Browsing by Subject "Vaccination"
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Item Early Events Following Oral Transmission of Simian Immunodeficiency Virus: From Viral Entry to Host Immune Response(2005-08-11) Milush, Jeffrey Martin; Sodora, Donald L.Approximately 40 million people worldwide are infected with HIV, the causative agent of AIDS. The primary mode of HIV transmission (75% of all transmissions) between individuals occurs across mucosal tissues (vaginal, rectal, oral). The goal of this thesis was to assess the virologic and immunologic events following oral inoculation of macaques with Simian Immunodeficiency Virus (SIV) and correlate these findings with disease progression. To assess the virologic events involving viral entry and spread, macaques were orally inoculated with SIV and necropsied at early times post-infection (days 1 - 14). These studies were the first to identify the preferential entry sites for the virus as the oral and esophageal mucosa, as well as the tonsils. Furthermore, SIV rapidly disseminated to peripheral lymph nodes resulting in systemic infection by 2 to 4 days post-infection. The rapidity with which SIV spreads throughout the lymphatics indicates a major obstacle for a vaccine recall immune response to eliminate infected cells prior to dissemination. Analyses of immunologic events through the assessment of mucosal innate immune gene expression, as well as the initiation of the adaptive immune response, were undertaken in a second group of SIV orally inoculated macaques. Two hypotheses were proposed: 1) An innate mucosal immune response at the site of entry (oral mucosa) would result in the induction of a timely SIV-specific adaptive immune response; and 2) Maintaining a healthy mucosal barrier during chronic infection would prevent the onset of opportunistic infections. My data support hypothesis one, as during early times post-infection (2 - 21 days), gingival mucosal innate response gene expression correlated with the ability toinduce timely SIV antibodies and reduce plasma viral loads. In addition, my data assessing events during chronic infection (day 70) indicated an association between elevated expression of mucosal innate response genes, particularly chemokines, with an absence of opportunistic infections, thus supporting hypothesis two. From these studies assessing viral and immune correlates of SIV transmission, I conclude that vaccines capable of inducing high titer neutralizing antibodies at the mucosa, as well as increased mucosal innate immune responses, will be most efficacious in preventing mucosal HIV transmissions.Item Effects of cytosine-phosphate-guanosine oligodinucleotides (CpG-ODNs) on oral immunization with protein antigen or replicating parasite(Texas A&M University, 2005-08-29) Ameiss, Keith AllenThe purpose of this research was to investigate selected methods of mucosal immunization for commercial chickens. Induction of mucosal immunity in commercial chickens through the use of orally administered subunit vaccines or through immunomodulation of the host??s response to live vaccines may be a viable means to control enteric infections in commercial poultry. In the present investigations we evaluated a means for delivering protein antigen in the drinking water and the use of CpG-ODNs, a recently reported mucosal adjuvant, in order to both improve this response and to modulate the host??s immune response when vaccinated with field strains of Eimeria acervulina and Eimeria tenella. In order to evaluate the efficacy of immunizing commercial poultry with subunit vaccines through the drinking water we chose the model antigen Bovine Serum Albumin (BSA). Chicks were administered BSA via intraperitoneal (I.P.) injection, oral crop gavage, or orally through the addition of BSA to the drinking water. These experiments demonstrated the efficacy of drinking water administration to induce antibodyproduction in the serum, intestine, and bile. When BSA was co-administered with CpGODNs we observed a modest increase in this response dependent upon dose. To evaluate the immunomodulation of the host response to live parasite using CpG-ODNs we used three administration models. The first was a single dose of CpGODNs with a trickle immunization regime of Eimeria acervulina. The second was coadministration of CpG-ODNs with a clinical dose of Eimeria acervulina or tenella. The third was pre-administration of CpG-ODNs 24 hours prior to the clinical dose of either species. These studies demonstrate that the first and third models were effective in reducing lesions and improving performance.Item Effects of Probiotic Administration During Coccidiosis Vaccination on Performance and Lesion Development in Broilers(2010-10-12) Klein, AnthonyThe principal objective of this investigation was to evaluate coccidiosis vaccination, with or without probiotic administration, for effects on broiler performance and clinical indices of infection due to field strain Eimeria challenge during pen trials of commercially applicable durations. During trials 1 and 2, body weights of vaccinated broilers were reduced (P<0.05) compared to other experimental groups during rearing through the grower phase. Final body weights, however, were not different among experimental groups at the termination of each trial. Similarly, feed conversion in trials 1 and 2 was increased (P<0.05) in vaccinated broilers during rearing through the grower phase when compared to non-vaccinated broilers. Significant improvements (P<0.05) in feed conversion were measured in trials 1 and 2 in vaccinated broilers during the withdrawal phase of grow-out. Probiotic administration significantly reduced (P<0.05) feed conversion during the withdrawal phase of trial 2. During trial 3, body weights of broilers in the vaccine with probiotic (water) group were higher (P<0.05) at termination (d 44) than all other experimental groups and equivalent to the ionophore alone and ionophore with probiotic groups. Similarly, cumulative mortality corrected feed conversion ratio (FCR) was lower (P<0.05) in broilers from the vaccine with probiotic (water) group compared to negative controls, and not different from FCR in ionophore administered broilers. Trial 2 observations revealed body weight gains among vaccinated broilers that were significantly increased (P<0.05) during a seven day clinical field strain Eimeria challenge period compared to non-vaccinated broilers. Both probiotic and vaccine significantly decreased (P<0.05) gross lesion scores in upper and mid-intestinal regions. A significant reduction (P<0.05) in gross lower intestinal lesion score was also observed in the vaccine alone group. In Trial 3 general observations showed, broilers in the ionophore alone group were associated with higher (P<0.05) microscopic mid and lower intestine lesion scores when compared to broilers receiving vaccine or vaccine + probiotic. These data suggest that co-administration of probiotic during coccidiosis vaccination results in performance parameters that are improved when compared to vaccination alone and indistinguishable from protection conferred by feeding an ionophore in the presence of field strain Eimeria.Item Essays in health economics(2012-05) Mulligan, Karen Michelle; Abrevaya, Jason; Black, Sandra; Hamermesh, Daniel; Trejo, Stephen; Hayward, MarkThis dissertation consists of three chapters on health economics, two of which focus on contraception and the third on vaccination. Chapter one examines the impact of state-level contraception insurance coverage mandates on women's fertility outcomes. It utilizes variation in mandated insurance coverage for contraception across states and over time to determine the causal impact of insurance coverage of contraception on fertility outcomes, specifically abortion rates and birth rates. State-level results indicate that a mandate decreases abortion rates by 6% in the year of introduction and decreases birth rates by 3% two years following introduction, with the magnitude of both effects remaining steady over the long run. Chapter two utilizes longitudinal data on varicella (chicken pox) immunizations in order to estimate the causal effects of state-level school-entry and daycare-entry immunization mandates within the United States. We find significant causal effects of mandates upon vaccination rates among preschool children aged 19-35 months; these effects appear in the year of mandate adoption, peak two years after adoption, and show a minimal difference from the aggregate trend about six years after adoption. For a mandate enacted in 2000, the model and estimates imply that roughly 20% of the short-run increase in state-level immunization rates was caused by the mandate introduction. We find no evidence of differential effects for different socioeconomic groups. Combined with the previous cost-benefit analyses of the varicella vaccine, the estimates suggest that state-level mandates have been effective from an economic standpoint. Chapter three utilizes variations in access to emergency contraception (EC) across states to determine the impact of over the counter access on abortion rates, birth rates, and risky sexual behavior. Using state-level data, a flexible time specification finds that giving individuals over the counter access to EC reduces births and increases risky behavior, which is captured by STD rates. These effects are larger for adults compared with teenagers, however, there are not significant differential effects by race. Finally, the effects are increasing over time following the legislation.Item Influence of Diet on Performance Parameters, Intestinal Lesion Development, and Oocyst Cycling in Live Oocyst Vaccinated Replacement Broiler Breeders(2010-10-12) Oden, Leslee AnnTwo consecutive experiments were conducted to evaluate the influence of dietary composition, specifically protein and amino acid profile, on performance parameters, oocyst output, and lesion development in male and female replacement broiler breeders of two different genetic lines vaccinated with a live coccidiosis vaccine. Dietary formulations were based on either breeder specific recommendations or formulations of a broiler integrator. On day 28, males of each genetic line were added to female pens to evaluate the effect of co-mingling on male performance. Lesion assessment was performed on three separate occasions per each experiment. Fecal material was collected to determine oocyst cycling patterns. During experiment 1, flock uniformity was improved (P less than/equal to 0.05) in Line A males fed the integrator diet. Increased body weight and improved uniformity of Line B females was observed with the breeder recommended diet. Co-mingling negatively impacted (P less than/equal to 0.05) male body weight. Multiple oocyst peaks were observed in both genetic lines, with the first peak occurring at approximately 16 to 18 days post placement. This first peak tended to have the highest observed magnitude and corresponded with the highest level of intestinal lesions observed during the experiment. In experiment 2, diet impacted (P less than/equal to 0.05) average body weight in Line A males, Line B males, and Line B females. Line A males fed the breeder recommended diet had increased (P less than/equal to 0.05) body weight at the termination of the experiment. Line B males and females fed the breeder recommended diet had increased (P less than/equal to 0.05) body weights throughout the experiment beginning on day 7. Negative effects (P less than/equal to 0.05) on male body weight resulting from co-mingling were observed. Oocyst peaks were delayed and at a lower magnitude in both genetic lines compared to peaks observed in experiment 1. Dietary interactions were observed in both experiments where magnitude of peak, duration of oocyst output, and severity of lesion development was influenced by diet in both male and female genetic lines. These data indicate that co-mingling negatively impacts male performance and dietary composition can impact male and female performance, oocyst cycling, and lesion development during coccidiosis vaccination in replacement broiler breeders and should be taken into consideration when rearing replacement broiler breeders.Item Influence of dietary composition on coccidiosis vaccination efficacy in broilers(Texas A&M University, 2007-04-25) Lee, Jason ThomasThis research program included a series of experiments to investigate the effect of starter diet protein level on the performance of broilers vaccinated with Coccivac????-B and subsequently challenged with a mixed species Eimeria challenge compared to nonvaccinated broilers. Pre-challenge performance data indicates that vaccination may decrease body weights and increase feed conversion ratio (FCR) with vaccination. The time period associated with the observed effects is between 13 to 17 d of age. This reduction in performance of vaccinated broilers versus non-vaccinated broilers was eliminated by the conclusion of the experiments (27 d) in the higher protein diets. Vaccination was effective at generating protective immunity against the Eimeria challenge evidenced by significantly increased body weight gains, improved feed conversions, reduced post-challenge mortality, and reduced lesion development in vaccinated broilers compared to non-vaccinated. The final experiment included the comparison of Coccivac????-B to Bio-Cox???? (salinomycin) for controlling field strain Eimeria in broilers reared on two different dietary rations varying in protein concentration. Diet A had a lower protein concentration than Diet B. On day 14, Eimeria collected from commercial broiler farms in Texas were spray applied to the litter in all pens. Broilers reared on Diet B were heavier at Day 40 while body weights at day 50 were similar for all groups. Broilers fed Diet B had lower FCR during the starter and finisher diets. Broilers fed salinomycin had lower FCR for the starter and grower diets while vaccinated broilers had lower FCR during the withdrawal period. Cumulative FCR for the entire grow out period were similar for all groups. These data indicate that vaccination can be utilized as an anticoccidial preventive and are suggestive that reduced protein concentration of starter diets can lead to significant losses in broiler performance when utilizing a vaccination program to prevent coccidiosis. Feeding an appropriately formulated diet while vaccinating broilers with Coccivac????-B as an alternative to the use of salinomycin yields at least equivalent if not elevated performance in the presence of field-strain Eimeria during grow-out with no effect on the cost of production.Item Intradermal Administration of RiVax, a Ricin Vaccine(2010-11-02T18:18:52Z) Selvaduray, Praveena; Vitetta, EllenRicin toxin is a CDC Level B Biothreat due to its extreme toxicity and ease of production. The most effective method for minimizing ricin toxicity in humans is prophylactic vaccination. We have previously described the efficacy and safety of RiVax, a recombinant mutant of ricin A chain (RTA). RiVax has no residual toxicity from either its ribotoxic site or its vascular leak-inducing site. When administered by intramuscular (IM) injection, it was safe and immunogenic in mice, rabbits, and humans. A three dose regimen of IM administered RiVax also protected mice from an LD50dose of ricin delivered by injection, gastric gavage or aerosol. In this study we have attempted to increase the utility and immunogenicity of RiVax. To this end, we have compared intradermal (ID) vs. IM administration of RiVax by evaluating the following parameters of vaccine efficacy: (1) short-term antibody responses and protection of mice from a 10X LD50of ricin following a three dose vaccine regimen; (2) long-term antibody responses and protection of mice from a 10X LD50of ricin following a three dose vaccine regimen; (3) protective effect of a single high dose of RiVax from a 10X LD50dose of ricin; (4) the minimum dose of ricin at which fully vaccinated animals are no longer protected; (5) the rate of antigen trafficking to draining lymph nodes (DLN) following administration of RiVax. In the short term, when RiVax was delivered with alum, very low doses of vaccine administered ID were superior to the same low doses administered IM, with regard to both antibody production and protection against ricin delivered by injection, gavage, or aerosol. Low doses of ID vaccine were also superior in maintaining lung function in mice exposed to aerosolized ricin. Comparing the same parameters in the long term or after a single dose of RiVax, ID and IM vaccinations were equally effective. Both ID and IM vaccination were also similar in their ability to protect mice from a supra-lethal challenge with injected ricin. One possible explanation for the improved efficacy of low doses of RiVax administered ID was that the vaccine trafficked more effectively to the DLNs. This appeared to be the trend, albeit not a statistically significant one. Given the increased efficacy of low doses of ID vaccine in protecting mice against ricin delivered to the lung and gut, we suggest that it should be considered for testing in humans.Item Optimal vaccination strategies for varicella and herpes zoster(Texas Tech University, 1996-12) Thrasher, David BruceIn March of 1995, the United States Food and Drug Administration approved a vaccine for the varicella-zoster virus (VZV) infection [7]. This vaccine was developed in the 1970's in Osaka, Japan and has been used extensively in the Asian and European continents. Prior to March 1995, the United States had restricted the use of the VZV vaccine to immunocompromized patients(chemotherapy and AIDS patients). The varicella-zoster virus causes varicella, or chickenpox, in the majority of the population at a young age. Estimates range from 3.5 to 4 million cases of chickenpox per year in the United States [3, 7]. For most children who contract varicella, few complications arise. Yet for infants,steroid or immunocompromized patients or women who are pregnant, the varicella infection may cause complications ranging from severe rashes, congenital varicella syndrome to death [3, 16, 26]. After an individual has been infected and survives varicella infection, the virus travels to the dorsal root ganglia at the base of the spinal cord and becomes dormant [7, 16]. The virus remains latent in this location usually for decades [7, 16]. If the virus reactivates, it causes an acute infection, herpes-zoster, similar to the original varicella infection except for the intensity. Herpes-zoster or shingles, usually affecting only a single dermatome [16], increases in incidence with age [14, 20, 25, 27, 34]. There have been 300,000 to 850,000 cases of zoster per year reported in the United States in recent years [14, 30, 33]. A syndrome known as postherpetic neuralgia, (PHN), pervasive pain, which can last from one month up to one year is considered the worst comphcation associated with zoster [14]. There is also an age-related incidence of PHN with zoster patients: at 60 years old, an individual with zoster has a 50% chance of developing PHN, but at 90 years, PHN occurs in 90% of zoster patients [31]. Although treatments for PHN have increased in effectiveness over the years, this still represents a sizable risk for the elderly.Item Overlooked casualties : stories of families affected by vaccine-preventable diseases(2012-05) Haelle, Tara Susan; Darling, Dennis Carlyle; Minutaglio, BillThe invention of the vaccine has been one of the greatest public health triumphs of the modern world. Each new vaccine has saved thousands - even millions - of lives worldwide, but this success has been fraught with controversy over the safety and even the effectiveness of vaccines. Vaccines have not always had a spotless safety record, but today’s vaccines are incredibly safe and continue to protect millions of people against diseases that have significantly declined or nearly disappeared from the developing world. It is this very success that has led many people to forget, or never discover, what those diseases are and how destructive they can be. This report tells the story of several families whose lives were deeply affected by vaccine-preventable diseases, accompanied with images that help tell their story. Following these stories is a broader discussion of the issues related to vaccines, the misunderstandings and misinformation that often circulate about them, a brief mention of their safety and efficacy, and a general discussion of many of the diseases they can prevent.Item The potently neutralizing monoclonal antibody 1B7 : its unique epitope, effects on intracellular trafficking, and elicitation upon infection with pertussis(2010-08) Sutherland, Jamie Nicole; Maynard, Jennifer Anne, 1974-; Georgiou, George; Alper, Hal; Brown, Katherine; Truskett, Thomas M.Disease caused by Bordetella pertussis persists with rates increasing over the past decade in industrialized countries. A hindrance to vaccine development has been the lack of a clear serological correlate of protective immunity. Pertussis toxin (PTx), an AB-type toxin, is one of the bacteria’s major virulence factors and among the lead candidates for potential correlates. Of the numerous monoclonal antibodies (mAbs) binding PTx, the murine IgG2a mAb 1B7 is potently neutralizing in all in vitro assays and in vivo murine models of infection. 1B7 binds an epitope on the enzymatic S1-subunit of PTx with some linear elements but previous work was unable to more precisely define the epitope or determine its exact mechanism of protection. We characterize the epitope bound by 1B7 on PTx-S1 in molecular detail and define energetically important interactions between residues at the interface including six residues on PTx-S1 and six residues on 1B7. Using this information, a model of the 1B7-S1 interaction was developed, indicating a predominantly conformational epitope located on the base of S1 near S4. The location of this epitope is consistent with previous data and is shown to be conserved across several naturally occurring strain variants including PTx-S1A, B, D, and E in addition to the catalytically inactive 9K/129G variant. Using immunofluorescent microscopy, it was determined that 1B7’s unique mode of action lies in its ability to bind to the toxin and co-traffic into target cells. Upon endocytosis, 1B7 protects from PTx intoxication by redirecting its intracellular retrograde trafficking. In order to determine whether antibody responses are differently induced by infection or acellular vaccination, we analyzed sera from 30 adults with confirmed exposure to pertussis and 30 recent vaccinees. Natural infection resulted in significantly higher titers of anti-PTx-S1, 1B7-like, and 11E6-like antibodies, while overall anti-PTx titers were similar to vaccinated samples. We also observed a direct correlation between in vitro protection and the presence of 1B7-like and 11E6-like antibodies. Thus, natural infection elicits higher titers of protective antibodies indicating that the use of detoxified PTx in current acellular vaccines although highly immunogenic results in the elicitation of predominantly non-neutralizing antibodies.Item Validation of dog treats and bones for the presence of Salmonella through in-plant analysis and inoculation challenge studies(2012-05) Daniels, Paden; Miller, Markus F.; Brashears, Mindy M.; Brooks, Chance J.Salmonella is a continual problem within the pet food industry. Salmonella in pet food and treats can lead to a potential human Salmonella infection through the handling of these products. The objective of this experiment was to determine the prevalence of Salmonella in various dog treats through an in-plant analysis study and an inoculation challenge study. For the in -plant analysis study, thirty raw and thirty cooked samples of lamb lung cubes, weasands (weasands), pizzles (steer pizzles), and jumbo pizzles were delivered to the Texas Tech University Food Microbiology Laboratory on ice and analyzed by the FDA approved BAX system method for detection of Salmonella. When testing raw products, 7 of 30 weasands, 0 of 30 lamb lung cubes, 26 of 30 pizzles, and 29 of 30 jumbo pizzles were positive for Salmonella. For the cooked products, 1 of 30 taffy’s was positive for Salmonella¸ while the other products had no positive cooked samples. During the inoculation challenge, two different lots of raw samples of liver tripe steaks, lamb lung cubes, taffy’s, and pizzles were delivered on ice to Texas Tech University’s Experimental Sciences Building. Fifteen samples from each lot of products were inoculated with a four-strain Salmonella cocktail at 102-5 CFU/g. After a 30-min attachment period, five control samples were sampled for initial concentration. Remaining samples were cooked in accordance with the standard cooking procedure established by the company. Before and after cooking, samples were serially diluted and plated onto xylose lysine deoxycholate agar (XLD) with a tryptic soy agar overlay for injured cells. If no colonies were present on XLD plates, detection was performed by the BAX system and immunomagnetic separation (IMS) with Remel Salmonella agglutination kit for confirmation. Statistical analysis was performed using SAS program with a significance level of α = 0.05. Cooking reduced (P < 0.01) Salmonella of lamb lung cubes by 2.85 log with one positive sample after cooking (<10 CFU/g present). In addition, cooking reduced (P < 0.01) Salmonella of liver tripe steaks by 3.11 log, taffy’s by 2.85 log, and pizzles by 5.47 log, leaving no positive samples after cooking. A baseline study was performed for pizzles and compared between two groups (ice vs. normal). No difference between the groups (P > 0.05) at 2.59 logs for normal with no BAX positives and 2.46 logs for iced with 2 BAX positives. The processing procedures were validated by inoculation challenge study with an initial inoculum of 6.95 logs resulting in a complete reduction after cooking (P < 0.01). A similar inoculation challenge was performed on bones used for dog treats including femurs, white knuckle bones, large shank bones, and twin hooves. Cooking reduced (P < 0.01) Salmonella of femurs by 3.86 log, large shank bones by 5.77 log, and twin hooves by 4.53 log, and no positive samples were detected after cooking. Furthermore, cooking reduced (P < 0.01) Salmonella of white knuckle bones by 3.62 log, but one positive sample was detected after cooking. Based on these results, modification to the processing and cooking procedures for taffy’s and white knuckle bones was recommended to ensure safeness during times of high contamination. The results from the inoculation challenge suggest that the processing and cooking procedures would be effective if a high level of Salmonella contamination occurred.