Microbiology | Open Access Articles | Digital Commons Network™

Monoclonal Antibodies Protect Aged Rhesus Macaques From Sars-Cov-2-Induced Immune Activation And Neuroinflammation, Anil Verma, Chase E. Hawes, Yashavanth Shaan Lakshmanappa, Jamin W. Roh, Brian A. Schmidt, Joseph Dutra, William Louie, Hongwei Liu, Zhong Min Ma, Jennifer K. Watanabe, Jodie L. Usachenko, Ramya Immareddy, Rebecca L. Sammak, Rachel Pollard, J. Rachel Reader, Katherine J. Olstad, Lark L. Coffey, Pamela A. Kozlowski, Dennis J. Hartigan-O'Connor, Michel Nussenzweig

School of Graduate Studies Faculty Publications

Anti-viral monoclonal antibody (mAb) treatments may provide immediate but short-term immunity from coronavirus disease 2019 (COVID-19) in high-risk populations, such as people with diabetes and the elderly; however, data on their efficacy in these populations are limited. We demonstrate that prophylactic mAb treatment blocks viral replication in both the upper and lower respiratory tracts in aged, type 2 diabetic rhesus macaques. mAb infusion dramatically curtails severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated stimulation of interferon-induced chemokines and T cell activation, significantly reducing development of interstitial pneumonia. Furthermore, mAb infusion significantly dampens the greater than 3-fold increase in SARS-CoV-2-induced effector CD4 …

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Human Genital Antibody-Mediated Inhibition Of Chlamydia Trachomatis Infection And Evidence For Ompa Genotype-Specific Neutralization, Caleb M. Ardizzone, Hannah L. Albritton, Rebecca A. Lillis, Caitlyn E.L. Bagnetto, Li Shen, Lisa A. Cavacini, Pamela A. Kozlowski, Alison J. Quayle

School of Graduate Studies Faculty Publications

The endocervix, the primary site of Chlamydia trachomatis (Ct) infection in women, has a unique repertoire of locally synthesized IgG and secretory IgA (SIgA) with contributions from serum IgG. Here, we assessed the ability of genital and serum-derived IgG and IgA from women with a recent positive Ct test to neutralize Ct elementary bodies (EBs) and inhibit inclusion formation in vitro in human endocervical epithelial cells. We also determined if neutralization was influenced by the major outer membrane protein (MOMP) of the infecting strain, as indicated by ompA gene sequencing and genotyping. At equivalent low concentrations of Ct EB (D/UW-3/Cx …

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Structural Polymorphism Of Chitin And Chitosan In Fungal Cell Walls From Solid-State Nmr And Principal Component Analysis, Liyanage D. Fernando, Malitha C. Dickwella Widanage, Jackson Penfield, Andrew S. Lipton, Nancy Washton, Jean Paul Latgé, Ping Wang, Liqun Zhang, Tuo Wang

School of Graduate Studies Faculty Publications

Chitin is a major carbohydrate component of the fungal cell wall and a promising target for novel antifungal agents. However, it is technically challenging to characterize the structure of this polymer in native cell walls. Here, we recorded and compared 13C chemical shifts of chitin using isotopically enriched cells of six Aspergillus, Rhizopus, and Candida strains, with data interpretation assisted by principal component analysis (PCA) and linear discriminant analysis (LDA) methods. The structure of chitin is found to be intrinsically heterogeneous, with peak multiplicity detected in each sample and distinct fingerprints observed across fungal species. Fungal chitin exhibits partial similarity …

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Pulmonary Immune Cell Trafficking Promotes Host Defense Against Alcohol-Associated Klebsiella Pneumonia, Derrick R. Samuelson, Min Gu, Judd E. Shellito, Patricia E. Molina, Christopher M. Taylor, Meng Luo, David A. Welsh

School of Graduate Studies Faculty Publications

The intestinal microbiota generates many different metabolites which are critical for the regulation of host signaling pathways. In fact, a wide-range of diseases are associated with increased levels of local or systemic microbe-derived metabolites. In contrast, certain bacterial metabolites, such as tryptophan metabolites, are known to contribute to both local and systemic homeostasis. Chronic alcohol consumption is accompanied by alterations to intestinal microbial communities, and their functional capacities. However, little is known about the role of alcohol-associated dysbiosis on host defense against bacterial pneumonia. Our previous work using fecal transplantation demonstrated that alcohol-associated intestinal dysbiosis, independent of ethanol consumption, increased …

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Invaplex Functions As An Intranasal Adjuvant For Subunit And Dna Vaccines Co-Delivered In The Nasal Cavity Of Nonhuman Primates, Jeremy V. Camp, Robert L. Wilson, Morgan Singletary, James L. Blanchard, Anna Aldovini, Robert W. Kaminski, Edwin V. Oaks, Pamela A. Kozlowski

School of Graduate Studies Faculty Publications

Development of intranasal vaccines for HIV-1 and other mucosal pathogens has been hampered by the lack of adjuvants that can be given safely to humans. We have found that an intranasal Shigella vaccine (Invaplex) which is well tolerated in humans can also function as an adjuvant for intranasal protein and DNA vaccines in mice. To determine whether Invaplex could potentially adjuvant similar vaccines in humans, we simultaneously administered a simian immunodeficiency virus (SIV) envelope (Env) protein and DNA encoding simian-human immunodeficiency virus (SHIV) with or without Invaplex in the nasal cavity of female rhesus macaques. Animals were intranasally boosted with …

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A Yeast Expressed Rbd-Based Sars-Cov-2 Vaccine Formulated With 3m-052-Alum Adjuvant Promotes Protective Efficacy In Non-Human Primates, Maria Pino, Talha Abid, Susan Pereira Ribeiro, Venkata Viswanadh Edara, Katharine Floyd, Justin C. Smith, Muhammad Bilal Latif, Gabriela Pacheco-Sanchez, Debashis Dutta, Shelly Wang, Sanjeev Gumber, Shannon Kirejczyk, Joyce Cohen, Rachelle L. Stammen, Sherrie M. Jean, Jennifer S. Wood, Fawn Connor-Stroud, Jeroen Pollet, Wen Hsiang Chen, Junfei Wei, Bin Zhan, Jungsoon Lee, Zhuyun Liu, Ulrich Strych, Neeta Shenvi, Kirk Easley, Daniela Weiskopf, Alesandro Sette

School of Graduate Studies Faculty Publications

Ongoing SARS-CoV-2 vaccine development is focused on identifying stable, cost-effective, and accessible candidates for global use, specifically in low and middle-income countries. Here, we report the efficacy of a rapidly scalable, novel yeast expressed SARS-CoV-2 specific receptor-binding domain (RBD) based vaccine in rhesus macaques. We formulated the RBD immunogen in alum, a licensed and an emerging alum adsorbed TLR-7/8 targeted, 3M-052-alum adjuvants. The RBD+3M-052-alum adjuvanted vaccine promoted better RBD binding and effector antibodies, higher CoV-2 neutralizing antibodies, improved Th1 biased CD4+T cell reactions, and increased CD8+ T cell responses when compared to the alum-alone adjuvanted vaccine. RBD+3M-052-alum induced a significant …

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Bispecific Anti-Hiv Immunoadhesins That Bind Gp120 And Gp41 Have Broad And Potent Hiv-Neutralizing Activity, Seth H. Pincus, Ryan B. Craig, Lauren Weachter, Celia C. Labranche, Rafiq Nabi, Connie Watt, Mark Raymond, Tami Peters, Kejing Song, Grace A. Maresh, David C. Montefiori, Pamela A. Kozlowski

School of Graduate Studies Faculty Publications

We have constructed bispecific immunoglobulin-like immunoadhesins that bind to both the HIV-envelope glycoproteins: gp120 and gp41. These immunoadhesins have N terminal domains of human CD4 engrafted onto the N-terminus of the heavy chain of human anti-gp41 mAb 7B2. Binding of these constructs to recombinant Env and their antiviral activities were compared to that of the parental mAbs and CD4, as well as to control mAbs. The CD4/7B2 constructs bind to both gp41 and gp140, as well as to native Env expressed on the surface of infected cells. These constructs deliver cytotoxic immunoconjugates to HIV-infected cells, but not as well as …

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Oral Vaccination Approaches For Anti-Shiv Immunity, Erandi Velarde De La Cruz, Lingyun Wang, Deepanwita Bose, Sailaja Gangadhara, Robert L. Wilson, Rama R. Amara, Pamela A. Kozlowski, Anna Aldovini

School of Graduate Studies Faculty Publications

We modified a Sabin Oral Poliovirus Vaccine (OPV) vector to permit secretion of the antigens of interest with the goal of improving anti-HIV Env humoral responses in a SHIV mucosal immunization composed of DNA and recombinant OPVs. We evaluated stimulation of systemic and mucosal cell-mediated and humoral immunity in Rhesus macaques by two regimens, both involving a prime with a SHIVBG505 DNA construct producing non-infectious particles formulated in lipid nanoparticles, administered in the oral cavity, and two different viral vector boostings, administered in the oral cavity and intestinally. Group 1 was boosted with rMVA-SHIVBG505, expressing SIV Gag/Pol and HIVBG505 Env. …

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Candida Cell‐Surface‐Specific Monoclonal Antibodies Protect Mice Against Candida Auris Invasive Infection, Jonothan Rosario‐Colon, Karen Eberle, Abby Adams, Evan Courville, Hong Xin

School of Graduate Studies Faculty Publications

Candida auris is a multidrug‐resistant fungal pathogen that can cause disseminated bloodstream infections with up to 60% mortality in susceptible populations. Of the three major classes of antifungal drugs, most C. auris isolates show high resistance to azoles and polyenes, with some clinical isolates showing resistance to all three drug classes. We reported in this study a novel approach to treating C. auris disseminated infections through passive transfer of monoclonal antibodies (mAbs) targeting cell surface antigens with high homology in medically important Candida spe-cies. Using an established A/J mouse model of disseminated infection that mimics human candidi-asis, we showed that …

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The Rice Blast Fungus Morgs1 Functioning In Camp Signaling And Pathogenicity Is Regulated By Casein Kinase Mock2 Phosphorylation And Modulated By Membrane Protein Moemc2, Rui Yu, Xuetong Shen, Muxing Liu, Xinyu Liu, Ziyi Yin, Xiao Li, Wanzhen Feng, Jiexiong Hu, Haifeng Zhang, Xiaobo Zheng, Ping Wang, Zhengguang Zhang

School of Graduate Studies Faculty Publications

GTP-binding protein (G-protein) and regulator of G-protein signaling (RGS) mediated signal transduction are critical in the growth and virulence of the rice blast pathogen Magnaporthe oryzae. We have previously reported that there are eight RGS and RGS-like proteins named MoRgs1 to MoRgs8 playing distinct and shared regulatory functions in M. oryzae and that MoRgs1 has a more prominent role compared to others in the fungus. To further explore the unique regulatory mechanism of MoRgs1, we screened a M. oryzae cDNA library for genes encoding MoRgs1-interacting proteins and identified MoCkb2, one of the two regulatory subunits of the casein kinase (CK) …

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Sars-Cov-2 Vaccines Elicit Durable Immune Responses In Infant Rhesus Macaques, Carolina Garrido, Alan D. Curtis, Maria Dennis, Sachi H. Pathak, Hongmei Gao, David Montefiori, Mark Tomai, Christopher B. Fox, Pamela A. Kozlowski, Trevor Scobey, Jennifer E. Munt, Michael L. Mallory, Pooja T. Saha, Michael G. Hudgens, Lisa C. Lindesmith, Ralph S. Baric, Olubukola M. Abiona, Barney S. Graham, Kizzmekia S. Corbett, Darin Edwards

School of Graduate Studies Faculty Publications

The inclusion of infants in the SARS-CoV-2 vaccine rollout is important to prevent severe complications of pediatric SARS-CoV-2 infections and to limit transmission and could possibly be implemented via the global pediatric vaccine schedule. However, age-dependent differences in immune function require careful evaluation of novel vaccines in the pediatric population. Toward this goal, we assessed the safety and immunogenicity of two SARSCoV- 2 vaccines. Two groups of eight infant rhesus macaques (RMs) were immunized intramuscularly at weeks 0 and 4 with stabilized prefusion SARS-CoV-2 S-2P spike (S) protein encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or the purified S …

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Differences In The Genital Microbiota In Women Who Naturally Clear Chlamydia Trachomatis Infection Compared To Women Who Do Not Clear; A Pilot Study, Patricia Dehon Mott, Christopher M. Taylor, Rebecca A. Lillis, Caleb M. Ardizzone, Hannah L. Albritton, Meng Luo, Kaitlyn G. Calabresi, David H. Martin, Leann Myers, Alison J. Quayle

School of Graduate Studies Faculty Publications

In vitro studies indicate IFNγ is central to Chlamydia trachomatis (Ct) eradication, but its function may be compromised by anaerobes typically associated with bacterial vaginosis (BV), a frequent co-morbidity in women with Ct. Here we investigated the associations between natural clearance of cervical Ct infection, the vaginal microbiome, and the requirements for IFNγ by evaluating the vaginal microbial and cytokine composition of Ct treatment visit samples from women who cleared Ct infection in the interim between their Ct screening and Ct treatment visit. The pilot cohort was young, predominantly African American, and characterized by a high rate of BV that …

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School of Graduate Studies Faculty Publications

Human Genital Antibody-Mediated Inhibition Of Chlamydia Trachomatis Infection And Evidence For Ompa Genotype-Specific Neutralization, Caleb M. Ardizzone, Hannah L. Albritton, Rebecca A. Lillis, Caitlyn E.L. Bagnetto, Li Shen, Lisa A. Cavacini, Pamela A. Kozlowski, Alison J. Quayle

School of Graduate Studies Faculty Publications

Structural Polymorphism Of Chitin And Chitosan In Fungal Cell Walls From Solid-State Nmr And Principal Component Analysis, Liyanage D. Fernando, Malitha C. Dickwella Widanage, Jackson Penfield, Andrew S. Lipton, Nancy Washton, Jean Paul Latgé, Ping Wang, Liqun Zhang, Tuo Wang

School of Graduate Studies Faculty Publications

Pulmonary Immune Cell Trafficking Promotes Host Defense Against Alcohol-Associated Klebsiella Pneumonia, Derrick R. Samuelson, Min Gu, Judd E. Shellito, Patricia E. Molina, Christopher M. Taylor, Meng Luo, David A. Welsh

School of Graduate Studies Faculty Publications

Invaplex Functions As An Intranasal Adjuvant For Subunit And Dna Vaccines Co-Delivered In The Nasal Cavity Of Nonhuman Primates, Jeremy V. Camp, Robert L. Wilson, Morgan Singletary, James L. Blanchard, Anna Aldovini, Robert W. Kaminski, Edwin V. Oaks, Pamela A. Kozlowski

School of Graduate Studies Faculty Publications

School of Graduate Studies Faculty Publications

Bispecific Anti-Hiv Immunoadhesins That Bind Gp120 And Gp41 Have Broad And Potent Hiv-Neutralizing Activity, Seth H. Pincus, Ryan B. Craig, Lauren Weachter, Celia C. Labranche, Rafiq Nabi, Connie Watt, Mark Raymond, Tami Peters, Kejing Song, Grace A. Maresh, David C. Montefiori, Pamela A. Kozlowski

School of Graduate Studies Faculty Publications

Oral Vaccination Approaches For Anti-Shiv Immunity, Erandi Velarde De La Cruz, Lingyun Wang, Deepanwita Bose, Sailaja Gangadhara, Robert L. Wilson, Rama R. Amara, Pamela A. Kozlowski, Anna Aldovini

School of Graduate Studies Faculty Publications

Candida Cell‐Surface‐Specific Monoclonal Antibodies Protect Mice Against Candida Auris Invasive Infection, Jonothan Rosario‐Colon, Karen Eberle, Abby Adams, Evan Courville, Hong Xin

School of Graduate Studies Faculty Publications

School of Graduate Studies Faculty Publications

School of Graduate Studies Faculty Publications

School of Graduate Studies Faculty Publications