Vaccination is one of the most efficacious public health interventions1 and has been increasingly used to combat non-infectious diseases. Mechanisms underlying vaccine responses overlap with those regulating immune responses in health and disease. Therefore, an understanding of mechanisms underpinning these responses will have broad implications. Variation in immune response genes contributes to impaired vaccine responses2-4. Understanding the contribution of genetic variants to vaccine responses is likely to be particularly important in early life given the generalized functional immaturity of the immune system in infants and the highly variable kinetics of its maturation over the first few years of life5-7. However, studies of genetic influences on early childhood vaccine responses are scarce. Since a number of genes from several pathways are likely to be important, a targeted approach is necessary. This thesis explored the effects and interactions of genes associated with atopy, as atopy, or the genetic risk for it, has been associated with modulation of early childhood vaccine responses. This thesis aimed to: 1) investigate genetic variants associated with atopy on early childhood vaccine responses; 2) examine interactions between these genetic variants and non-genetic factors; 3) approach developmental genetic influences on genetic effects and their interactions; and 4) extend findings on vaccine responses to other immunological phenotypes and disease outcomes.

The ground work for this research thesis was completed seven years ago when the Dow Pharmaceutical Company selected Muncie, Indiana to test their new rubella vaccine. In the Fall of 1970, 311 seronegative elementary school children were innoculated with HPV-77, DK12 rubella vaccine. Of the 302 children who seroconverted, 98 were available for follow-up six years post innoculation. The participant's sera drawn six years previously was recovered in order to determine a six week and six year post innoculation titer on paired specimens. All 98 children, when retested, has measurable antibody. The geometric mean titer six years post innoculation was 55; a 14% decrease from the geometric titer of 64 six weeks after innoculation. At the six year point in time, there was at least a 9.2% incidence of subclinical reinfection, detected by a fourfold rise in the HI-titer, within the study group.Ball State UniversityMuncie, IN 47306

Immunizations are an essential part of children’s healthcare; however, the associated distress can have short- and long-term negative ramifications for children. Parents’ procedural behavior is one of the strongest predictors of children’s distress. The current study evaluated whether an interactive computer training program influenced parents’ knowledge of the impact that their behavior has on their children or their actual procedural behavior during children’s immunizations. 90 parents and their 4- to 6-year-old children receiving immunizations participated. Overall, findings suggest that using a computerized training module to enhance parent knowledge and behavior is helpful but requires improvements in some areas to optimize training.

Syfte: Syftet med denna studie var att jämföra BVC-sjuksköterskors och föräldrars upplevelse av vaccinationstillfället samt skattning av barns smärta i form av skriktid vid två typer av vaccinationstekniker, dubbelvaccinering respektive en injektion i taget, när barnet ska ha två sprutor vid samma vaccinationstillfälle. Metod: Studien är en jämförande deskriptiv studie med kvantitativ ansats. Från både Stockholm och Uppsala valdes 50 barn ut konsekutivt varav 25 barn från Stockholms län samt 25 barn från Uppsala län. Datainsamling skedde med hjälp av enkäter samt mätning av skriktid. Dataanalysen genomfördes med hjälp av chitvåtest samt t-test. Resultat: Det fanns signifikanta skillnader vad gäller både BVC-sjuksköterskors och föräldrars upplevelser av vaccinationsproceduren. Skillnader kunde även ses såväl hos både föräldrar (p=0,020) och BVC-sjuksköterskor (p=0,032) när de fick skatta sin upplevelse av barnets smärta i samband med vaccinationen. Skriktiden visade inte någon signifikant skillnad (p=0,051) mellan de olika vaccinationsteknikerna. Slutsats: Resultatet av denna studie visade att barn som fick dubbelvaccinering upplevdes ha mindre ont när deras smärta skattades av både föräldrar och BVC-sjuksköterskor. Barn som fick sprutorna samtidigt skrek/grät generellt kortare tid än de barn som fick en spruta i taget, skillnaden visade dock ingen signifikans. Flertalat föräldrar i denna studie föredrog dubbelvaccinering. / Aim: The aim of this study was to compare child health center nurses' and parents' experience of the immunization and the child's estimated pain in terms of cry duration when two types of vaccination techniques were used, simultaneous versus sequential immunization injections, when the child are given two shots at the same occasion. Methods: The study is a comparative descriptive study with quantitative approach. From both Stockholm and Uppsala 50 children were selected consecutively with 25 children from the Stockholm and 25 children from the Uppsala. Data collection was done by means of questionnaires and measurement of cry duration. Data analysis was performed using the chi-square test and t-test. Results: There were significant differences from both nurses' and parents' perceptions of the vaccination procedure. Differences could also be seen in terms of the child's pain when both parents' (p=0,020) and nurses' (p=0,032) rated the child's pain associated with the immunization. Cry duration did not show a significant difference (p=0,051) between the two vaccination techniques. Conclusions: The results of this study showed that the children who received two vaccinations simultaneously were experienced by both parents’ and nurses’ to have less pain. Children that received the two injections at the same time cried less in general then the children that received the two injections one by one, the difference was not however significant. Most of the parents in this study preferred that the injections should be given at the same time.

In the past, when deciding the asset allocation, fund managers only concerned the factors of assets. This incomplete way may let pension funds not cover their liabilities. To solve this problem we integrate the factors which influence fund¡¦s assets and liabilities and focus on surplus, which means assets minus liabilities. We use Surplus Optimization Model and Immunization Theory to construct our Liability Driven Investment and Dual Duration Matching Model. We decompose duration to real interest rate duration and inflation rate duration to control the sources of interest rate. Through this method, we can enhance the efficiency of asset allocation to ensure paying pension annuity punctually and avoid the risk of interest rate. Our sample period is Sept. 2001 to Aug. 2005 and sampling frequency is monthly. We use the common investment tools, stocks index, government bond index, 5 years corporate bonds, 3 years bank deposit, 30 days commercial papers, to be the assets we can allocate. We discover that when using liability driven investment and duration matching the longer years we consider the longer assets duration we need. Because government bond index¡¦s duration is shorter than stocks index¡¦s. When we consider longer years the weight of government bond index will decrease and the weight of stocks index will increase. When considered years are 50, the weight of government bond index is 54.74% and the weight of stocks index is 45.26%. The ratio of equity assets to fixed income assets is 84.51% that is similar with pension fund¡¦s ratio, 86.13%. No matter how many years we consider, the weight of bonds is high. But in pension funds¡¦ target allocation the weight of bonds is only 16% and the weights of bank deposit and T-bills are 31%. To take immunization strategy and improve the long term revenue, a large proportion should be allocated from bank deposit and T-bills to bonds.

Master's thesis. / Format: PDF. Bibl.

This dissertation research explores how values regarding sexuality, morality, responsibility, protection, trust, and risk — expressed through parent, daughter, and healthcare provider relationships and interactions — inform parental decisions regarding the Gardasil® vaccine. In particular, the research examines the competing and conflicting meanings that parents and providers ascribe to vaccination and how actors position the vaccine within a wider set of negotiated, value–laden discourses. Because these narratives are situated within a larger structural field that shapes the landscape in which providers and parents interact, relevant historical and structural factors, including vaccine policy, cost, and compensation are discussed.

The development of hybridoma technology nearly forty years ago set the foundation for the use of antibodies in the life sciences. Subsequent advances in recombinant DNA technology have allowed us to adapt antibody genes to various screening systems, greatly increasing the throughput and specialized applications for which these complex biomolecules can be adapted. While selection systems are a powerful tool for discovery and evolution, they can be slow and prone to unintended biases. We see computational approaches as an efficient process for rapid discovery and engineering of antibodies. This is particularly relevant for biodefense and emerging infectious disease applications, for which time is a valuable commodity. In the first chapter of this work, we examine computational protocols for ‘supercharging’ proteins. This process resurfaces the target protein, adding charged moieties to impart specialized functions such as thermoresistance and cell penetration. Current algorithms for resurfacing proteins are static, treating each mutation as an event within a vacuum. The net result is that while several variants can be created, each must be tested experimentally to ensure the resultant protein is functional. In many cases, the designed proteins were severely impaired or incapable of folding. We hypothesize that a more dynamic approach, keeping an eye on energetics and the consequences of mutations will yield a more efficient and robust method for supercharging, successfully adding charges to proteins while minimizing deleterious effects. We continue on this theme applying the successful algorithm to supercharging antibodies for increased function. Utilizing the MS2 model biosensor system, we rationally engineer charges onto the surface of an antibody fragment, increasing thermoresistance, minimizing destabilizing effects, and in some cases actually increasing affinity. Finally, we apply next-generation sequencing approaches to the rapid discovery of antibodies directed against the Zaire Ebolavirus species. We utilize a local immunization strategy to generate a polarized antibody repertoire that is then sequenced to provide a database of antigen-specific variants. This repertoire is probed in silico and individual antibodies selected for analysis, bypassing time- and resource-consuming selection experiments. / text

U.S. immunization and well child-care rates are below desired levels with lower income individuals being at higher risk for receiving inadequate care. To enhance the understanding of motivating factors to health care utilization, this study explored relationships between a mother's interaction style (secure, anxious, avoidant), her reported experiences with pediatric health care and her child's utilization of pediatric health care. Participants included 126 US-born, English-speaking women with an infant 12 to18 months of age. Linear regression analyses found no bivariate associations between maternal interaction style and reported experiences of care. Poisson regression analyses measured associations of maternal interaction style, reported experiences of care, and moderating variables with health care visits and immunizations received. Main effect models found no associations between maternal interaction style and reported experiences of care. Significant associations were identified between provider ratings and sick visits. There were no associations between provider office ratings and utilization rates. When interaction style and provider/provider office ratings were included in the model, high provider ratings (P<.05) and high anxious interaction scores (p<.0001) were associated with more sick visits while higher avoidant interaction style scores (p<.01) were associated with decreased use of sick visits. Multivariate modeling identified provider rating (p<.05) and anxious interaction score (p<.01) as main effects, child's health rating as a confounder, as well as target child being mother's first, WIC/Healthy Start participation, maternal bonding and feelings about going to the doctor acting as moderators to associations between interaction style and sick/follow-up visits. Secure interaction style scores were associated with increased use of emergency department visits, controlling for the confounding effects of maternal bonding and the moderating effects of child's health status and maternal age. Findings indicate that, in some cases, maternal interaction style is associated with how and when mothers access health care for their children. The confounders and moderators identified also highlight the need for more understanding regarding what motivates individuals. Finally, there were racial and ethnic differences including higher rates of avoidant interaction styles in Black, non-Hispanic mothers. Predicting health care utilization patterns will help better target the specific needs of mothers and ultimately improve health outcomes.

Immunotherapy for Alzheimer\'s disease has emerged as a promising approach for clearing pathological tau protein conformers. To explore this kind of treatment we tested an active immunization with pseudo-phosphorylated tau fragments in P301L tangle model mice that develop neuronal tau aggregates as observed in frontotemporal dementia and Alzheimer’s disease. We found that an immunization reduces neurodegeneration in α-motor neurons in the spinal cord and slows progression of the tangle-related behavioral phenotype. Performance on behavioral assays correlated with tau pathology at the corresponding spinal cord level. Interestingly, a slowed progression of these tauopathy related characteristics were only seen in mice that received a specific immunization with pseudo-phosphorylated tau fragments, not in animals that received a non-specific activation of the immune system. An immunization witch pseudo-phosphorylated tau fragments may be a valuable therapeutic option in targeting one of the major hallmarks of Alzheimer’s disease and frontotemporal dementia.