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Immunoprophylaxis and Therapy Commons

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Intron-Containing Rna From The Hiv-1 Provirus Activates Type I Interferon And Inflammatory Cytokines, Sean M. McCauley, Kyusik Kim, Anetta Nowosielska, Ann Dauphin, Leonid Yurkovetskiy, William E. Diehl, Jeremy Luban 2018 University of Massachusetts Medical School

Intron-Containing Rna From The Hiv-1 Provirus Activates Type I Interferon And Inflammatory Cytokines, Sean M. Mccauley, Kyusik Kim, Anetta Nowosielska, Ann Dauphin, Leonid Yurkovetskiy, William E. Diehl, Jeremy Luban

Program in Molecular Medicine Publications and Presentations

HIV-1-infected people who take drugs that suppress viremia to undetectable levels are protected from developing AIDS. Nonetheless, these individuals have chronic inflammation associated with heightened risk of cardiovascular pathology. HIV-1 establishes proviruses in long-lived CD4+ memory T cells, and perhaps other cell types, that preclude elimination of the virus even after years of continuous antiviral therapy. Though the majority of proviruses that persist during antiviral therapy are defective for production of infectious virions, many are expressed, raising the possibility that the HIV-1 provirus or its transcripts contribute to ongoing inflammation. Here we found that the HIV-1 provirus activated innate immune ...


Tumor Surveillance Using Liquid Biome In Pediatric High Grade Gliomas, Erin Bonner, Eshini Panditharatna, Madhuri Kambhampati, Stefaan Van Gool, Wilfried Stuecker, Roger J. Packer, Javad Nazarian 2018 Children's National Health System

Tumor Surveillance Using Liquid Biome In Pediatric High Grade Gliomas, Erin Bonner, Eshini Panditharatna, Madhuri Kambhampati, Stefaan Van Gool, Wilfried Stuecker, Roger J. Packer, Javad Nazarian

GW Research Days 2016 - Present

Immunotherapy is currently being used to treat pediatric brain cancer, though its efficacy in treating patients with diffuse intrinsic pontine glioma (DIPG), the deadliest pediatric brain tumor, has not been evaluated. MRI is the gold standard for monitoring tumor response to therapy, but is limited by pseudoresponse and psuedoprogression: post-treatment, immune cells infiltrate the primary tumor causing transient tumor enlargement, which falsely resembles tumor progression on MRI. Thus, it is critical to develop more accurate approaches to monitor tumor response to immunotherapy. Here, we use a liquid biopsy platform we have already established to monitor tumor response to therapy, to ...


New Vaccine Formulations Containing A Modified Version Of The Amastigote 2 Antigen And The Non-Virulent Trypanosoma Cruzi Cl-14 Strain Are Highly Antigenic And Protective Against Leishmania Infantum Challenge, Ana Paula M. M. Almeida, Leopoldo F.M. Machado, Daniel Doro, Frederico C. Nascimento, Leonardo Damasceno, Ricardo T. Gazzinelli, Ana Paula Fernandes, Caroline Junqueira 2018 Federal University of Minas Gerais

New Vaccine Formulations Containing A Modified Version Of The Amastigote 2 Antigen And The Non-Virulent Trypanosoma Cruzi Cl-14 Strain Are Highly Antigenic And Protective Against Leishmania Infantum Challenge, Ana Paula M. M. Almeida, Leopoldo F.M. Machado, Daniel Doro, Frederico C. Nascimento, Leonardo Damasceno, Ricardo T. Gazzinelli, Ana Paula Fernandes, Caroline Junqueira

Open Access Articles

Visceral leishmaniasis (VL) is a major public health issue reported as the second illness in mortality among all tropical diseases. Clinical trials have shown that protection against VL is associated with robust T cell responses, especially those producing IFN-gamma. The Leishmania amastigote 2 (A2) protein has been repeatedly described as immunogenic and protective against VL in different animal models; it is recognized by human T cells, and it is also commercially available in a vaccine formulation containing saponin against canine VL. Moving toward a more appropriate formulation for human vaccination, here, we tested a new optimized version of the recombinant ...


Humanized Mice In Studying Efficacy And Mechanisms Of Pd-1-Targeted Cancer Immunotherapy, Minan Wang, Michael A. Brehm, Dale L. Greiner 2018 The Jackson Laboratory

Humanized Mice In Studying Efficacy And Mechanisms Of Pd-1-Targeted Cancer Immunotherapy, Minan Wang, Michael A. Brehm, Dale L. Greiner

Open Access Articles

Establishment of an in vivo small animal model of human tumor and human immune system interaction would enable preclinical investigations into the mechanisms underlying cancer immunotherapy. To this end, nonobese diabetic (NOD).Cg- Prkdc(scid)IL2rg(tm1Wjl)/Sz (null; NSG) mice were transplanted with human (h)CD34(+) hematopoietic progenitor and stem cells, which leads to the development of human hematopoietic and immune systems [humanized NSG (HuNSG)]. HuNSG mice received human leukocyte antigen partially matched tumor implants from patient-derived xenografts [PDX; non-small cell lung cancer (NSCLC), sarcoma, bladder cancer, and triple-negative breast cancer (TNBC)] or from a TNBC cell line-derived xenograft ...


Use Of Elispot Assay To Study Hbs-Specific B Cell Responses In Vaccinated And Hbv Infected Humans, Chen Tian, Yuxin Chen, Yong Liu, Shixia Wang, Yang Li, Guiyang Wang, Juan Xia, Xiang-An Zhao, Rui Huang, Shan Lu, Chao Wu 2018 Nanjing University

Use Of Elispot Assay To Study Hbs-Specific B Cell Responses In Vaccinated And Hbv Infected Humans, Chen Tian, Yuxin Chen, Yong Liu, Shixia Wang, Yang Li, Guiyang Wang, Juan Xia, Xiang-An Zhao, Rui Huang, Shan Lu, Chao Wu

Open Access Articles

Hepatitis B surface antibody (HBsAb) plays a critical role in protecting against infection of hepatitis B virus (HBV) and were extensively studied in literature. At the same time, the status of hepatitis B surface antigen (HBs)-specific B cells in both vaccinated and HBV infected people received limited attention. In the current study, we adopted a highly specific B-cell Enzyme Linked ImmunoSpot (ELISpot) assay to analyze HBs-specific B cells in various clinical settings: healthy individuals with the history of HBV vaccination before and after receiving an extra HBV vaccine boost, people chronically infected with HBV (CHB) in various clinical stages ...


New Gorilla Adenovirus Vaccine Vectors Induce Potent Immune Responses And Protection In A Mouse Malaria Model, Keith Limbach, Ann M. Moormann, Joseph T. Bruder 2018 Naval Medical Research Center

New Gorilla Adenovirus Vaccine Vectors Induce Potent Immune Responses And Protection In A Mouse Malaria Model, Keith Limbach, Ann M. Moormann, Joseph T. Bruder

Ann M. Moormann

BACKGROUND: A DNA-human Ad5 (HuAd5) prime-boost malaria vaccine has been shown to protect volunteers against a controlled human malaria infection. The potency of this vaccine, however, appeared to be affected by the presence of pre-existing immunity against the HuAd5 vector. Since HuAd5 seroprevalence is very high in malaria-endemic areas of the world, HuAd5 may not be the most appropriate malaria vaccine vector. This report describes the evaluation of the seroprevalence, immunogenicity and efficacy of three newly identified gorilla adenoviruses, GC44, GC45 and GC46, as potential malaria vaccine vectors.

RESULTS: The seroprevalence of GC44, GC45 and GC46 is very low, and ...


Hiv-1 R5 Macrophage-Tropic Envelope Glycoprotein Trimers Bind Cd4 With High Affinity, While The Cd4 Binding Site On Non-Macrophage-Tropic, T-Tropic R5 Envelopes Is Occluded, Briana Quitadamo, Paul J. Peters, Alexander Repik, Olivia O'Connell, Zhongming Mou, Matthew Koch, Mohan Somasundaran, Robin M. Brody, Katherine Luzuriaga, Aaron Wallace, Shixia Wang, Shan Lu, Sean M. McCauley, Jeremy Luban, Maria J. Duenas-Decamp, Maria Paz Paz Gonzalez-Perez, Paul R. Clapham 2018 University of Massachusetts Medical School

Hiv-1 R5 Macrophage-Tropic Envelope Glycoprotein Trimers Bind Cd4 With High Affinity, While The Cd4 Binding Site On Non-Macrophage-Tropic, T-Tropic R5 Envelopes Is Occluded, Briana Quitadamo, Paul J. Peters, Alexander Repik, Olivia O'Connell, Zhongming Mou, Matthew Koch, Mohan Somasundaran, Robin M. Brody, Katherine Luzuriaga, Aaron Wallace, Shixia Wang, Shan Lu, Sean M. Mccauley, Jeremy Luban, Maria J. Duenas-Decamp, Maria Paz Paz Gonzalez-Perez, Paul R. Clapham

Program in Molecular Medicine Publications and Presentations

HIV-1 R5 variants exploit CCR5 as a coreceptor to infect both T cells and macrophages. R5 viruses that are transmitted or derived from immune tissue and peripheral blood are mainly inefficient at mediating infection of macrophages. In contrast, highly macrophage-tropic (mac-tropic) R5 viruses predominate in brain tissue and can be detected in cerebrospinal fluid but are infrequent in immune tissue or blood even in late disease. These mac-tropic R5 variants carry envelope glycoproteins (Envs) adapted to exploit low levels of CD4 on macrophages to induce infection. However, it is unclear whether this adaptation is conferred by an increased affinity of ...


The Importance Of Rsv F Protein Conformation In Vlps In Stimulation Of Neutralizing Antibody Titers In Mice Previously Infected With Rsv, Lori M. Cullen, Madelyn R. Schmidt, Trudy G. Morrison 2017 University of Massachusetts Medical School

The Importance Of Rsv F Protein Conformation In Vlps In Stimulation Of Neutralizing Antibody Titers In Mice Previously Infected With Rsv, Lori M. Cullen, Madelyn R. Schmidt, Trudy G. Morrison

Open Access Articles

Respiratory syncytial virus (RSV) is a significant respiratory pathogen but no vaccine is available. RSV infections present 2 major, unique problems. First, humans can experience repeated infections caused by the same virus sero-group indicating that protective memory responses to RSV infection are defective. Second, most people have been infected with RSV by age 5. Immune responses to these infections, while poorly protective, could impact the effectiveness of a vaccine. The goal of this study was to assess the generation of protective immune responses in mice previously infected with RSV by virus-like particle (VLP) vaccine candidates containing a stabilized pre-fusion form ...


Screening Of Primary Gp120 Immunogens To Formulate The Next Generation Polyvalent Dna Prime-Protein Boost Hiv-1 Vaccines, Shixia Wang, Te-Hui Chou, Anthony Hackett, Veronica Efros, Yan Wang, Dong Han, Aaron Wallace, Yuxin Chen, Guangnan Hu, Shuying Liu, Paul R. Clapham, James Arthos, David Montefiori, Shan Lu 2017 University of Massachusetts Medical School

Screening Of Primary Gp120 Immunogens To Formulate The Next Generation Polyvalent Dna Prime-Protein Boost Hiv-1 Vaccines, Shixia Wang, Te-Hui Chou, Anthony Hackett, Veronica Efros, Yan Wang, Dong Han, Aaron Wallace, Yuxin Chen, Guangnan Hu, Shuying Liu, Paul R. Clapham, James Arthos, David Montefiori, Shan Lu

Open Access Articles

Our previous preclinical studies and a Phase I clinical trial DP6-001 have indicated that a polyvalent Env formulation was able to elicit broadly reactive antibody responses including low titer neutralizing antibody responses against viral isolates of subtypes A, B, C and AE. In the current report, a panel of 62 gp120 immunogens were screened in a rabbit model to identify gp120 immunogens that can elicit improved binding and neutralizing antibody responses and some of them can be included in the next polyvalent formulation. Only about 19% of gp120 immunogens in this panel were able to elicit neutralizing antibodies against greater ...


The Dynamics Of Immunoglobulin V-Gene Usage And Clonotype Expansion In Mice After Prime And Boost Immunizations As Analyzed By Ngs, Diego José Farfán Arribas, Shuying Liu, Shixia Wang, Shan Lu 2017 University of Massachusetts Medical School

The Dynamics Of Immunoglobulin V-Gene Usage And Clonotype Expansion In Mice After Prime And Boost Immunizations As Analyzed By Ngs, Diego José Farfán Arribas, Shuying Liu, Shixia Wang, Shan Lu

Open Access Articles

In the current study, an improved NGS approach was developed to study the B-cell repertoire evolution in a simple mouse immunization model including only two DNA immunizations. The combination of 5'RACE and Ion Torrent long reads enabled unbiased immunoglobulin repertoire analysis even from small amounts of peripheral mouse blood. The B-cell population expanded by the vaccine displayed a relatively strong clonality. Upon priming with the first vaccine dose, we observed a consistent pattern of V-segment gene and CDR3 usage (public specificities). Interestingly, this pattern diversified with the second dose of immunization -it was relatively different in individual mice in ...


Recombinant Subunit Vaccines For Soil-Transmitted Helminths, Jason B. Noon, Raffi V. Aroian 2017 University of Massachusetts Medical School

Recombinant Subunit Vaccines For Soil-Transmitted Helminths, Jason B. Noon, Raffi V. Aroian

Open Access Articles

Soil-transmitted helminths (STHs) collectively infect one fourth of all human beings, and the majority of livestock in the developing world. These gastrointestinal nematodes are the most important parasites on earth with regard to their prevalence in humans and livestock. Current anthelmintic drugs are losing their efficacies due to increasing drug resistance, particularly in STHs of livestock and drug treatment is often followed by rapid reinfection due to failure of the immune system to develop a protective response. Vaccines against STHs offer what drugs cannot accomplish alone. Because such vaccines would have to be produced on such a large scale, and ...


Vaccination With Recombinant Cryptococcus Proteins In Glucan Particles Protects Mice Against Cryptococcosis In A Manner Dependent Upon Mouse Strain And Cryptococcal Species, Charles A. Specht, Chrono K. Lee, Haibin Huang, Maureen M. Hester, Jianhua Liu, Bridget A. Luckie, Melanie A. Torres Santana, Zeynep Mirza, Payam Khoshkenar, Ambily Abraham, Zu T. Shen, Ali Akalin, Gary R. Ostroff, Stuart M. Levitz 2017 University of Massachusetts Medical School

Vaccination With Recombinant Cryptococcus Proteins In Glucan Particles Protects Mice Against Cryptococcosis In A Manner Dependent Upon Mouse Strain And Cryptococcal Species, Charles A. Specht, Chrono K. Lee, Haibin Huang, Maureen M. Hester, Jianhua Liu, Bridget A. Luckie, Melanie A. Torres Santana, Zeynep Mirza, Payam Khoshkenar, Ambily Abraham, Zu T. Shen, Ali Akalin, Gary R. Ostroff, Stuart M. Levitz

Open Access Articles

Development of a vaccine to protect against cryptococcosis is a priority given the enormous global burden of disease in at-risk individuals. Using glucan particles (GPs) as a delivery system, we previously demonstrated that mice vaccinated with crude Cryptococcus-derived alkaline extracts were protected against lethal challenge with Cryptococcus neoformans and Cryptococcus gattii The goal of the present study was to identify protective protein antigens that could be used in a subunit vaccine. Using biased and unbiased approaches, six candidate antigens (Cda1, Cda2, Cda3, Fpd1, MP88, and Sod1) were selected, recombinantly expressed in Escherichia coli, purified, and loaded into GPs. Three mouse ...


Vaccine-Elicited Memory Cd4+ T Cell Expansion Is Impaired In The Lungs During Tuberculosis, Stephen M. Carpenter, Jason D. Yang, Jinhee Lee, Palmira Barreira-Silva, Samuel M. Behar 2017 University of Massachusetts Medical School

Vaccine-Elicited Memory Cd4+ T Cell Expansion Is Impaired In The Lungs During Tuberculosis, Stephen M. Carpenter, Jason D. Yang, Jinhee Lee, Palmira Barreira-Silva, Samuel M. Behar

Open Access Articles

Immunological memory is the key biological process that makes vaccines possible. Although tuberculosis vaccines elicit protective immunity in animals, few provide durable protection. To understand why protection is transient, we evaluated the ability of memory CD4+ T cells to expand, differentiate, and control Mycobacterium tuberculosis. Both naive and memory CD4+ T cells initially proliferated exponentially, and the accumulation of memory T cells in the lung correlated with early bacterial control. However, later during infection, memory CD4+ T cell proliferation was curtailed and no protection was observed. We show that memory CD4+ T cells are first activated in the LN and ...


Lfa-1 Mediates Cytotoxicity And Tissue Migration Of Specific Cd8(+) T Cells After Heterologous Prime-Boost Vaccination Against Trypanosoma Cruzi Infection, Camila Pontes Ferreira, Leonardo Moro. Cariste, Fernando Dos. Santos Virgilio, Barbara Ferri Moraschi, Caroline Brandao. Monteiro, Alexandre M. Vieira Machado, Ricardo T. Gazzinelli, Oscar Bruna-Romero, Pedro Luiz. Menin Ruiz, Daniel Araki Ribeiro, Joseli Lannes-Vieira, Marcela de Freitas Lopes, Mauricio Martins Rodrigues, Jose Ronnie. de Vasconcelos Carvalho 2017 Federal University of São Paulo

Lfa-1 Mediates Cytotoxicity And Tissue Migration Of Specific Cd8(+) T Cells After Heterologous Prime-Boost Vaccination Against Trypanosoma Cruzi Infection, Camila Pontes Ferreira, Leonardo Moro. Cariste, Fernando Dos. Santos Virgilio, Barbara Ferri Moraschi, Caroline Brandao. Monteiro, Alexandre M. Vieira Machado, Ricardo T. Gazzinelli, Oscar Bruna-Romero, Pedro Luiz. Menin Ruiz, Daniel Araki Ribeiro, Joseli Lannes-Vieira, Marcela De Freitas Lopes, Mauricio Martins Rodrigues, Jose Ronnie. De Vasconcelos Carvalho

Open Access Articles

Integrins mediate the lymphocyte migration into an infected tissue, and these cells are essential for controlling the multiplication of many intracellular parasites such as Trypanosoma cruzi, the causative agent of Chagas disease. Here, we explore LFA-1 and VLA-4 roles in the migration of specific CD8(+) T cells generated by heterologous prime-boost immunization during experimental infection with T. cruzi. To this end, vaccinated mice were treated with monoclonal anti-LFA-1 and/or anti-VLA-4 to block these molecules. After anti-LFA-1, but not anti-VLA-4 treatment, all vaccinated mice displayed increased blood and tissue parasitemia, and quickly succumbed to infection. In addition, there was an ...


Interpreting T-Cell Cross-Reactivity Through Structure: Implications For Tcr-Based Cancer Immunotherapy, Dinler A. Antunes, Mauricio M. Rigo, Martiela V. Freitas, Marcus F. A. Mendes, Marialva Sinigaglia, Gregory Lizee, Lydia E. Kavraki, Liisa K. Selin, Markus Cornberg, Gustavo F. Vieira 2017 Universidade Federal do Rio Grande do Sul

Interpreting T-Cell Cross-Reactivity Through Structure: Implications For Tcr-Based Cancer Immunotherapy, Dinler A. Antunes, Mauricio M. Rigo, Martiela V. Freitas, Marcus F. A. Mendes, Marialva Sinigaglia, Gregory Lizee, Lydia E. Kavraki, Liisa K. Selin, Markus Cornberg, Gustavo F. Vieira

Open Access Articles

Immunotherapy has become one of the most promising avenues for cancer treatment, making use of the patient's own immune system to eliminate cancer cells. Clinical trials with T-cell-based immunotherapies have shown dramatic tumor regressions, being effective in multiple cancer types and for many different patients. Unfortunately, this progress was tempered by reports of serious (even fatal) side effects. Such therapies rely on the use of cytotoxic T-cell lymphocytes, an essential part of the adaptive immune system. Cytotoxic T-cells are regularly involved in surveillance and are capable of both eliminating diseased cells and generating protective immunological memory. The specificity of ...


Structure-Based Design Of Hepatitis C Virus Vaccines That Elicit Neutralizing Antibody Responses To A Conserved Epitope, Brian G. Pierce, Elisabeth N. Boucher, Kurt H. Piepenbrink, Ejemel Monir, Chelsea A. Rapp, William D. Thomas Jr., Eric J. Sundberg, Zhiping Weng, Yan Wang 2017 University of Massachusetts Medical School

Structure-Based Design Of Hepatitis C Virus Vaccines That Elicit Neutralizing Antibody Responses To A Conserved Epitope, Brian G. Pierce, Elisabeth N. Boucher, Kurt H. Piepenbrink, Ejemel Monir, Chelsea A. Rapp, William D. Thomas Jr., Eric J. Sundberg, Zhiping Weng, Yan Wang

Program in Bioinformatics and Integrative Biology Publications and Presentations

Despite recent advances in therapeutic options, hepatitis C virus (HCV) remains a severe global disease burden, and a vaccine can substantially reduce its incidence. Due to its extremely high sequence variability, HCV can readily escape the immune response; thus, an effective vaccine must target conserved, functionally important epitopes. Using the structure of a broadly neutralizing antibody in complex with a conserved linear epitope from the HCV E2 envelope glycoprotein (residues 412 to 423; epitope I), we performed structure-based design of immunogens to induce antibody responses to this epitope. This resulted in epitope-based immunogens based on a cyclic defensin protein, as ...


Discovery Of Pf-06928215 As A High Affinity Inhibitor Of Cgas Enabled By A Novel Fluorescence Polarization Assay, Justin Hall, Douglas T. Golenbock, Eicke Latz 2017 Pfizer

Discovery Of Pf-06928215 As A High Affinity Inhibitor Of Cgas Enabled By A Novel Fluorescence Polarization Assay, Justin Hall, Douglas T. Golenbock, Eicke Latz

Open Access Articles

Cyclic GMP-AMP synthase (cGAS) initiates the innate immune system in response to cytosolic dsDNA. After binding and activation from dsDNA, cGAS uses ATP and GTP to synthesize 2', 3' -cGAMP (cGAMP), a cyclic dinucleotide second messenger with mixed 2'-5' and 3'-5' phosphodiester bonds. Inappropriate stimulation of cGAS has been implicated in autoimmune disease such as systemic lupus erythematosus, thus inhibition of cGAS may be of therapeutic benefit in some diseases; however, the size and polarity of the cGAS active site makes it a challenging target for the development of conventional substrate-competitive inhibitors. We report here the development of ...


Alcohol And Cancer: Mechanisms And Therapies, Anuradha Ratna, Pranoti Mandrekar 2017 University of Massachusetts Medical School

Alcohol And Cancer: Mechanisms And Therapies, Anuradha Ratna, Pranoti Mandrekar

Open Access Articles

Several scientific and clinical studies have shown an association between chronic alcohol consumption and the occurrence of cancer in humans. The mechanism for alcohol-induced carcinogenesis has not been fully understood, although plausible events include genotoxic effects of acetaldehyde, cytochrome P450 2E1 (CYP2E1)-mediated generation of reactive oxygen species, aberrant metabolism of folate and retinoids, increased estrogen, and genetic polymorphisms. Here, we summarize the impact of alcohol drinking on the risk of cancer development and potential underlying molecular mechanisms. The interactions between alcohol abuse, anti-tumor immune response, tumor growth, and metastasis are complex. However, multiple studies have linked the immunosuppressive effects ...


The Combined Effect Of Oseltamivir And Favipiravir On Influenza A Virus Evolution, Louise Ormond, Ping Liu, Sebastian Matuszewski, Nicholas Renzette, Claudia Bank, Konstantin B. Zeldovich, Daniel N. Bolon, Timothy F. Kowalik, Robert W. Finberg, Jeffrey D. Jensen, Jennifer P. Wang 2017 École Polytechnique Fédérale de Lausanne

The Combined Effect Of Oseltamivir And Favipiravir On Influenza A Virus Evolution, Louise Ormond, Ping Liu, Sebastian Matuszewski, Nicholas Renzette, Claudia Bank, Konstantin B. Zeldovich, Daniel N. Bolon, Timothy F. Kowalik, Robert W. Finberg, Jeffrey D. Jensen, Jennifer P. Wang

Open Access Articles

Influenza virus inflicts a heavy death toll annually and resistance to existing antiviral drugs has generated interest in the development of agents with novel mechanisms of action. Favipiravir is an antiviral drug that acts by increasing the genome-wide mutation rate of influenza A virus (IAV). Potential synergistic benefits of combining oseltamivir and favipiravir have been demonstrated in animal models of influenza, but the population-level effects of combining the drugs are unknown. In order to elucidate the underlying evolutionary processes at play, we performed genome-wide sequencing of IAV experimental populations subjected to serial passaging in vitro under a combined protocol of ...


Rational Drug Design Directed At Blocking The Initial Signaling Events In Lipopolysaccharide-Induced Sepsis., Christopher A. Tipton 2017 University of Missouri - St. Louis

Rational Drug Design Directed At Blocking The Initial Signaling Events In Lipopolysaccharide-Induced Sepsis., Christopher A. Tipton

Theses

Systemic Inflammatory Response Syndrome (SIRS) is classified as an immune system response to an infectious state. If left untreated, SIRS leads to sepsis, septic shock, end-organ dysfunction, and death. As a patient progresses through these stages, associations of acute respiratory distress, disseminated intravascular coagulation, and acute renal failure persist, resulting in millions of deaths annually. Lipopolysaccharide (LPS), a bacterial endotoxin, is released into the blood stream, triggering SIRS. LPS is found in the outer cell-wall of Gram-negative bacteria and is responsible for initiation of a devastating cytokine storm. One of the regions of LPS, lipid A, is a polyacylated glucosamine ...


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