development. Results suggested that the addition of CpG to an alum-adjuvanted vaccine indirectly modified host immunity in a manner that decreased the development of PN-induced allergic disease. The last study evaluated the ability of CpG to reduce the severity of peanut allergy symptoms when combined with peanut in an immunotherapy formulation administered to peanut-hypersensitive mice. Nasal immunotherapy with PN + CpG but not PN alone or CpG alone reduced the severity of PN-induced anaphylaxis in hypersensitive mice. PN-hypersensitive mice treated with PN + CpG displayed an increased PN-specific IgG2c and IFN-γ responses. A reduction in allergic disease severity in PN-hypersensitive mice correlated with an increase in PN-specific IgG2c, IFN-γ and IL-10 responses and a reduction in PN-specific IL-13 responses, suggesting a shift from Th2 responses towards Th1 and/or T regulatory cell responses.</p><p>Taken together, the data obtained from these studies demonstrate the potent activity of CpG to induce antigen-specific Th1-associated immune responses and also reduce the severity of peanut-hypersensitivity in mice through direct and indirect association with peanut allergens.</p> / Dissertation

Delivery of medicinal products to specific targets can be aided by utilizing different routes of administration. Particular routes may be advantageous when delivering products designed for therapeutic drug delivery, gene therapy, or vaccination. Vaccine candidates must remain stable, be delivered to their proper compartments, and promote sufficient immune responses to their delivered antigens, properties that can be modulated by formulation, adjuvants, and alternate routes of administration. Recently, the nasal passageway has been recognized as a promising route, as mucosally delivered vaccines have the advantage of inducing protection at both mucosal surfaces, a common site of infection, and systemically. Human adenovirus serotype 5 (Ad5) is a candidate vaccine vector capable of being delivered through several routes and inducing strong immune responses to its delivered transgene. The studies presented include vaccination strategies following different routes of administration with various formulation components to determine the ability of Ad5 to deliver its transgene and induce immune responses. The first study screens formulation candidates’ effects on an Ad5-based vaccine’s transduction in vitro, cellular and humoral immune responses in vivo, and efficacy upon challenge in mice. Screening formulation candidates in vitro can eliminate ineffective formulations, thereby limiting animal testing. An Ad5-based Ebola virus vaccine delivered in a combination of mannitol, sucrose, and the surfactant, pluronic F68, improves survival against lethal Ebola challenge in a mouse model compared to delivery in PBS alone. The second study tests the effect of an intravenously delivered Ad5-based vaccine complexed with anti-Ad5 neutralizing antibodies on cellular and humoral immune responses. Different antibody ratios complexed to the Ad5 vector are able to induce disparate cellular and humoral responses. Ratios initiating a strong humoral response towards the Ad5 vector correlate with a reduction of the humoral response against the transgene and few transgene targeted effector T cells. Accordingly, ratios leading to minor humoral responses to the Ad5 vector resulted in stronger humoral responses to the transgene and a strong effector memory T cell response. Taken together, these studies provide insight on how to achieve necessary immune responses in vaccine protocols by testing routes of administration, formulations, and surface modifications of the Ad5 vector. / text

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

DNA vaccines offer unique promise as a means of generating immunity against infectious and malignant disease. Unfortunately a number of obstacles, including rapid degradation of naked plasmid DNA (pDNA), poor cellular uptake by antigen presenting cells (APCs) and subsequent low levels of gene expression have limited the ability of DNA vaccines to raise sufficient immune responses towards the target antigen. This thesis is focused on investigating the immunostimulatory potential of liposomal nanoparticulate (LN) formulations of pDNA (stabilized plasmid lipid particles; SPLP) and cytosine-guanine oligodeoxynucleotides (CpG-ODN; LN CpG-ODN), and examining their ability to act together as a non-viral DNA vaccine in attempt to address the shortcomings of current DNA vaccine approaches. One focus of this thesis concerns investigating the immunostimulatory activity of LN formulations of CpG-ODN and pDNA. It is shown that despite dramatic differences in pharmacokinetics and biodistribution of LN CpG-ODN following intravenous (i.v.) and subcutaneous (s.c.) administration the resultant immune response is very similar, which is concluded to be due to the intrinsic ability of APCs to sequester LN CpG- ODN. In addition, it is demonstrated that lipid encapsulation dramatically enhances the immunostimulatory potential of pDNA and it is observed that SPLP maintains immunostimulatory activity in Toll-like receptor 9 (TLR9) knock-out mice. Together theses findings highlight the need for DNA-based therapies to consider both TLR9-dependent and -independent immunostimulatory activities of pDNA when constructing non-viral vectors. Furthermore, a new role for SPLP as a non-viral gene delivery vehicle for the generation of a systemically administered genetic vaccine in the presence of LN CpG-ODN is introduced. The ability of vaccination with SPLP to act prophylactically, to protect mice from tumour challenge, and therapeutically, in a novel vaccination strategy where the antigen is expressed at the tumour site as a result of SPLP-mediated transfection, is explored, demonstrating that in the presence of LN CpG-ODN SPLP possesses potential as a non-viral delivery system for DNA-based cancer vaccines. In summary, this work represents a substantial advance in the understanding of the immunostimulatory potential of both SPLP and LN CpG-ODN and provides insight into their ability to work together as a non-viral DNA vaccine.

Background: Rotavirus is one of the most common diarrheal diseases in children less than 5 years of age. Rotavirus vaccines have greatly reduced this burden in the United States. An examination was conducted to determine possible disparities in RV vaccination rates compared to DTaP. Methods: Children were actively enrolled during two rotavirus seasons from January-June of 2010 and 2011 in the Emergency Departments (ED) and inpatient floors from all Children's Healthcare of Atlanta (CHOA) sites (Scottish Rite, Egleston, and Hughes Spalding) with acute gastroenteritis (AGE). Data and a stool sample were collected from enrolled children and samples were tested for presence of rotavirus using an enzyme immunoassay (EIA) kit (Rotaclone). Vaccination records were abstracted from the state immunization registry and primary healthcare providers to examine complete and incomplete vaccination status. This cohort of children with vaccination records were used for this analysis. Cases were identified as children receiving a complete RV dose series and controls were identified as children with incomplete RV doses. A logistic regression model was used to determine disparities seen amongst children with incomplete vaccination status. Results: Of the 660 patients that were approached for this study, 414 participants were included in this retrospective cohort analysis. 46.9% had incomplete rotavirus vaccination status and were more likely to be positive for rotavirus AGE (OR 1.76, 95% CI 1.46-2.13). Black infants had a higher rate of incomplete RV compared to whites (p-value 0.0006). When controlling for covariates, racial differences were no longer significant (OR 1.37 95% CI 0.77-2.57); however household size (p-value 0.0343), age at onset of illness (p-value 0.0061), and DTaP vaccination status (p-value < 0.0001) were all significant in determining vaccination status for children. Conclusions: Racial disparities and socioeconomic differences are not evident in determining rotavirus vaccination rates; however, household size, a possible social determinant, has an effect on RV status. In addition, timely vaccinations are important in preventing incomplete RV vaccination status, due to RV vaccine age restrictions.

BACKGROUND: Nova Scotia has the highest rate of cervical cancer, predominantly attributed to the Human Papillomavirus (HPV). In 2007, the HPV vaccine was approved and a successful school-based program was implemented. Little is known however, which strategies used by public health nurses (PHNs) helps improve vaccine uptake. METHODS: A retrospective, exploratory correlation study examined the relationship between school-based PHN strategies, and uptake of HPV vaccine. RESULTS: HPV vaccine initiation was significantly associated with PHNs providing reminder calls for: consent return (p = .017) and missed school clinic (p = .004); HPV education to teachers (p < .001), and a thank-you to teachers (p < .001). Completion of the HPV series was associated with consents being returned to the students' teacher (p = .003), and a PHN being assigned to a school (p = .025). CONCLUSIONS: These findings will help guide PHN’s best practice for optimal uptake of the HPV vaccine.

Clostridium difficile is a Gram-positive bacterium that is the most common cause of hospital-associated and antimicrobial-associated diarrhea in humans. Monteiro and co-workers have discovered that C. difficile expresses three cell-surface polysaccharides, named PS-I, PS-II and PS-III. Interestingly, PS-I was determined to be present in a ribotype 027 strain, the ribotype responsible for recent deadly outbreaks worldwide. In this work, the total chemical synthesis of the PS-I pentasaccharide with a linker molecule by a linear synthesis strategy from four monosaccharide building blocks is described: α-L-Rhap-(1→3)-β-D-Glcp-(1→4)-α-D-Glcp-(1→2)-α-D-Glcp-(1→O(CH2)5NH2 3 ↑ 1 α-L-Rhap The synthesized PS-I pentasaccharide will be conjugated to a protein carrier for evaluation as an anti-C. difficile glycoconjugate vaccine.

Constipation and diarrhea are common in autistic patients. Antibiotic treatment against bacteria appears to partially alleviate autistic-related symptoms. The bacterium Clostridium bolteae has been shown to be overabundant in the intestinal tract of autistic children suffering from gastric intestinal ailments, and as such is an organism that could potentially aggravate gastrointestinal symptoms. Investigation of the cell-wall polysaccharides of C. bolteae was employed in order to evaluate their structure and immunogenicity. Exploration revealed that C. bolteae produces a conserved specific capsular polysaccharide comprised of rhamnose and mannose units: [->3)-α-D-Manp-(1->4)-β-D-Rhap-(1->], which is immunogenic in rabbits. This is the first described immunogen of C. bolteae and indicates the prospect of using this polysaccharide as a vaccine to reduce or prevent colonization of the intestinal tract in autistic patients, and as a diagnostic marker for rapid detection. This diagnostic target can be used in a multivalent vaccine, which may potentially include Sutterella and Desulfovibrio.