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 Intradermal Administration of RiVax, a Ricin Vaccine(2010-11-02) Selvaduray, Praveena; Vitetta, Ellen S.Ricin 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 [News](1977-06-10) Williams, AnnItem [Southwestern News](1999-03-18) Manley, Jennifer HaighItem [Southwestern News](2001-04-23) Echeverria, Ione; Cofer, BrianItem [UT Southwestern Medical Center News](2006-01-30) Siegfried, AmandaItem Vaccine hesitancy(2021-05-21) DuVal, Tara