Microbiology Commons^™

The Rhesus Macaque Model Of Mycobacterium Avium Infection Reveals That Age-Related Disease Is Due In Part To Chronic Inflammation And Lung Microbial Dysbiosis, Ethan G. Napier

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Aging is associated with dysregulated immunity and increased susceptibility to infection, a phenomenon dubbed as immunosenescence and characterized by reduced naïve T and B cell pools, altered innate immune function, and chronic low-grade inflammation. Nontuberculous mycobacterial (NTM) pulmonary disease (NTMPD) is an increasingly relevant chronic lung infection that disproportionately affects older adults (65+ years) and immunocompromised individuals. However, the host factors underlying increased disease severity in aged patients remain poorly defined. Literature suggests that effective control of NTM relies on coordinated innate and adaptive immune responses, particularly macrophage activation and Th1 cytokine signaling. Using a rhesus macaque model that closely …

Characterizing The Human Metapneumovirus Matrix Protein And Its Role In Infection, Chase J. Heim

Theses and Dissertations--Molecular and Cellular Biochemistry

Human metapneumovirus (HMPV) causes severe respiratory tract infections in all cohorts, but especially in vulnerable groups such as children, older adults, and the immunocompromised. The matrix (M) protein of HMPV, like the M proteins of other members of the Mononegavirales order, is involved in virus assembly and budding. However, other functions of the HMPV M protein have yet to be elucidated. To investigate these various functions of the M protein, we used a peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) antisense agent designed to block translation of the M gene to reduce M expression during infection. Treatment with varying concentrations of an …

Exploring Oxylipins In Host–Microbe Interactions And Their Impact On Infection And Immunity, Robert J. Neff, Christopher D. Radka

Markey Cancer Center Faculty Publications

Plasma lipids are essential components of biological systems, transported through interactions with proteins to maintain cellular functions. These lipids exist in various forms, such as fatty acids, glycerolipids, glycerophospholipids, sphingolipids, sterols, and prenol lipids, derived from dietary intake, adipose tissue, and biosynthesis. While the association between certain fatty acids and cardiovascular diseases has been widely recognized, polyunsaturated fatty acids (PUFAs) exhibit cardioprotective effects, reducing risks of arrhythmias and heart-related mortality. This is due to their role in the production of eicosanoids, which modulate inflammation. Chronic inflammation, particularly in obesity, is significantly influenced by fatty acids, with saturated fatty acids promoting …

Ddo-Adjuvanted Influenza A Virus Nucleoprotein Mrna Vaccine Induces Robust Humoral And Cellular Type 1 Immune Responses And Protects Mice From Challenge, Victoria Gnazzo, Hanaa Saleh, Ítalo A. Castro, Adrianus C. M. Boon, Amelia K. Pinto, James D. Brien, Carolina B. López

Markey Cancer Center Faculty Publications

A challenge in viral vaccine development is to produce vaccines that generate both neutralizing antibodies to prevent infection and cytotoxic CD8+ T-cells that target conserved viral proteins and can eliminate infected cells to control virus spread. mRNA technology offers an opportunity to design vaccines based on conserved CD8-targeting epitopes, but achieving robust antigen-specific CD8+ T-cells remains a challenge. Here, we tested the viral-derived oligonucleotide DDO268 as an adjuvant in the context of a model influenza A virus (IAV) nucleoprotein (NP) mRNA vaccine in C57BL/6 mice. DDO268 when co-packaged with mRNA in lipid nanoparticles is sensed by RIG I-like receptors and …

Clonal Variation In Effector Gene Expression As A Mechanism For Pathogenic Adaptation In Magnaporthe Oryzae, Rebekah J. Ellsworth

Theses and Dissertations--Plant Pathology

Magnaporthe oryzae is a filamentous fungal pathogen that causes destructive diseases in cereals, including rice blast, wheat blast, and gray leaf spot. It is responsible for 10–30% annual yield losses in rice (Nalley et al., 2016) and up to 100% loss in wheat under favorable conditions (Kohli et al., 2011). Disease management typically relies on the use of resistant cultivars, but M. oryzae rapidly overcomes host resistance by mutating or deleting avirulence (AVR) genes recognized by host immune receptors. This rapid adaptation, often occurring within one to two growing seasons, presents a major challenge to breeding for durable resistance.

The …

Spermidine And Polyamine Blockade As Key Mediators Of Intestinal Epithelial Cell Functions, Madison Lynn Flory

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Frequently, alterations in the composition of the gut microbiota and its metabolites are linked with intestinal diseases, including inflammatory bowel disease and colorectal cancer. However, the direct connections between alterations in the microbiome and disease states often remain elusive. Prior research has identified increases in both polyamines, which are a class of microbial metabolite, and in the abundance of bacteria that can produce polyamines, in a murine colorectal cancer model. Understanding the significance of the interaction between these microbial metabolites and intestinal epithelial cells (IECs) will provide new and expanded evidence of the importance of the gut microbiome in colorectal …

Investigating Regulation And The Regulome Of The Nucleic Acid Binding Protein Spovg Within Borrelia Burgdorferi, Timothy C. Saylor

Theses and Dissertations--Medical Sciences

Prior studies indicated Borrelia burgdorferi SpoVG protein was regulated, SpoVG binds specifically to a number of nucleic acids, and SpoVG binds to the non-variable section of the major virulence factor vlsE. Although a direct transcriptional activator or inhibitor was not elucidated, it is shown that SpoVG is regulated based on cell culture density independent of the growth rate of B. burgdorferi, indicating that SpoVG regulation is outside the scope of the alternative sigma factor RpoS. Using a dCas9 CRISPRi construct to target SpoVG resulted in protein expression trending towards upregulation of the BosR-RpoS regulon, and a marked decrease …

Valorizing Municipal Solid Waste For Sustainable Aviation Fuel And Polyhydroxyalkanoate Bioplastics: Pyrolysis And Microbial Pathways, Emon Das

Theses and Dissertations--Biosystems and Agricultural Engineering

The escalating global burden of municipal solid waste (MSW), projected to reach 3.88 billion tons annually by 2050, calls for innovative valorization strategies to mitigate environmental impacts and promote a circular bioeconomy. This thesis investigates the conversion of MSW into two high-value products: sustainable aviation fuel (SAF) and polyhydroxyalkanoate (PHA) bioplastics. Chapter one presents comprehensive physicochemical characterization and pyrolysis-GC/MS analysis of MSW feedstocks. The physicochemical results reveal that densification enhances handling and storage properties, while pyrolysis-GC/MS analysis indicates that plastic-rich MSW streams produce bio-oils with favorable hydrocarbon profiles suitable for SAF production, potentially contributing to decarbonization efforts in the aviation …

Characterizing Agroecosystem Effects Of Industrial Hemp On A Rotational Row Cropping System And Microbial Communities, Kent D. Pham

Theses and Dissertations--Plant and Soil Sciences

The implementation of crop rotation on a farm can have many benefits for agroecosystem health and production. This practice can potentially reduce nutrient amendments, disrupt pest and disease cycles, and increase crop yields. In Kentucky, one common rotation consists of either corn or soybean grown the first year, followed by the other crop, repeated every two years. Industrial hemp, grown for fiber or grain, is an emerging crop that has shown promise as a rotation alternative, although not much is known about its effects on soil health, agroecosystem functioning, and microbial communities. To better characterize hemp’s role within American agriculture, …

The Absence Of Cxcl10 Activity Does Not Affect The Capability Of Cd8+ T Cells To Migrate And Eliminate The Tissue Cysts Of Toxoplasma Gondii From The Brains Of Chronically Infected Mice, Rajesh Mani, Yasuhiro Suzuki

Markey Cancer Center Faculty Publications

Toxoplasma gondii forms tissue cysts in neurons and astrocytes in the brain to establish chronic infection, and astrocytes express the CXCL10 chemokine in chronically infected mice. Since chemokines mediate the migration of T cells to attack their targets, and since CXCL10 plays key roles in T cell-mediated control of the proliferation of tachyzoites (the acute stage form) of T. gondii during the acute stage of infection, we examined whether CXCL10 is involved in recruiting anti-cyst CD8+ cytotoxic T cells to eliminate the cysts in their brains. We employed adoptive transfer of CD8+ immune T cells to infected, T cell-deficient SCID …

Interferons In Viral Infections, Pracheta Sengupta, Saurabh Chattopadhyay

Markey Cancer Center Faculty Publications

No abstract provided.

Borrelia Burgdorferi Plza Is A Cyclic-Di-Gmp Dependent Dna And Rna Binding Protein, Nerina Jusufovic, Andrew Krusenstjerna, Christina R. Savage, Timothy C. Saylor, Catherine A. Brissette, Wolfram Zückert, Paula J. Schlax, Md A. Motaleb, Brian Stevenson

Entomology Faculty Publications

The PilZ domain-containing protein, PlzA, is the only known cyclic di- GMP binding protein encoded by all Lyme disease spirochetes. PlzA has been implicated in the regulation of many borrelial processes, but the effector mechanism of PlzA was not previously known. Here, we report that PlzA can bind DNA and RNA and that nucleic acid binding requires c-di-GMP, with the affinity of PlzA for nucleic acids increasing as concentrations of c-di-GMP were increased. A mutant PlzA that is incapable of bind- ing c-di-GMP did not bind to any tested nucleic acids. We also determined that PlzA interacts predominantly with the …

Staphylococcus Aureus Oleate Hydratase Produces Ligands That Activate Host Ppara, Christopher D. Radka, Matthew W. Frank, Tyler S. Simmons, Cydney N. Johnson, Jason W. Rosch, Charles O. Rock

Markey Cancer Center Faculty Publications

Commensal gut bacteria use oleate hydratase to release a spectrum of hydroxylated fatty acids using host-derived unsaturated fatty acids. These compounds are thought to attenuate the immune response, but the underlying signaling mechanism(s) remain to be established. The pathogen Staphylococcus aureus also expresses an oleate hydratase and 10- hydroxyoctadecanoic acid (h18:0) is the most abundant oleate hydratase metabolite found at Staphylococcal skin infection sites. Here, we show h18:0 stimulates the transcription of a set of lipid metabolism genes associated with the activation of peroxisome proliferator activated receptor (PPAR) in the RAW 264.7 macrophage cell line and mouse primary bone marrow-derived …

Hiv-1 Mrna Knockdown With Crispr/Cas9 Enhances Neurocognitive Function, Kristen A. Mclaurin, Hailong Li, Kamel Khalili, Charles F. Mactutus, Rosemarie M. Booze

Neurology Faculty Publications

Mixed glia are infiltrated with HIV-1 virus early in the course of infection leading to the development of a persistent viral reservoir in the central nervous system. Modification of the HIV-1 genome using gene editing techniques, including CRISPR/Cas9, has shown great promise towards eliminating HIV-1 viral reservoirs; whether these techniques are capable of removing HIV-1 viral proteins from mixed glia, however, has not been systematically evaluated. Herein, the efficacy of adeno-associated virus 9 (AAV9)-CRISPR/Cas9 gene editing for eliminating HIV-1 messenger RNA (mRNA) from cortical mixed glia was evaluated in vitro and in vivo. In vitro, a within-subjects experimental design was …

Revolutionizing Our Understanding Of Specific Platelet-Pathogen Interactions, Hammodah Rawhi Hammodah Alfar

Theses and Dissertations--Molecular and Cellular Biochemistry

Aside from their classical role in maintaining hemostasis, platelets are considered first-line vascular guardians that influence both the innate and adaptive immune systems. This is mediated by either direct interactions with immune cells or through the release of pre-stored cytokines and chemokines upon interacting with pathogens such as viruses. While this establishes platelets as potential players in the response to pathogens, it remains unclear what platelets can do with pathogens and how important that is to immune responses, especially against viruses. Most systemic viremias, such as HIV-1, present with mild thrombocytopenia, which is mediated through several mechanisms such as a …

Contributions Of The Replication Initiator Protein Dnaa To Physiology And Virulence Of The Lyme Disease Spirochete, Andrew Krusenstjerna

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Borrelia burgdorferi, the etiological agent of Lyme disease, is the most prevalent vector-borne disease in the United States. The spirochetal population is naturally maintained by consistently cycling between Ixodid ticks and small vertebrates. To survive within these diverse niches, B. burgdorferi has evolved a unique physiology and regulatory network to sense and respond to environmental fluxes. Replication is a hallmark of the Lyme spirochete’s enzootic life cycle, specifically at the nymphal tick-to-vertebrate interface. The mechanisms and regulatory schema for the basic cellular processes in B. burgdorferi, or indeed any member of the phylum spirochaetota, are largely unknown. The central hypothesis …

Role Of Autophagy-Related Genes In Lipid Transport For Efficient Replication Of Tombusviruses, Yuanrong Kang

Theses and Dissertations--Plant Pathology

Tombusviruses are positive-strand RNA viruses, which utilize numerous co-opted host factors and massive de-novo synthesized membrane resources to modify host membranes and form large viral replication organelles (VROs). Among plenty of host cellular processes, autophagy emerges as a potential membrane resource for VROs formation due to its ability to de-novo generate the double membrane structures, known as autophagosomes. Besides, as an important host defense pathway, autophagy is also a target for tombusviruses to prevent its antiviral activities. In this study, I identify the role of key autophagy related genes, Atg11, Atg8, and Atg2, which are involved in autophagosome formation, and …

Inflammation And Tumor Progression: The Differential Impact Of Saa In Breast Cancer Models, Daniel Wilhelm Olivier, Carla Eksteen, Manisha Du Plessis, Louis De Jager, Lize Engelbrecht, Nathaniel Wade Mcgregor, Preetha Shridas, Frederick C. De Beer, Willem J. S. De Villiers, Etheresia Pretorius, Anna-Mart Engelbrecht

Saha Cardiovascular Research Center Faculty Publications

Background: Previous research has shown that the Serum Amyloid A (SAA) protein family is intricately involved in inflammatory signaling and various disease pathologies. We have previously demonstrated that SAA is associated with increased colitis disease severity and the promotion of tumorigenesis. However, the specific role of SAA proteins in breast cancer pathology remains unclear. Therefore, we investigated the role of systemic SAA1 and SAA2 (SAA1/2) in a triple-negative breast cancer mouse model.

Methods: Syngeneic breast tumors were established in wild-type mice, and mice lacking the SAA1/2 (SAADKO). Subsequently, tumor volume was monitored, species survival determined, the inflammatory profiles of mice …

Co-Divergence Of Lemur Hosts And Gut Microbiomes Across Multiple Evolutionary Scales, Mariah E. Donohue

Theses and Dissertations--Biology

This dissertation bridges micro- and macroevolutionary approaches to understand the co-diversification of animal hosts and their gut microbiomes at different evolutionary timescales. I examined these dynamics using wild lemurs, a diverse Primate clade endemic to the island of Madagascar.

First, I tested the relative effects of host phylogenetic relationships, diet, and habitat in shaping the gut microbiome through deep evolutionary time and across distinct microbial kingdoms. I designed a natural experiment sampling feces from rainforest and dry forest lemur communities with similar phylogenetic assemblages and considerable variation in dietary strategy. Then, I amplified and sequenced two metabarcoding genes, the V4 …

Interactions Between Multiple Stressors, Nanomaterials And A Pathogen, In Caenorhabditis Elegans, Jarad Cochran

Theses and Dissertations--Plant and Soil Sciences

Metal and metal oxide nanoparticles (NP), which have received interest for use in agriculture, show in vitro and in vivo toxicity at relatively low concentrations. Silver nanoparticles (Ag NP) and zinc oxide nanoparticles (ZnO NP) cause adverse effects in model soil organisms under environmentally relevant conditions. In most toxicity assessments of nanomaterials, model organisms are exposed to a single stressor. Though single stressor experiments are essential to understanding the fate and effects of released NP, in nature, organisms are affected by multiple stressors, including pathogens, which might exacerbate or mitigate negative effects of NP exposure. There is limited research on …

Ecohiv-Infected Mice Show No Signs Of Platelet Activation, Hammodah Rawhi Hammodah Alfar, Dominic Ngima Nthenge-Ngumbau, Kathryn E. Saatman, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Platelets express several surface receptors that could interact with different viruses. To understand the mechanisms of HIV-1′s interaction with platelets, we chose the EcoHIV model. While EcoHIV is an established model for neuroAIDS, its effects on platelets are ill-defined. Our results indicate that EcoHIV behaves differently from HIV-1 and is cleared from circulation after 48 h post- infection. The EcoHIV course of infection resembles an HIV-1 infection under the effects of combined antiretroviral therapy (cART) since infected mice stayed immunocompetent and the virus was readily detected in the spleen. EcoHIV-infected mice failed to become thrombocytopenic and showed no signs of …

Immunization With The Amino-Terminus Region Of Dense Granule Protein 6 (Gra6) Of Toxoplasma Gondii Activates Cd8+ Cytotoxic T Cells Capable Of Removing Tissue Cysts Of The Parasite Through Antigen Presentation By Human Hla-A2.1, Rajesh Mani, Corinne Mercier, Marie-France Delauw, Yasuhiro Suzuki

Markey Cancer Center Faculty Publications

CD8þ T cells from HLA-A2.1-transgenic mice, but not wild-type mice, immunized with the amino- terminus region (aa 41e152) of dense granule protein 6 (GRA6Nt) of Toxoplasma gondii secreted large amounts of perforin and granzyme B in response to GRA6Nt through antigen presentation by HLA-A2.1 in vitro. When those CD8þ T cells were transferred into chronically infected HLA-A2.1-expressing NSG mice deficient in T cells, cerebral cyst burden of the recipients of HLA-A2.1-transgenic T cells, but not of WT T cells, became significantly less than that of control mice with no cell transfer. Furthermore, the significant reduction of the cyst burden by …

Inflammasome Activation And Pyroptosis Mediate Coagulopathy And Inflammation In Salmonella Systemic Infection, Ankit Pandeya, Yan Zhang, Jian Cui, Ling Yang, Jeffery Li, Guoying Zhang, Congqing Wu, Zhenyu Li, Yinan Wei

Saha Cardiovascular Research Center Faculty Publications

Inflammasome activation is a critical defense mechanism against bacterial infection. Previous studies suggest that inflammasome activation protects against Salmonella oral infection. Here we find inflammasome activation plays a critical role in the pathogenesis of Salmonella systemic infection. We show that in a systemic infection model by i.p. injection of Salmonella, deficiency of caspase-1 or gasdermin-D prolonged survival time, reduced plasma concentrations of the proinflammatory cytokines IL-1β, IL-6 and TNFα. These deficiencies also protected against coagulopathy during Salmonella infection as evidenced by diminished prolongation of prothrombin time and increase in plasma thrombin-antithrombin complex concentrations in the caspase-1 or gasdermin-D deficient mice. …

Protocol For Optimizing Production And Quality Control Of Infective Ecohiv Virions, Hammodah Rawhi Hammodah Alfar, Daphne N. Pariser, Harry Chanzu, Smita Joshi, Daniёlle M. Coenen, Joshua Lykins, Kanakanagavalli Shravani Prakhya, Mary Jane Potash, Wei Chao, Jennifer Kelschenbach, David J. Volsky, Kelly Metcalf-Pate

Saha Cardiovascular Research Center Faculty Publications

EcoHIV is a model of HIV infection that recapitulates aspects of HIV-1 pathology in mice. However, there are limited published protocols to guide EcoHIV virion production. Here, we present a protocol for producing infective EcoHIV virions and essential quality controls. We describe steps for viral purification, titering, and multiple techniques to analyze infection efficacy. This protocol produces high infectivity in C57BL/6 mice which will aid investigators in generating preclinical data.

Interferon-Stimulated Gene Tdrd7 Interacts With Ampk And Inhibits Its Activation To Suppress Viral Replication And Pathogenesis, Sukanya Chakravarty, Gayatri Subramanian, Sonam Popli, Manoj Veleeparambil, Shumin Fan, Ritu Chakravarti, Saurabh Chattopadhyay

Markey Cancer Center Faculty Publications

Many viruses activate cellular autophagy in infected cells to facilitate their replication. Recently, we identified an interferon (IFN)-stimulated gene (ISG) Tudor domain containing 7 (TDRD7), which inhibits viral replication by blocking autophagy pathway. Here, we present a molecular mechanism for TDRD7 action and its relative contribution to protection against viral pathogenesis. TDRD7 inhibited the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK), a kinase required for initiating autophagy. Mechanistically, TDRD7 interacted directly with AMPK in the cytosolic compartment. Domain-mapping analyses revealed C-terminal Tudor domain of TDRD7 interacted with auto-inhibitory domain of AMPK. Deletion of Tudor domains abolished anti-AMPK and antiviral …

Nac1 Confines Virus‐Specific Memory Formation Of Cd4+ T Cells Through The Rock1‐Mediated Pathway, Liqing Wang, Hao-Yun Peng, Jugal Kishore Das, Anil Kumar, Yijie Ren, Darby J. Ballard, Xiaofang Xiong, Wen Yang, Xingcong Ren, Paul De Figueiredo, Jin-Ming Yang, Jianxun Song

Markey Cancer Center Faculty Publications

Nucleus accumbens‐associated protein 1 (NAC1), a transcriptional cofactor, has been found to play important roles in regulating regulatory T cells, CD8 + T cells, and antitumor immunity, but little is known about its effects on T‐cell memory. In this study, we found that NAC1 expression restricts memory formation of CD4 + T cells during viral infection. Analysis of CD4 + T cells from wild‐type (WT) and NAC1‐ deficient (−/−) mice showed that NAC1 is essential for T‐cell metabolism, including glycolysis and oxidative phosphorylation, and supports CD4 + T‐cell survival in vitro. We further demonstrated that a deficiency of NAC1 downregulates …

Impact Of The Dimethyl Sulfoxide Reductase Superfamily On The Evolution Of Biogeochemical Cycles, Michael Wells, Minjae Kim, Denise M. Akob, Partha Basu, John F. Stolz

UK CARES Faculty Publications

The dimethyl sulfoxide reductase (or MopB) family is a diverse assemblage of enzymes found throughout Bacteria and Archaea. Many of these enzymes are believed to have been present in the last universal common ancestor (LUCA) of all cellular lineages. However, gaps in knowledge remain about how MopB enzymes evolved and how this diversification of functions impacted global biogeochemical cycles through geologic time. In this study, we perform maximum likelihood phylogenetic analyses on manually curated comparative genomic and metagenomic data sets containing over 47,000 distinct MopB homologs. We demonstrate that these enzymes constitute a catalytically and mechanistically diverse superfamily defined not …

Ferric Chloride-Induced Arterial Thrombosis And Sample Collection For 3d Electron Microscopy Analysis, Smita Joshi, Alexis N. Smith, Kanakanagavalli Shravani Prakhya, Hammodah Rawhi Hammodah Alfar, Joshua Lykins, Ming Zhang, Irina D. Pokrovskaya, Maria A. Aronova, Richard D. Leapman, Brian Storrie, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Cardiovascular diseases are a leading cause of mortality and morbidity worldwide. Aberrant thrombosis is a common feature of systemic conditions like diabetes and obesity, and chronic inflammatory diseases like atherosclerosis, cancer, and autoimmune diseases. Upon vascular injury, usually the coagulation system, platelets, and endothelium act in an orchestrated manner to prevent bleeding by forming a clot at the site of the injury. Abnormalities in this process lead to either excessive bleeding or uncontrolled thrombosis/insufficient antithrombotic activity, which translates into vessel occlusion and its sequelae. The FeCl3-induced carotid injury model is a valuable tool in probing how thrombosis initiates and progresses …

Ifn-Γ Production By Brain-Resident Cells Activates Cerebral Mrna Expression Of A Wide Spectrum Of Molecules Critical For Both Innate And T Cell-Mediated Protective Immunity To Control Reactivation Of Chronic Infection With Toxoplasma Gondii, Yasuhiro Suzuki, Jenny Lutshumba, Kuey Chu Chen, Mohamed H. Abdelaziz, Qila Sa, Eri Ochiai

Markey Cancer Center Faculty Publications

We previously demonstrated that brain-resident cells produce IFN-g in response to reactivation of cerebral infection with Toxoplasma gondii. To obtain an overall landscape view of the effects of IFN-g from brain-resident cells on the cerebral protective immunity, in the present study we employed NanoString nCounter assay and quantified mRNA levels for 734 genes in myeloid immunity in the brains of T and B cell-deficient, bone marrow chimeric mice with and without IFN-g production by brain-resident cells in response to reactivation of cerebral T. gondii infection. Our study revealed that IFN-g produced by brain-resident cells amplified mRNA expression for the molecules …

Recombinant Protein Vaccines Formulated With Enantio-Specific Cationic Lipid R-Dotap Induce Protective Cellular And Antibody-Mediated Immune Responses In Mice, Siva Gandhapudi, Hua Shi, Martin Ward, John Peyton Bush, Margarita G. Avdiushko, Karuna Sundarapandiyan, Lauren V. Wood, Mania Dorrani, Afsheen Fatima, Joe Dervan, Frank Bedu-Addo, Greg Conn, Ted M. Ross, Jerold Woodward

Markey Cancer Center Faculty Publications

Adjuvants are essential components of subunit vaccines added to enhance immune responses to antigens through immunomodulation. Very few adjuvants have been approved for human use by regulatory agencies due to safety concerns. Current subunit vaccine adjuvants approved for human use are very effective in promoting humoral immune responses but are less effective at promoting T-cell immunity. In this study, we evaluated a novel pure enantio-specific cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (R-DOTAP) as an immunomodulator for subunit vaccines capable of inducing both humoral- and cellular-mediated immunity. Using recombinant protein antigens derived from SARS-CoV2 spike or novel computationally optimized broadly reactive influenza antigen (COBRA) …