Medical Sciences Commons^™

Human Neutralizing Antibodies Target A Conserved Lateral Patch On H7n9 Hemagglutinin Head, Manxue Jia, Hanjun Zhao, Nicholas C Morano, Hong Lu, Yin-Ming Lui, Haijuan Du, Jordan E Becker, Kwok-Yung Yuen, David D Ho, Peter D Kwong, Lawrence Shapiro, Kelvin Kai-Wang To, Xueling Wu

Journal Articles

Avian influenza A virus H7N9 causes severe human infections with >30% fatality. Currently, there is no H7N9-specific prevention or treatment for humans. Here, from a 2013 H7N9 convalescent case in Hong Kong, we isolate four hemagglutinin (HA)-reactive monoclonal antibodies (mAbs), with three directed to the globular head domain (HA1) and one to the stalk domain (HA2). Two clonally related HA1-directed mAbs, H7.HK1 and H7.HK2, potently neutralize H7N9 and protect female mice from lethal H7N9/AH1 challenge. Cryo-EM structures reveal that H7.HK1 and H7.HK2 bind to a β14-centered surface and disrupt the 220-loop that makes hydrophobic contacts with sialic acid on an …

Xtx101, A Tumor-Activated, Fc-Enhanced Anti-Ctla-4 Monoclonal Antibody, Demonstrates Tumor-Growth Inhibition And Tumor-Selective Pharmacodynamics In Mouse Models Of Cancer, Kurt A. Jenkins, Miso Park, Magali Pederzoli-Ribeil, Ugur Eskiocak, Parker Johnson, Wilson Guzman, Megan Mclaughlin, Deborah Moore-Lai, Caitlin O'Toole, Zhen Liu, Benjamin Nicholson, Veronica Flesch, Huawei Qiu, Tim Clackson, Ronan C. O'Hagan, Ulrich Rodeck, Margaret Karow, Jennifer O'Neil, John C. Williams

Department of Dermatology and Cutaneous Biology Faculty Papers

INTRODUCTION: The clinical benefit of the anti-CTLA-4 monoclonal antibody (mAb) ipilimumab has been well established but limited by immune-related adverse events, especially when ipilimumab is used in combination with anti-PD-(L)1 mAb therapy. To overcome these limitations, we have developed XTX101, a tumor-activated, Fc-enhanced anti-CTLA-4 mAb.

METHODS: XTX101 consists of an anti-human CTLA-4 mAb covalently linked to masking peptides that block the complementarity-determining regions, thereby minimizing the mAb binding to CTLA-4. The masking peptides are designed to be released by proteases that are typically dysregulated within the tumor microenvironment (TME), resulting in activation of XTX101 intratumorally. Mutations within the Fc region …

How Irish Medical Scientists Can Assist In The Improved Diagnosis Of Disease - Infectious Mononucleosis (Im) A Case In Point, Patrick Naughton

ORBioM (Open Research BioSciences Meeting)

The Epstein-Barr Virus (EBV) or human herpesvirus 4 (HHV-4) is the sole etiologic agent of the acute illness in humans described either as infectious mononucleosis (IM), or glandular fever. IM is a self-limiting disease with various but transient symptoms which include fever, fatigue, malaise, sore throat, swollen lymph glands (particularly of the neck), swollen liver and spleen. Diagnosis relies on clear, timely and informative laboratory test results. Patients with primary IM infection often present on investigation with a well-documented population of atypical/plasmacytoid lymphocytes. The qualitative detection of heterophile antibodies (HAs) is also a useful aid in the diagnosis of primary …

Simtutor Module: Antibodies, Heather Gilbert

Teaching, Learning, and Scholarship (TLAS) Academy Projects

Antibody simulation module developed for use in MLS 226: Introduction to Clinical Immunology and Molecular Diagnostics. The module was designed to reinforce lecture material and was developed utilizing SimTutor software.

Learning outcomes:

1. Define antibody.
2. Differentiate between innate and adaptive immunity.
3. Differentiate between cellular and humoral immunity.
4. Describe the four pathways of antibody acquisition.
5. Identify the three functions of an antibody.
6. Identify and describe the structure of an antibody including the following components and regions: light chain, heavy chain, constant region, variable region, Fc Fragment, Fab Fragment, and hinge region.
7. List the antibody classes and their key features.
8. Differentiate between the …

Igg3 Subclass Antibodies Recognize Antigenically Drifted Influenza Viruses And Sars-Cov-2 Variants Through Efficient Bivalent Binding, Marcus J. Bolton, Jefferson J.S. Santos, Claudia P. Arevalo, Trevor Griesman, Megan Watson, Shuk Hang Li, Paul Bates, Holly Ramage, Patrick C. Wilson, Scott E. Hensley

Department of Microbiology and Immunology Faculty Papers

The constant domains of antibodies are important for effector functions, but less is known about how they can affect binding and neutralization of viruses. Here, we evaluated a panel of human influenza virus monoclonal antibodies (mAbs) expressed as IgG1, IgG2, or IgG3. We found that many influenza virus-specific mAbs have altered binding and neutralization capacity depending on the IgG subclass encoded and that these differences result from unique bivalency capacities of the subclasses. Importantly, subclass differences in antibody binding and neutralization were greatest when the affinity for the target antigen was reduced through antigenic mismatch. We found that antibodies expressed …

A Computationally Designed Ace2 Decoy Has Broad Efficacy Against Sars-Cov-2 Omicron Variants And Related Viruses In Vitro And In Vivo, Brandon Havranek, Graeme Walker Lindsey, Yusuke Higuchi, Yumi Itoh, Tatsuya Suzuki, Toru Okamoto, Atsushi Hoshino, Erik Procko, Shahidul M. Islam

SKMC Student Presentations and Publications

SARS-CoV-2, especially B.1.1.529/omicron and its sublineages, continues to mutate to evade monoclonal antibodies and antibodies elicited by vaccination. Affinity-enhanced soluble ACE2 (sACE2) is an alternative strategy that works by binding the SARS-CoV-2 S protein, acting as a 'decoy' to block the interaction between the S and human ACE2. Using a computational design strategy, we designed an affinity-enhanced ACE2 decoy, FLIF, that exhibited tight binding to SARS-CoV-2 delta and omicron variants. Our computationally calculated absolute binding free energies (ABFE) between sACE2:SARS-CoV-2 S proteins and their variants showed excellent agreement to binding experiments. FLIF displayed robust therapeutic utility against a broad range …

Antibodies For Β2-Microglobulin And The Heavy Chains Of Hla-E, Hla-F, And Hla-G Reflect The Hla-Variants On Activated Immune Cells And Phases Of Disease Progression In Rheumatoid Arthritis Patients Under Treatment, Mepur H. Ravindranath, Narendranath M. Ravindranath, Carly J. Amato-Menker, Fatiha El Hilali, Senthamil R. Selvan, Edward J Filippone, Luis Eduardo Morales-Buenrostro

Department of Medicine Faculty Papers

Rheumatoid arthritis (RA) is a progressive, inflammatory, autoimmune, symmetrical polyarticular arthritis. It is characterized by synovial infiltration and activation of several types of immune cells, culminating in their apoptosis and antibody generation against "altered" autoantigens. β2-microglobulin (β2m)-associated heavy chains (HCs) of HLA antigens, also known as closed conformers (Face-1), undergo "alteration" during activation of immune cells, resulting in β2m-free structural variants, including monomeric open conformers (Face-2) that are capable of dimerizing as either homodimers (Face-3) or as heterodimers (Face-4). β2m-free HCs uncover the cryptic epitopes that can elicit antibodies (Abs). We report here the levels of IgM and IgG Abs …

Design And Preclinical Evaluation Of A Universal Sars-Cov-2 Mrna Vaccine, Jane Qin, Ju Hyeong Jeon, Jiangsheng Xu, Laura Katherine Langston, Ramesh Marasini, Stephanie Mou, Brian Montoya, Carolina R Melo-Silva, Hyo Jin Jeon, Tianyi Zhu, Luis J. Sigal, Renhuan Xu, Huabin Zhu

Department of Microbiology and Immunology Faculty Papers

Because of the rapid mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an effective vaccine against SARS-CoV-2 variants is needed to prevent coronavirus disease 2019 (COVID-19). T cells, in addition to neutralizing antibodies, are an important component of naturally acquired protective immunity, and a number of studies have shown that T cells induced by natural infection or vaccination contribute significantly to protection against several viral infections including SARS-CoV-2. However, it has never been tested whether a T cell-inducing vaccine can provide significant protection against SARS-CoV-2 infection in the absence of preexisting antibodies. In this study, we designed and evaluated …

Screening Of Antigliadin And Antitissue Transglutaminase Antibodies In Patients With Chronic Plaque Psoriasis: A Case-Control Study, Burhan Engi̇n, Chinara Huseynova, Tümay Ak, Ali̇ Yağiz Ayla, Günay Can, Serdal Uğurlu

Turkish Journal of Medical Sciences

Background/aim: In this study, we aimed to investigate different types of celiac antibodies in psoriasis patients and to see if the presence of the antibodies was associated with other variables. Materials and methods: We included patients with plaque psoriasis who were followed up in our dermatology clinic between February 2019 and February 2021 and added a healthy control group for comparison. The antibodies studied were serum antitissue transglutaminase (tTG)-IgA, tTG-IgG, antigliadin antibody (AGA)-IgA, and AGA-IgG. The patients' records were used to note age, sex, the pattern of psoriasis involvement, psoriasis area and severity index (PASI), presence of hypertension, presence of …

A Longitudinal Seroepidemiology Study To Evaluate Antibody Response To Sars-Cov-2 Virus Infection And Vaccination In Children In Calgary, Canada From July 2020 To April 2022: Alberta Covid-19 Childhood Cohort (Ab3c) Study, Emily J Doucette, Joslyn Gray, Kevin Fonseca, Carmen Charlton, Jamil N Kanji, Graham Tipples, Susan Kuhn, Jessica Dunn, Payton Sayers, Nicola Symonds, Guosong Wu, Stephen B Freedman, James D Kellner

Journal Articles

BACKGROUND: Measurement of SARS-CoV-2 antibody seropositivity is important to accurately understand exposure to infection and/or vaccination in specific populations. This study aimed to estimate the serologic response to SARS-CoV-2 virus infection and vaccination in children in Calgary, Alberta over a two-year period.

METHODS: Children with or without prior SARS-CoV-2 infections, were enrolled in Calgary, Canada in 2020. Venous blood was sampled 4 times from July 2020 to April 2022 for SARS-CoV-2 nucleocapsid and spike antibodies. Demographic and clinical information was obtained including SARS-CoV-2 testing results and vaccination records.

RESULTS: 1035 children were enrolled and 88.9% completed all 4 visits; median …

The Prevalence Of Sars-Cov-2 Antibodies Within The Community Of A Private Tertiary University In The Philippines: A Serial Cross Sectional Study, Lourdes S. Tanchanco, Jenica Clarisse Y. Sy, Angel Belle C. Dy, Myla D. Levantino, Arianna Maever L. Amit, John Wong, Kirsten Angeles, John Paul Vergara

Ateneo School of Medicine and Public Health Publications

The COVID-19 pandemic has caused a public health emergency in all sectors of society, including universities and other academic institutions. This study determined the seroprevalence of SARS-CoV-2 antibodies among administrators, faculty, staff, and students of a private tertiary academic institution in the Philippines over a 7 month period. It employed a serial cross-sectional method using qualitative and quantitative COVID-19 antibody test kits. A total of 1,318 participants were tested, showing 47.80% of the study population yielding IgG antibodies to SARS-CoV-2 virus. A general increase in seroprevalence was observed from June to December 2021, which coincided with the vaccine roll-out of …

How Irish Medical Scientists Can Assist In The Improved Diagnosis Of The Disease Infectious Mononucleosis, Patrick Naughton

ORBioM (Open Research BioSciences Meeting)

Background:

The eponymously named Epstein-Barr Virus (EBV) or human herpesvirus 4 (HHV-4) is the sole causative agent of the acute illness in humans described either as infectious mononucleosis (IM), or glandular fever. IM, when not clinically silent, can present in patients with at least two of the classic triad of symptoms of fever, pharyngitis, and lymphadenopathy. Challenges for the clinician arise when atypical cases present. Early, accurate and informed laboratory test results are vital for diagnosis, appropriate treatment, and patient management. A key challenge for the practitioner, particularly in cases where the illness can present atypically, is distinguishing bacterial tonsillitis …

A Single Dose Of The Deactivated Rabies-Virus Vectored Covid-19 Vaccine, Coravax, Is Highly Efficacious And Alleviates Lung Inflammation In The Hamster Model, Drishya Kurup, Christoph Wirblich, Leila Zabihi Diba, Rachael Lambert, Megan Watson, Noor Shaikh, Holly Ramage, Charalambos Solomides, Matthias J Schnell

Department of Microbiology and Immunology Faculty Papers

Without sufficient herd immunity through either vaccination or natural infection, the coronavirus disease 2019 pandemic is unlikely to be controlled. Waning immunity with the currently approved vaccines suggests the need to evaluate vaccines causing the induction of long-term responses. Here, we report the immunogenicity and efficacy of our adjuvanted single-dose Rabies-vectored SARS-CoV-2 S1 vaccine, CORAVAX, in hamsters. CORAVAX induces high SARS-CoV-2 S1-specific and virus-neutralizing antibodies (VNAs) that prevent weight loss, viral loads, disease, lung inflammation, and the cytokine storm in hamsters. We also observed high Rabies VNA titers. In summary, CORAVAX is a promising dual-antigen vaccine candidate for clinical evaluation …

Antigen Staining For Detection Of Muc13 And Muc16 Expression In Carcinoma Tissue, Jose A. Benitez

MEDI 9331 Scholarly Activities Clinical Years

MUC13 and MUC16 are epithelial expressed proteins implicated in various carcinomas. Overexpression of these biomarkers appear to play a role in tumor growth; this discovery has paved a road for multiple studies discussing the potential of targeting mucin proteins and optimize immunotherapy approaches against carcinomas. Our study serves to investigate the level of expression of MUC13 and MUC16 in cancerous and normal tissue and to discuss the implications our findings may have for the utilization of these biomarkers for cancer therapy.

Effect Of Tocilizumab On Intensive Care Patients With Covid-19 Pneumonia, A Retrospective Cohort Study, Mehtap Pehli̇vanlar Küçük, Ahmet Oğuzhan Küçük, Ayşegül Pehli̇vanlar, Emi̇ne Sevi̇l Ayaydin Mürtezaoğlu, Kadi̇r Çoban, Gamze Kiliç, Olcay Ayçi̇çek, Funda Öztuna, Yilmaz Bülbül, Tevfi̇k Özlü

Turkish Journal of Medical Sciences

Backround/aim: In this study, the efficacy of an IL-6 antagonist, Tocilizumab, administered in the early period was studied in intensive care patients with COVID-19 pneumonia followed by hypoxic and systemic inflammation not receiving mechanical ventilation support. Materials and methods: Patients with COVID-19 pneumonia who have signs of hypoxia and systemic inflammation and/or who have acute bilateral infiltrates on chest radiograph and who received tocilizumab treatment were compared with the patients who received standard medical therapy. Patients who were followed up with COVID-19 pneumonia and respiratory failure between March 2020 and March 2021 were retrospectively evaluated in the study. A 400 …

A Serological Analysis Of Sars-Cov-2 Infection In The Obstetric Population, Sophia Rose

CMC Senior Theses

In December 2019, the surfacing and spread of a novel coronavirus, SARS-CoV-2, resulted in the global COVID-19 pandemic. As a viral antigen, SARS-CoV-2 poses a particular threat to the obstetric population due to physiological and immunological changes that women face during pregnancy. While recent studies have found that SARS-CoV-2 may have better clinical outcomes as compared to other betacoronaviruses, adverse pregnancy events such as ICU admission, preeclampsia, and/or preterm birth have been associated with COVID-19. Progress has been made in better understanding the pathophysiology of SARS-CoV-2 in pregnancy, but there is still much to be known about the interaction …

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 species. Using an established A/J mouse model of disseminated infection that mimics human candidiasis, we showed that …

Inactivated Rabies Virus Vectored Sars-Cov-2 Vaccine Prevents Disease In A Syrian Hamster Model., Drishya Kurup, Delphine C Malherbe, Christoph Wirblich, Rachael Lambert, Adam J Ronk, Leila Zabihi Diba, Alexander Bukreyev, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent coronavirus that has caused a worldwide pandemic. Although human disease is often asymptomatic, some develop severe illnesses such as pneumonia, respiratory failure, and death. There is an urgent need for a vaccine to prevent its rapid spread as asymptomatic infections accounting for up to 40% of transmission events. Here we further evaluated an inactivated rabies vectored SARS-CoV-2 S1 vaccine CORAVAX in a Syrian hamster model. CORAVAX adjuvanted with MPLA-AddaVax, a TRL4 agonist, induced high levels of neutralizing antibodies and generated a strong Th1-biased immune response. Vaccinated hamsters were protected from …

The Current Landscape Of Antibody-Based Therapies In Solid Malignancies, Ashu Shah, Sanchita Rauth, Abhijit Aithal, Sukhwinder Kaur, Koelina Ganguly, Catherine Orzechowski, Grish C. Varshney, Maneesh Jain, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Over the past three decades, monoclonal antibodies (mAbs) have revolutionized the landscape of cancer therapy. Still, this benefit remains restricted to a small proportion of patients due to moderate response rates and resistance emergence. The field has started to embrace better mAb-based formats with advancements in molecular and protein engineering technologies. The development of a therapeutic mAb with long-lasting clinical impact demands a prodigious understanding of target antigen, effective mechanism of action, gene engineering technologies, complex interplay between tumor and host immune system, and biomarkers for prediction of clinical response. This review discusses the various approaches used by mAbs for …

Programmed Death Pathway Inhibition: Emerging Therapeutic Options For Treatment Of Advanced Or Refractory Cancers, Katherine Elsass, Morgan Homan, Jana Randolph, Brendan Rasor, David Kinder

Pharmacy and Wellness Review

The programmed death-1 (PD-1) pathway has a significant role in the promotion of immune tolerance. The PD-1 receptor ligands are normally expressed on various inactive immune cells. When cancer cells express these ligands, they are able to interact with active T and B lymphocytes to induce this tolerance. Nivolumab and pembrolizumab are two recently approved agents that act to disrupt this binding and facilitate an immune response against cancer cells. Numerous trials, including KEYNOTE-002 and CheckMate 063, have demonstrated the superior safety and efficacy of these drugs in patients with advanced or refractory cancers. Initially approved for the treatment of …

Pcsk9 Inhibitors: A Novel Class Of Pharmacotherapy For Hypercholesterolemia, Angela Chu, Austin Hilverding, Elizabeth Kramer, Brendan Rasor, Boyd Rorabaugh

Pharmacy and Wellness Review

The recent U.S. Food and Drug Administration (FDA) approval of two new drugs, alirocumab (Praluent®) and evolocumab (Repatha®) is a breakthrough in the treatment of familial hypercholesterolemia. These drugs are a part of a new class called the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors that act by increasing the number of low density lipoprotein receptors (LDL-R) recycled to hepatocyte membranes. The increased density of LDL-R facilitates greater clearance of low density lipoproteins from the blood. Numerous clinical trials have demonstrated the efficacy of these agents, particularly for patients in whom standard cholesterol-lowering therapy is insufficient. However, data on long-term …

Antibodies In The Diagnosis, Prognosis, And Prediction Of Psychotic Disorders., Thomas A Pollak, Jonathan P Rogers, Robert G Nagele, Mark Peakman, James M Stone, Anthony S David, Philip Mcguire

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Blood-based biomarker discovery for psychotic disorders has yet to impact upon routine clinical practice. In physical disorders antibodies have established roles as diagnostic, prognostic and predictive (theranostic) biomarkers, particularly in disorders thought to have a substantial autoimmune or infective aetiology. Two approaches to antibody biomarker identification are distinguished: a "top-down" approach, in which antibodies to specific antigens are sought based on the known function of the antigen and its putative role in the disorder, and emerging "bottom-up" or "omics" approaches that are agnostic as to the significance of any one antigen, using high-throughput arrays to identify distinctive components of the …

Kaposi’S Sarcoma-Associated Herpesvirus Seropositivity Is Associated With Type 2 Diabetes Mellitus: A Case–Control Study In Xinjiang, China, Meng Cui, Qiwen Fang, Jun Zheng, Zhanjun Shu, Yin Chen, Yage Fan, Juan Zhao, Charles Wood, Tiejun Zhang, Yan Zeng

Nebraska Center for Virology: Faculty Publications

Objective: To assess the potential relationship between Kaposi’s sarcoma-associated herpesvirus (KSHV) infection and type 2 diabetes mellitus (DM-2) in Xinjiang, China.

Methods: A case–control study of consecutively included DM-2 patients and normal controls was conducted among the Uygur and Han populations in Xinjiang Uygur Autonomous Region, China. Blood samples were collected and KSHV seroprevalence, antibody titers, and viral load were investigated. Logistic regression analysis and multiple linear regression analysis were applied to explore determinants of the main outcome measures.

Results: A total of 324 patients with DM-2 and 376 normal controls were included. The seroprevalence of KSHV was 49.1% (95% …

Immunization Elicits Antigen-Specific Antibody Sequestration In Dorsal Root Ganglia Sensory Neurons, M. Gunasekaran, P. K. Chatterjee, A. Shih, G. H. Imperato, G. Kumar, A. Lee, C. Bouton, B. Sherry, B. Diamond, T. R. Coleman, C. N. Metz, K. J. Tracey, S. S. Chavan, +9 Additional Authors

Journal Articles

No abstract provided.

Editorial: Neuro-Immune Interactions In Inflammation And Autoimmunity, N. Terrando, V. A. Pavlov

Journal Articles

No abstract provided.

April:Taci Axis Is Dispensable For The Immune Response To Rabies Vaccination., Shannon L. Haley, Evgeni P. Tzvetkov, Andrew G. Lytle, Kishore R. Alugupalli, Joseph R. Plummer, James P. Mcgettigan

Department of Microbiology and Immunology Faculty Papers

There is significant need to develop a single-dose rabies vaccine to replace the current multi-dose rabies vaccine regimen and eliminate the requirement for rabies immune globulin in post-exposure settings. To accomplish this goal, rabies virus (RABV)-based vaccines must rapidly activate B cells to secrete antibodies which neutralize pathogenic RABV before it enters the CNS. Increased understanding of how B cells effectively respond to RABV-based vaccines may improve efforts to simplify post-exposure prophylaxis (PEP) regimens. Several studies have successfully employed the TNF family cytokine a proliferation-inducing ligand (APRIL) as a vaccine adjuvant. APRIL binds to the receptors TACI and B cell …

Boosting Of Hiv Envelope Cd4 Binding Site Antibodies With Long Variable Heavy Third Complementarity Determining Region In The Randomized Double Blind Rv305 Hiv-1 Vaccine Trial, David Easterhoff, M. Anthony Moody, Daniela Fera, Hao Cheng, Margaret Ackerman

Dartmouth Scholarship

The canary pox vector and gp120 vaccine (ALVAC-HIV and AIDSVAX B/E gp120) in the RV144 HIV-1 vaccine trial conferred an estimated 31% vaccine efficacy. Although the vaccine Env AE.A244 gp120 is antigenic for the unmutated common ancestor of V1V2 broadly neutralizing antibody (bnAbs), no plasma bnAb activity was induced. The RV305 (NCT01435135) HIV-1 clinical trial was a placebo-controlled randomized double-blinded study that assessed the safety and efficacy of vaccine boosting on B cell repertoires. HIV-1- uninfected RV144 vaccine recipients were reimmunized 6–8 years later with AIDSVAX B/E gp120 alone, ALVAC-HIV alone, or a combination of ALVAC-HIV and AIDSVAX B/E gp120 …

Immunogenicity And Protective Efficacy Of The Dar-901 Booster Vaccine In A Murine Model Of Tuberculosis, Timothy Lahey, Dominick Laddy, Krystal Hill, Jacqueline Schaeffer

Dartmouth Scholarship

The development of a novel tuberculosis vaccine is a leading global health priority. SRL172, an inactivated, whole-cell mycobacterial vaccine, was safe, immunogenic and reduced the incidence of culture-confirmed tuberculosis in a phase III trial in HIV-infected and BCG immunized adults in Tanzania. Here we describe the immunogenicity and protective efficacy of DAR-901, a booster vaccine against tuberculosis manufactured from the same seed strain using a new scalable method.

Animal-Friendly Affinity Reagents: Replacing The Needless In The Haystack, A. C. Gray, S. S. Sidhu, P. C. Chandrasekera, C. F.M. Hendriksen, C. A.K. Borrebaeck

Biomedicine and Animal Models in Research Collection

The multibillion-dollar global antibody industry produces an indispensable resource but that is generated using millions of animals. Despite the irrefutable maturation and availability of animal-friendly affinity reagents (AFAs) employing na€ive B lymphocyte or synthetic recombinant technologies expressed by phage display, animal immunisation is still authorised for antibody production. Remarkably, replacement opportunities have been overlooked, despite the enormous potential reduction in animal use. Directive 2010/63/EU requires that animals are not used where alternatives exist. To ensure its implementation, we have engaged in discussions with the EU Reference Laboratory for alternatives to animal testing (EURL ECVAM) and the Directorate General for Environment …

An Ultrasensitive Electrogenerated Chemiluminescence-Based Immunoassay For Specific Detection Of Zika Virus, Amber M. Paul, Dhiraj Acharya, Pradip Bastola, Linda Le, Estenfani Fernandez, Michael S. Diamond, Wujian Miao, Fengwei Bai

Publications

Zika virus (ZIKV) is a globally emerging mosquito-transmitted flavivirus that can cause severe fetal abnormalities, including microcephaly. As such, highly sensitive, specific, and cost-effective diagnostic methods are urgently needed. Here, we report a novel electrogenerated chemiluminescence (ECL)-based immunoassay for ultrasensitive and specific detection of ZIKV in human biological fluids. We loaded polystyrene beads (PSB) with a large number of ECL labels and conjugated them with anti-ZIKV monoclonal antibodies to generate anti-ZIKV-PSBs. These anti-ZIKV-PSBs efficiently captured ZIKV in solution forming ZIKV-anti-ZIKV-PSB complexes, which were subjected to measurement of ECL intensity after further magnetic beads separation. Our results show that the anti-ZIKV-PSBs …