Generation of a linear epitope based multi-protein chimeric construct for prevention of Lyme disease in humans

Lyme disease (LD) is the most prevalent vector borne disease is North America with 300,000-600,000 human cases each year. Preventative strategies for LD in humans are poorly developed and largely inadequate. While preventive vaccines for LD are widely used in veterinary medicine, there are no vaccines available for use in humans. The goal of this study was to develop a human vaccine that can elicit antibody responses that kill spirochetes in both the tick and mammalian environments. The approach applied in this study centered on the development of chimeric epitope proteins, referred to as chimeritopes. Chimeritopes consist of a series of epitopes derived from one or more proteins or protein variants. Three chimeritope proteins designated as Chv1, Chv2 and Chv3 were designed. These proteins harbor the same set of 18 linear epitopes derived from 9 different OspC type proteins. They differ in epitope arrangement or by the presence or absence of linkers between specific protein segments. The immunogenicity of each protein was assessed in multiple animal models including mice, rats, and purpose bred beagles. Immunoblot, ELISA, and IFA analyses using sera from immunized animals demonstrated that the Chv proteins elicit IgG responses that recognize a diverse array of OspC type proteins. Anti-Chv and anti-OspA antisera displayed complement dependent bactericidal activity. To assess protective efficacy, purpose bred beagles were immunized with each vaccine formulation and then challenged by infestation with infected ticks. Efficacy was assessed by monitoring seroconversion, cultivation of tissue biopsies, clinical presentation and histopathological analysis of joints and tissues. All dogs vaccinated with the Chv2-OspA combination were fully protected. All dogs in this group were seronegative for LD, biopsy culture negative and did not develop LD associated symptoms including lameness or lesions in tissues or joints. In light of market concerns centered on the use of full length OspA in a human vaccine, epitope mapping was performed to identify a linear epitope that could be employed in development of a possible OspC-OspA chimeritope. A linear epitope, designated as OspA221-240was identified. Antisera to KLH-OspA221-240displayed potent and broad bactericidal activity. Interestingly, the OspA221-240epitope has homology to residues 244 to 263 of OspB suggesting that OspB may also be a potential candidate for inclusion in a human vaccine. This study establishes proof of principle for the use of OspC chimeritopes in LD subunit vaccines and highlights the need to employ a multi-valent, multi-antigen vaccine approach in development of a human LD vaccine

Social Stratification and Health in Dynastic Egypt: The Differential Effect of Disease Among the Elite and Working Classes

Social stratification in Dynastic Egypt between the elite and working class is suspected to have created differential health conditions for these two social classes. It is hypothesized that due to differing living conditions, resulting in varying levels of exposure to infectious pathogens, workloads, and quality of diet, the elite and working class will have dissimilar health conditions. Specifically, it is expected that the working class of Dynastic Egypt suffered ill health more often, and more severely, than the elite. The health conditions of the elite and working class were measured by the prevalence of the density-dependent disease tuberculosis, the workload-related disease osteoarthritis, and the diet-related dental caries. Analysis of these three diseases revealed that the elite and working class suffered from tuberculosis equally, due to similar living conditions. The working class was shown to have suffered more from osteoarthritis, due to lifetimes of heavy labor. However, the elite were shown to have suffered more from dental caries resulting from their diet rich in refined foods and sweets

Is It Choice or Is It Interest?: The Effect of Choice and Interest on the Cognitive and Affective Engagement of Elementary Students Performing a Reading Task

The author replicated and extended a study by Flowerday, Schraw, & Stevens (2004) that examined the effects of choice, topic interest, and situational interest on reading engagement, attitude, and learning in college-age students. The study was replicated using fourth and fifth graders as subjects. The study was extended to examine the effects of gender and reading ability cohort on the outcome measures. Participants randomly assigned to the choice condition made a blind choice of Packet A or B containing a non-fiction essay to read; participants assigned to the no choice condition were given one of the packets without being offered a choice. Outcomes were measured using scores on a multiple-choice test, a content essay, a personal reaction essay, and an attitude checklist. Results confirmed the 2004 finding that situational interest has the strongest effect on students\u27 attitude toward a reading task. Both topic interest and choice had a smaller but significant effect on attitude after situational interest was controlled for, indicating that topic interest and choice have a stronger influence on the attitude of elementary students than they do on college students. Participants in the choice group had higher situational interest levels and a more positive attitude toward the task. There was no difference in the performance outcomes of the choice and no choice groups. Neither gender nor reading ability cohort had an effect on interest level or attitude

The Effects of Development on Indian Water Rights: Obstacles and Disincentives to Development of Indian Water Rights

17 pages. Contains references

Word Families and Decoding by Analogy for Word Recognition

The purpose of this study was to determine if utilizing decoding by analogy through phonograms will increase second grade students’ word identification skills. Six second-grade students participate in the seven-week quantitative study. The six students received explicit instruction in phonogram study through decoding by analogy as a method of word attack to read an unknown word. In addition to the explicit instruction, the students had application time during the instruction to write and read the words in the context of literature. A pre-test post-test design helped determine student achievement in recognizing words in isolation with common phonogram patterns. The results indicated that all students increase their word recognition skills. This study raises questions about the best ways to instruct students for rapid recognition of words in isolation or in the context of literature