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Immunoprophylaxis and Therapy Commons

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Time-To-Infection By Plasmodium Falciparum Is Largely Determined By Random Factors, Mykola Pinkevych, Kiprotich Chelimo, John Vulule, James W. Kazura, Ann M. Moormann, Miles P. Davenport 2015 University of New South Wales

Time-To-Infection By Plasmodium Falciparum Is Largely Determined By Random Factors, Mykola Pinkevych, Kiprotich Chelimo, John Vulule, James W. Kazura, Ann M. Moormann, Miles P. Davenport

University of Massachusetts Medical School Faculty Publications

BACKGROUND: The identification of protective immune responses to P. falciparum infection is an important goal for the development of a vaccine for malaria. This requires the identification of susceptible and resistant individuals, so that their immune responses may be studied. Time-to-infection studies are one method for identifying putative susceptible individuals (infected early) versus resistant individuals (infected late). However, the timing of infection is dependent on random factors, such as whether the subject was bitten by an infected mosquito, as well as individual factors, such as their level of immunity. It is important to understand how much of the observed variation ...


A Human Type 5 Adenovirus-Based Trypanosoma Cruzi Therapeutic Vaccine Re-Programs Immune Response And Reverses Chronic Cardiomyopathy, Isabela Resende Pereira, Glaucia Vilar-Pereira, Virginia Marques, Andrea Alice da Silva, Braulia Caetano, Otacilio Cruz Moreira, Alexandre Vieira Machado, Oscar Bruna-Romero, Mauricio Martins Rodrigues, Ricardo T. Gazzinelli, Joseli Lannes-Vieira 2015 Instituto Oswaldo Cruz/Fiocruz

A Human Type 5 Adenovirus-Based Trypanosoma Cruzi Therapeutic Vaccine Re-Programs Immune Response And Reverses Chronic Cardiomyopathy, Isabela Resende Pereira, Glaucia Vilar-Pereira, Virginia Marques, Andrea Alice Da Silva, Braulia Caetano, Otacilio Cruz Moreira, Alexandre Vieira Machado, Oscar Bruna-Romero, Mauricio Martins Rodrigues, Ricardo T. Gazzinelli, Joseli Lannes-Vieira

Open Access Articles

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a prototypical neglected tropical disease. Specific immunity promotes acute phase survival. Nevertheless, one-third of CD patients develop chronic chagasic cardiomyopathy (CCC) associated with parasite persistence and immunological unbalance. Currently, the therapeutic management of patients only mitigates CCC symptoms. Therefore, a vaccine arises as an alternative to stimulate protective immunity and thereby prevent, delay progression and even reverse CCC. We examined this hypothesis by vaccinating mice with replication-defective human Type 5 recombinant adenoviruses (rAd) carrying sequences of amastigote surface protein-2 (rAdASP2) and trans-sialidase (rAdTS) T. cruzi antigens. For prophylactic vaccination, naive ...


The Genetics Of Hepatitis C Virus Underlie Its Ability To Escape Humoral Immunity, Jay K. Kolls, Gyongyi Szabo 2015 University of Pittsburgh

The Genetics Of Hepatitis C Virus Underlie Its Ability To Escape Humoral Immunity, Jay K. Kolls, Gyongyi Szabo

University of Massachusetts Medical School Faculty Publications

Hepatitis C virus (HCV) is a leading cause of chronic liver disease, and efforts to develop therapeutic vaccine strategies have been limited by immune escape due to HCV variants that are resistant to current vaccines or HCV variants that rapidly acquire new resistance-conferring mutations. Recently, the crystal structure of the viral envelope protein E2 region was resolved as well as how E2 docks to the host CD81 protein; therefore, antibodies that block this interaction should prevent viral entry into host cells. In this issue of the JCI, Bailey and colleagues show that immune escape of HCV can occur by naturally ...


Managing Devil Facial Tumour Disease In Tasmanian Devils (Sarcophilus Harrisii): An Investigation Of Heat Shock Proteins As Potential Vaccine Adjuvants, Monika Payerhin 2014 SIT Study Abroad

Managing Devil Facial Tumour Disease In Tasmanian Devils (Sarcophilus Harrisii): An Investigation Of Heat Shock Proteins As Potential Vaccine Adjuvants, Monika Payerhin

Independent Study Project (ISP) Collection

The world’s largest carnivorous marsupial, the Tasmanian devil (Sarcophilus harrisii), is facing extinction from a deadly, highly communicable cancer that has already decimated over 85% of devil populations in the wild: devil facial tumour disease (DFTD). DFTD cells effectively evade recognition by the immune system, and every devil that contracts the disease dies from it. Many attempts have been made at developing a vaccine that could help save this now-threatened species. Heat shock proteins have been linked to enhanced immune recognition of pathogens, making them potential candidates for acting as adjuvants to such a vaccine against DFTD. In this ...


Allele-Specific Induction Of Il-1beta Expression By C/Ebpbeta And Pu.1 Contributes To Increased Tuberculosis Susceptibility, Guoliang Zhang, Boping Zhou, Shaoyuan Li, Jun Yue, Hui Yang, Yuxin Wen, Senlin Zhan, Wenfei Wang, Mingfeng Liao, Mingxia Zhang, Gucheng Zeng, Carl G. Feng, Christopher M. Sassetti, Xinchun Chen 2014 Guangdong Medical College

Allele-Specific Induction Of Il-1beta Expression By C/Ebpbeta And Pu.1 Contributes To Increased Tuberculosis Susceptibility, Guoliang Zhang, Boping Zhou, Shaoyuan Li, Jun Yue, Hui Yang, Yuxin Wen, Senlin Zhan, Wenfei Wang, Mingfeng Liao, Mingxia Zhang, Gucheng Zeng, Carl G. Feng, Christopher M. Sassetti, Xinchun Chen

Open Access Articles

Mycobacterium tuberculosis infection is associated with a spectrum of clinical outcomes, from long-term latent infection to different manifestations of progressive disease. Pro-inflammatory pathways, such as those controlled by IL-1beta, have the contrasting potential both to prevent disease by restricting bacterial replication, and to promote disease by inflicting tissue damage. Thus, the ultimate contribution of individual inflammatory pathways to the outcome of M. tuberculosis infection remains ambiguous. In this study, we identified a naturally-occurring polymorphism in the human IL1B promoter region, which alters the association of the C/EBPbeta and PU.1 transcription factors and controls Mtb-induced IL-1beta production. The high-IL-1beta ...


Evaluation Of Naturally Acquired Igg Antibodies To A Chimeric And Non-Chimeric Recombinant Species Of Plasmodium Vivax Reticulocyte Binding Protein-1: Lack Of Association With Hla-Drb1*/Dqb1* In Malaria Exposed Individuals From The Brazilian Amazon, Amanda Ribeiro Ferreira, Balwan Singh, Monica Cabrera-Mora, Alana Cristina Magri De Souza, Maria Teresa Queiroz Marques, Luis Cristovao Sobrino Porto, Fatima Santos, Dalma Maria Banic, J. Mauricio Calvo-Calle, Joseli Oliveira-Ferreira, Alberto Moreno, Josue Da Costa Lima-Junior 2014 Oswaldo Cruz Institute

Evaluation Of Naturally Acquired Igg Antibodies To A Chimeric And Non-Chimeric Recombinant Species Of Plasmodium Vivax Reticulocyte Binding Protein-1: Lack Of Association With Hla-Drb1*/Dqb1* In Malaria Exposed Individuals From The Brazilian Amazon, Amanda Ribeiro Ferreira, Balwan Singh, Monica Cabrera-Mora, Alana Cristina Magri De Souza, Maria Teresa Queiroz Marques, Luis Cristovao Sobrino Porto, Fatima Santos, Dalma Maria Banic, J. Mauricio Calvo-Calle, Joseli Oliveira-Ferreira, Alberto Moreno, Josue Da Costa Lima-Junior

Open Access Articles

The development of modular constructs that include antigenic regions targeted by protective immune responses is an attractive approach for subunit vaccine development. However, a main concern of using these vaccine platforms is how to preserve the antigenic identity of conformational B cell epitopes. In the present study we evaluated naturally acquired antibody responses to a chimeric protein engineered to contain a previously defined immunodominant domain of the Plasmodium vivax reticulocyte binding protein-1 located between amino acid positions K435-I777. The construct also includes three regions of the cognate protein (F571-D587, I1745-S1786 and L2235-E2263) predicted to contain MHC class II promiscuous T ...


The Hunt For Protective Correlates Of Immunity To Plasmodium Falciparum Malaria, Ann M. Moormann, V. Ann Stewart 2014 University of Massachusetts Medical School

The Hunt For Protective Correlates Of Immunity To Plasmodium Falciparum Malaria, Ann M. Moormann, V. Ann Stewart

Open Access Articles

Determining an immunologic correlate of protection against Plasmodium falciparum malaria has been the holy grail of natural infection studies, and sought after as an endpoint for malaria vaccine trials. An in vitro assay that provides an accurate and precise assessment of protective immunity to malaria would make smaller, short-duration studies feasible, rather than the currently powered study designs that use morbidity or mortality as outcomes. Such a biomarker would be especially desirable in situations where malaria control measures that result in decreases in clinical endpoints and putatively waning protective immunity have been implemented. In an article published in BMC Medicine ...


An Unstable Th Epitope Of P. Falciparum Fosters Central Memory T Cells And Anti-Cs Antibody Responses, Carlos A. Parra-Lopez, David Bernal -Estevez, Luis Eduardo Eduardo Vargas, Carolina Pulido -Calixto, Luz Mary Salazar, J. Mauricio Calvo-Calle, Lawrence J. Stern 2014 Universidad Nacional de Colombia

An Unstable Th Epitope Of P. Falciparum Fosters Central Memory T Cells And Anti-Cs Antibody Responses, Carlos A. Parra-Lopez, David Bernal -Estevez, Luis Eduardo Eduardo Vargas, Carolina Pulido -Calixto, Luz Mary Salazar, J. Mauricio Calvo-Calle, Lawrence J. Stern

University of Massachusetts Medical School Faculty Publications

Malaria is transmitted by Plasmodium-infected anopheles mosquitoes. Widespread resistance of mosquitoes to insecticides and resistance of parasites to drugs highlight the urgent need for malaria vaccines. The most advanced malaria vaccines target sporozoites, the infective form of the parasite. A major target of the antibody response to sporozoites are the repeat epitopes of the circumsporozoite (CS) protein, which span almost one half of the protein. Antibodies to these repeats can neutralize sporozoite infectivity. Generation of protective antibody responses to the CS protein (anti-CS Ab) requires help by CD4 T cells. A CD4 T cell epitope from the CS protein designated ...


Protective Immunity And Safety Of A Genetically Modified Influenza Virus Vaccine, Rafael Polidoro Alves Barbosa, Ana Paula Carneiro Salgado, Cristiana Couto Garcia, Bruno Galvao Filho, Ana Paula de Faria Paula de Faria Goncalves, Braulio Henrique Freire Lima, Gabriel Augusto Oliveira Lopes, Milene Alvarenga Rachid, Andiara Cristina Cardoso Peixoto, Danilo Bretas de Oliveira, Marco Antonio Ataide, Carla Aparecida Zirke, Tatiane Marques Cotrim, Erica Azevedo Costa, Gabriel Magno de Freitas Almeida, Remo Castro Russo, Ricardo T. Gazzinelli, Alexandre de Magalhaes Vieira Machado 2014 Universidade Federal de Minas Gerais

Protective Immunity And Safety Of A Genetically Modified Influenza Virus Vaccine, Rafael Polidoro Alves Barbosa, Ana Paula Carneiro Salgado, Cristiana Couto Garcia, Bruno Galvao Filho, Ana Paula De Faria Paula De Faria Goncalves, Braulio Henrique Freire Lima, Gabriel Augusto Oliveira Lopes, Milene Alvarenga Rachid, Andiara Cristina Cardoso Peixoto, Danilo Bretas De Oliveira, Marco Antonio Ataide, Carla Aparecida Zirke, Tatiane Marques Cotrim, Erica Azevedo Costa, Gabriel Magno De Freitas Almeida, Remo Castro Russo, Ricardo T. Gazzinelli, Alexandre De Magalhaes Vieira Machado

University of Massachusetts Medical School Faculty Publications

Recombinant influenza viruses are promising viral platforms to be used as antigen delivery vectors. To this aim, one of the most promising approaches consists of generating recombinant viruses harboring partially truncated neuraminidase (NA) segments. To date, all studies have pointed to safety and usefulness of this viral platform. However, some aspects of the inflammatory and immune responses triggered by those recombinant viruses and their safety to immunocompromised hosts remained to be elucidated. In the present study, we generated a recombinant influenza virus harboring a truncated NA segment (vNA-Delta) and evaluated the innate and inflammatory responses and the safety of this ...


Circulating Levels Of Soluble Micb In Infants With Symptomatic Primary Dengue Virus Infections, Daniel H. Libraty, Lei Zhang, AnaMae Obcena, Job D. Brion, Rosario Z. Capeding 2014 University of Massachusetts Medical School

Circulating Levels Of Soluble Micb In Infants With Symptomatic Primary Dengue Virus Infections, Daniel H. Libraty, Lei Zhang, Anamae Obcena, Job D. Brion, Rosario Z. Capeding

University of Massachusetts Medical School Faculty Publications

Dengue is the most prevalent arthropod-borne viral illness in humans. A MHC class I polypeptide-related sequence B (MICB) single nucleotide polymorphism (SNP) was previously associated with symptomatic dengue compared to non-dengue causes of acute febrile illnesses in infants. We measured circulating levels of soluble (s)MICB in the sera of infants with symptomatic primary dengue virus infections. We found that serum levels of sMICB increased between pre-infection and acute illness among infants with symptomatic primary dengue virus infections. The likelihood of being hospitalized with an acute primary DENV infection during infancy also tended to be higher with increasing acute illness ...


Topical Anti-Tnf-Α Antibody Enhances Wound Healing In Diabetic Mice, Genevieve Broderick, Heather M. Strom, Ronald A. Ignotz 2014 University of Massachusetts Medical School

Topical Anti-Tnf-Α Antibody Enhances Wound Healing In Diabetic Mice, Genevieve Broderick, Heather M. Strom, Ronald A. Ignotz

UMass Center for Clinical and Translational Science Research Retreat

Chronic wounds such as venous leg ulcers and diabetic foot ulcers represent a significant health problem for which current treatment options are limited and not highly effective. These wounds have major impacts on the quality of life for affected individuals, frequently lead to amputation, and cost many thousands of dollars per year to treat. Assessment of wound fluid from such wounds indicates greatly elevated and persistently high levels of inflammatory cytokines, in particular Tumor Necrosis Factor-alpha (TNF-α). As such, these wounds are not in a physiologic state conducive to healing. Our study in diabetic mice (db/db) suggests that topical ...


Targeted Mutagenesis Of A Therapeutic Human Monoclonal Igg1 Antibody Prevents Gelation At High Concentrations, Paul Casaz, Elisabeth N. Boucher, Rachel Wollacott, Sadettin S. Ozturk, William D. Thomas Jr., Yan Wang 2014 University of Massachusetts Medical School

Targeted Mutagenesis Of A Therapeutic Human Monoclonal Igg1 Antibody Prevents Gelation At High Concentrations, Paul Casaz, Elisabeth N. Boucher, Rachel Wollacott, Sadettin S. Ozturk, William D. Thomas Jr., Yan Wang

UMass Center for Clinical and Translational Science Research Retreat

A common challenge encountered during development of high concentration monoclonal antibody formulations is preventing self-association. Depending on the antibody and its formulation, self-association can be seen as aggregation, precipitation, opalescence or phase separation. Here we report on an unusual manifestation of self-association, formation of a semi-solid gel or “gelation”. Therapeutic monoclonal antibody C4 was isolated from human B cells based on its strong potency in neutralizing bacterial toxin in animal models. The purified antibody possessed the unusual property of forming a firm, opaque white gel when it was formulated at concentrations >40 mg/mL and the temperature was <6oC. Gel formation was reversible and was affected by salt concentration or pH, suggesting a charge interaction between IgG monomers. However, formulation optimization could not completely prevent gelation at high concentrations so a protein engineering approach was sought to resolve the problem. A comparison of the heavy and light chain amino acid sequences to consensus germline sequences revealed 16 amino acid sequence differences in the framework regions that could be involved with gelation. Restoring the C4 framework sequence to consensus germline residues by targeted mutagenesis resulted in no gel formation at 50 mg/ml at temperatures as low as 0oC. Additional genetic analysis was used to identify the key residue(s) involved in the gelation. A single substitution in the native antibody, replacing heavy chain glutamate 23 with lysine, was found sufficient to prevent gelation, while a double mutation, replacing heavy chain serine 85 and threonine 87 with arginine, increased the temperature at which gel formation initiated. These results indicate that the temperature dependence of gelation may be related to conformational changes near the charged residues or the regions interact with. Our work provided a molecular strategy that can be applied to improve the solubility of other therapeutic antibodies.


Therapeutic Monoclonal Antibodies To Prevent Tuberculosis Infection, Andrew Crowley, Chloe Emery, Gregory W. Martens, Megan K. Proulx, Jon D. Goguen, Christopher M. Sassetti, Colby A. Souders 2014 University of Massachusetts Medical School

Therapeutic Monoclonal Antibodies To Prevent Tuberculosis Infection, Andrew Crowley, Chloe Emery, Gregory W. Martens, Megan K. Proulx, Jon D. Goguen, Christopher M. Sassetti, Colby A. Souders

UMass Center for Clinical and Translational Science Research Retreat

Mycobacteria tuberculosis (Mtb) is a major cause of human morbidity and mortality. Transmission occurs through inhalation of aerosolized Mtb and the initial infection is believed to occur primarily in the alveolar macrophage, although Mtb can infect other cells residing in the lung including dendritic cells, pneumocytes and M cells. Several molecules derived from Mtb are involved in the attachment of the organism to host receptors (opsonic and non-opsonic), which have been reasonably well elucidated. However, a complete understanding of how Mtb attaches to the host and the relative importance of each mechanism on the outcome of infection remains elusive. We ...


Isolation Of Human Antigen-Specific Antibodies From Memory B-Cells Nearly Two Years Post Vaccination, Stuart Nelson, Andrew Crowley, William D. Thomas Jr., Colby A. Souders 2014 University of Massachusetts Medical School

Isolation Of Human Antigen-Specific Antibodies From Memory B-Cells Nearly Two Years Post Vaccination, Stuart Nelson, Andrew Crowley, William D. Thomas Jr., Colby A. Souders

UMass Center for Clinical and Translational Science Research Retreat

Isolation and production of therapeutic human monoclonal antibodies (mAbs) traditionally utilizes a handful of techniques including antibody engineering, phage display, hybridoma generation from transgenic mice or EBV immortalization of B-cells. Over the past decade a new approach has emerged that attempts to extract antigen-specific memory B-cells from the peripheral blood of individuals vaccinated or infected with the target. Initial attempts focused on culturing B-cells and inducing differentiation to plasmablasts for analysis of antibody-antigen specificity, but results were largely mixed due to difficult culture conditions and/or rarity of target cells. With advancing technology in cell sorting, single antigen-specific memory B-cells ...


Structure-Based Design Of Broadly Neutralizing Hcv Antibody And Vaccine, Brian G. Pierce, Elisabeth N. Boucher, Heidi L. Smith, William D. Thomas Jr., Zhiping Weng, Yang Wang 2014 University of Massachusetts Medical School

Structure-Based Design Of Broadly Neutralizing Hcv Antibody And Vaccine, Brian G. Pierce, Elisabeth N. Boucher, Heidi L. Smith, William D. Thomas Jr., Zhiping Weng, Yang Wang

UMass Center for Clinical and Translational Science Research Retreat

Hepatitis C virus (HCV) chronically infects nearly 200 million people worldwide. Antibodies have the potential to prevent establishment of chronic HCV infection in individuals exposed to the virus. Several broadly neutralizing monoclonal antibodies capable of binding HCV surface glycoproteins have been identified, including HCV1 identified by MassBiologics at UMMS, which targets a highly conserved linear epitope. We utilized the recently solved structure of the HCV1-bound epitope to identify regions of the antibody that could be modified to potentially improve binding to a mutation (N415K) which facilitates escape from neutralization. Based on systematic in silico mutagenesis of HCV1 residues in the ...


Detection Of Cd8+ T Cell Responses In Individuals With Long-Term Type 1 Diabetes And Generation Of Human Cd8+ T Cell Lines Specific To Islet-Associated Autoantigens, Jenny Aurielle B. Babon, David M. Harlan, Sally C. Kent 2014 University of Massachusetts Medical School

Detection Of Cd8+ T Cell Responses In Individuals With Long-Term Type 1 Diabetes And Generation Of Human Cd8+ T Cell Lines Specific To Islet-Associated Autoantigens, Jenny Aurielle B. Babon, David M. Harlan, Sally C. Kent

UMass Center for Clinical and Translational Science Research Retreat

Type 1 diabetes (T1D) is an autoimmune disease characterized by the activation of lymphocytes against insulin-producing β-cells in the pancreas. In humans, CD8+ T cells are predominantly found in sites of insulitis and are considered to be one of the main drivers of β-cell destruction, thus indicating the need to analyze the frequency and function of these autoreactive CD8+ T cells. Peripheral blood mononuclear cells (PBMC) from individuals with long-term T1D were stained ex vivo for T cell surface markers and HLA-A2 pentamers containing known islet-associated epitopes to determine if there are autoreactive CD8+ T cells circulating in the periphery ...


Anti-Ppkcθ (T538) Delivery Via Cell Penetrating Peptide Mimics As A Novel Treatment Of Aplastic Anemia, Emrah Ilker Ozay, Gabriela Gonzalez-Perez, Joe Torres, Gregory N. Tew, Lisa M. Minter 2014 University of Massachusetts Amherst

Anti-Ppkcθ (T538) Delivery Via Cell Penetrating Peptide Mimics As A Novel Treatment Of Aplastic Anemia, Emrah Ilker Ozay, Gabriela Gonzalez-Perez, Joe Torres, Gregory N. Tew, Lisa M. Minter

UMass Center for Clinical and Translational Science Research Retreat

The objective of this study is to deliver anti-pPKCθ (T538) into T cells (hPBMCs) by using cell penetrating peptide mimics (CPPMs) to neutralize PKCθ activity both in vitro and in vivo, with the eventual goal of treating aplastic anemia (AA). AA is an immune-mediated bone marrow failure disease caused by T helper type 1 (Th1) autoimmune responses, which destroy blood cell progenitors. It was previously reported that protein kinase C theta (PKCθ), expressed specifically in T cells, plays an important role in T cell signaling by mediating Th1 differentiation. Mice treated with Rottlerin, a pharmacological inhibitor of PKCθ, are rescued ...


Developing A Whole Plant Artemisia Annua Antimalarial Therapeutic: Pact, Pamela Weathers, Nicole Jordan, Praphapan Lasin, Melissa Towler, Douglas T. Golenbock, Mostafa Elfawal, Nicholas Reich, George Acquaah-Mensah, Stephen Rich 2014 Worcester Polytechnic Institute

Developing A Whole Plant Artemisia Annua Antimalarial Therapeutic: Pact, Pamela Weathers, Nicole Jordan, Praphapan Lasin, Melissa Towler, Douglas T. Golenbock, Mostafa Elfawal, Nicholas Reich, George Acquaah-Mensah, Stephen Rich

UMass Center for Clinical and Translational Science Research Retreat

The GRAS plant Artemisia annua L. produces the sesquiterpene lactone, artemisinin. The current therapy for malaria is artemisinin + an older drug: artemisinin combination therapy (ACT). In Plasmodium chabaudi-infected mice, dried leaves of A. annua are more potent than equal amounts of pure artemisinin and may also prevent artemisinin drug resistance from emerging. This whole plant therapy is pACT: plant-based artemisinin combination therapy. Pharmacokinetics in healthy and infected mice given either pure artemisinin or pACT is different and showed that > 40 fold more artemisinin enters the blood when plant material is present; plant matrix enhanced bioavailability into serum. Dried leaves as ...


Use Of Cholera Toxin B As A Vaccine Adjuvant Activates Antigen Presenting Cells And Stimulates Production Of Pro-Inflammatory Cytokines, Heather C. Romlein 2014 Seton Hall University

Use Of Cholera Toxin B As A Vaccine Adjuvant Activates Antigen Presenting Cells And Stimulates Production Of Pro-Inflammatory Cytokines, Heather C. Romlein

Seton Hall University Dissertations and Theses (ETDs)

Francisella tularensis is an intracellular pathogen that has been classified as a category “A” bioterrorism agent by the Centers For Disease Control. To date, there is no approved vaccine to provide protection against this pathogen. Previous in vivo studies with mice have shown that a mucosally targeted vaccine preparation of inactivated F. tularensis (iFt) adjuvanted with Cholera toxin “B” (CTB), successfully granted full protection against a less virulent strain (FT LVS) of the bacterium and provided partial protection against a more virulent strain (SchuS4). However, the mechanisms of this protection are not fully understood. In this present study, an in ...


Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer 2014 University of Connecticut - Storrs

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

Honors Scholar Theses

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed ...


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