DOCSLIB.ORG

ATALIS-DISSERTATION-2021.Pdf

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
ATALIS-DISSERTATION-2021.Pdf EVALUATING THE EFFECTS OF PARTICLE-DELIVERED COMBINATION ADJUVANTS ON ANTIGEN-PRESENTING CELLS A Dissertation Presented to The Academic Faculty by Alexandra Maria Atalis In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University May 2021 COPYRIGHT © 2021 BY ALEXANDRA MARIA ATALIS EVALUATING THE EFFECTS OF PARTICLE-DELIVERED COMBINATION ADJUVANTS ON ANTIGEN-PRESENTING CELLS Approved by: Dr. Krishnendu Roy, Advisor Dr. Philip Santangelo School of Biomedical Engineering School of Biomedical Engineering Georgia Institute of Technology Georgia Institute of Technology Dr. J. Brandon Dixon, Co-Advisor Dr. Manmohan Singh School of Mechanical Engineering Senior VP, Pharmaceutical Sciences Georgia Institute of Technology and Delivery Technologies Beam Therapeutics Dr. Susan Thomas School of Mechanical Engineering Georgia Institute of Technology Date Approved: February 12, 2021 To my mom, Elaine Atalis, in loving memory ACKNOWLEDGEMENTS I would like to acknowledge all current and previous labmates who helped me throughout my Ph.D. journey. Dr. Jardin Leleux, Dr. Pallab Pradhan, Dr. Randall Toy, and Dr. Timothy Kassis taught me the basics of experimental design and foundational lab techniques and provided much-needed encouragement and motivation. Dr. Bhawana Pandey helped tremendously by preparing particle formulations for most experiments in Aim 2 and provided many chemistry-related experimental tips. When times were tough, she reminded me to stay positive. Cole Keenum and Alexander Beach were a big part of the COVID-19 research team. Alex collected BMDC cytokine and serological antibody titer data from ELISA and Luminex assays. Cole helped with preparing particle formulations, ELISA assays, and staining samples for flow cytometry. Paramita Chatterjee and Angela Jimenez performed RT-PCR experiments and data analysis. Paramita Chatterjee and Cole Keenum provided the single-cell mRNA and protein expression data analyzed in SEURAT. A big team worked on the COVID-19 intranasal vaccination study: Bhawana Pandey, Pallab Pradhan, Alexander Beach, Cole Keenum, Ritika Jain, Casey Vantucci, and Justin Hosten. Thank you to my advisors, Dr. Roy and Dr. Dixon, for all of their guidance and support, especially when I had to take a personal hiatus to spend time with family. To Dr. Dixon: I will never forget when attended the Lymphatics Gordon Research Conference in Italy with LLBB. Thank you for allowing me that opportunity. To Dr. Roy: it is hard to believe I have known you for over 10 years since I was a sophomore at UT Austin. I remember sitting in the lobby of the Biomedical Engineering Building wondering what I would do after college, and you encouraged me to apply to graduate school. Finally, thank you to my friends and family who have supported me through the iv ups and downs. My roommate and friend, Dr. Roxanne Glazier, and I had many late-night talks about life and research that I will never forget. My close friend and confidante, Michelle Humphrey, was always a phone call away when times were tough (and thank you for the box of snacks to help me get through writing this dissertation). My godfather, Dr. John Pappadas has been my #1 fan since Day 1 of starting this program. He supported me through my anxiety and encouraged me to stick with it. Thank you to my brothers, Sam and John, and to cousins, aunts, uncles, and Yiayias who provided much love and prayer. Thank you to my Dad, Andy Atalis, who was always there to talk me through the tough moments and has encouraged me to be my best self. Thank you to my husband-to-be Nick Grivas, who is my rock. I look forward to our marriage and life together. Finally, I want to acknowledge my mother, Elaine Atalis, who passed away in 2017. Her strength continually inspires me to persevere through difficult moments. She is with me in spirit every step of the way. v TABLE OF CONTENTS ACKNOWLEDGEMENTS iv LIST OF TABLES ix LIST OF FIGURES x LIST OF SYMBOLS AND ABBREVIATIONS xiii SUMMARY xv Chapter 1: Introduction and Aims 1 1.1 Introduction 1 1.2 Specific Aims 7 1.2.1 Hypothesis 7 1.2.2 Aim 1: Characterizing Immune Responses to Combined MPLA and CpG 8 1.2.3 Aim 2: Characterizing Immune Responses to Combined RLR and TLR Agonists 9 Chapter 2: Background 12 2.1 APCs: Linking Innate and Adaptive Immunity 12 2.2 Pathogen Recognition Receptors 19 2.2.1 Toll-like Receptors 19 2.2.2 RIG-I-like Receptors 24 2.3 APC Subsets and their Functions 25 2.3.1 Conventional DCs 26 2.3.2 Monocyte-derived DCs 28 2.3.3 Plasmacytoid DCs 29 2.3.4 Macrophages 30 2.3.5 B Cells 32 2.3.6 In Vitro Models of APCs 33 2.4 PRR Agonists as Vaccine Adjuvants 33 2.4.1 Monophosphoryl Lipid A (TLR4) 35 2.4.2 Imiquimod and Resiquimod (TLR7/8) 35 2.4.3 CpG Oligodeoxynucleotides (TLR9) 36 2.4.4 RIG-I-Like Receptor Ligands 37 2.4.5 Combination Adjuvants 38 2.5 Vaccine Delivery to Lymph Nodes 39 2.5.1 Particle-Based Vaccine Delivery 39 2.5.2 Dendritic Cell Migration Through Lymphatic Vessels 40 2.6 Adjuvants in SARS-CoV-2 Vaccines 41 Chapter 3: Aim 1.1. Investigating How Soluble and Particle-based Delivery of MPLA and CpG Differentially Modulate 3D Chemotaxis of Bone Marrow-Derived Dendritic Cells 44 vi 3.1 Materials and Methods 45 3.1.1 Bone marrow-derived cells (BMDCs) 45 3.1.2 Synthesis of PLGA Microparticles 46 3.1.3 Flow Cytometry Experiments 46 3.1.4 Microfluidic Device Setup 49 3.1.5 Cell Tracking 50 3.1.6 Statistical Analysis 50 3.2 Results 52 3.2.1 Synthesis of PLGA Microparticles for Dual Adjuvant Delivery 52 3.2.2 Generation of Heterogenous Cell Populations in BMDC Culture 53 3.2.3 Logistic Regression Model Filters Data for Migratory Cell Tracks 56 3.2.4 Addition of IL-4 to BMDC Culture Increases CCR7 Expression and Chemotaxis 59 3.2.5 Soluble MPLA Increases While Soluble CpG Decreases Chemotaxis 62 3.2.6 CpG Delivered on PLGA MP Increases Cell Chemotaxis 64 3.3 Discussion 66 Chapter 4: Aim 1.2. Assessing How MPLA and CpG Regulate Immune Cell Populations and Particle Transport to Draining Lymph Nodes In Vivo 73 4.1 Materials and Methods 73 4.1.1 Synthesis of Fluorescent Nanoparticles 73 4.1.2 Intramuscular Injections 75 4.1.3 NIR Imaging of Lymph Nodes 75 4.1.4 Tissue Preparation and Staining for Flow Cytometry 76 4.1.5 Statistical Analysis 78 4.2 Results 78 4.2.1 Fluorescence of IR700-Conjugated CpG and Control ODN Loaded on PLGA PEI NP Peaks at 24 Hours and Decreases at 48 Hours in Muscle-Draining Lymph Nodes 78 4.2.2 Particle-Delivered MPLA and CpG ODN Differentially Regulate Innate Immune Cell Populations and Maturation in the Muscle 82 4.2.3 MPLA and CpG ODN Loaded on PLGA PEI NP Differentially Regulate APC Populations and CD86 Expression in Muscle-Draining Lymph Nodes 86 Chapter 5: Aim 2.1. Evaluating How RLR- and TLR-Tarteting PLGA Nanoparticles Direct Bone Marrow-Derived DC Cytokine Secretion and T cell Activation In Vitro 88 4.3 Motivation 88 4.4 Materials and Methods 88 4.4.1 Synthesis of PUUC RNA 88 4.4.2 Preparation of PLGA-PEI Nanoparticles and Loading of Adjuvants 89 4.4.3 Bone-marrow derived Dendritic Cell (BMDC) Culture 90 4.4.4 Characterizing APC Subsets in BMDC Culture with Flow Cytometry 90 4.4.5 Iso-Mixed Lymphocyte Reaction 91 4.4.6 Analysis of BMDC Cytokine Secretion 92 4.5 Results 93 vii 4.5.1 FLT3L and GM-CSF Bone Marrow-Derived Dendritic Cell Cultures are Comprised of Different APC Subsets 93 4.5.2 GM-CSF and FLT3L BMDC Secrete Distinct Cytokine Patterns in Response to Combination Adjuvants 93 4.5.3 GM-CSF and FLT3L BMDCs Selectively Respond to PRR-Targeted Adjuvants to Induce CD8+ T Cell Proliferation and T Cell Death in Iso-MLR Assay 100 Chapter 6: Aim 2.2. Characterizing Innate and Adaptive Immune Responses to Intranasal Vaccination with Co-Delivered RLR and TLR agonists on PLGA Nanoparticles 103 5.1 Materials and Methods 103 5.1.1 Intranasal Administration of PLPs 103 5.1.2 Lung Gene Expression Analysis with RT-PCR 103 5.1.3 Single-Cell Gene and Protein Expression Analysis with CITE-Seq 105 5.1.4 SARS-CoV-2 Vaccination Groups 106 5.1.5 Preparation of Spike Protein-Conjugated PLGA PEI NPs 107 5.1.6 Vaccination Timeline and Tissue Collection 108 5.1.7 IgG and IgA ELISA Assays 108 5.1.8 Ex Vivo Lung Cell Stimulation Assays 109 5.1.9 Intracellular Cytokine Staining 110 5.2 Results 111 5.2.1 PUUC-TLR Agonist Combinations Differentially Regulate Inflammatory Gene Expression in Mouse Lungs after Intranasal Administration 111 5.2.2 CITE-Seq Analysis Reveals Changes in Lung Cell Populations and Genetic Expression in Response to PUUC and MPLA-PUUC PLGA NPs 116 5.2.3 MPLA-PUUC NP Increase CD4+ and CD103+CD69+ T Cell Responses to Restimulation with SARS-CoV-2 Spike Peptide Pools 119 Chapter 7: Conclusions and Future Work 123 6.1 Conclusions 123 6.1.1 APC-Mediated Immune Responses to Combination Adjuvants In Vitro are Dependent on the Type of APC Culture 123 6.1.2 APC-mediated Immune Responses to Combination Adjuvants and Antigens are Dependent on Vaccine Delivery Systems 125 6.1.3 Route of Administration Determines Success for Combination Adjuvants 126 6.2 Future Work 129 Appendix A: Supplementary Figures and Methods 132 8.1 Aim 1.1 Supporting Information 132 8.1.1 Supplemental Experimental Methods 132 8.1.2 Circular Statistical Methods 133 8.1.3 Supplemental Figures 138 8.2 Aim 1.2 Supporting Information 144 8.3 Aim 2.1 Supporting Information 146 8.4 Aim 2.2 Supporting Information 149 References 156 viii LIST OF TABLES Table 1 Single and combination adjuvant loading on PLGA NP and doses for 92 BMDC culture.
Load more

Recommended publications
  • Mrna Vaccine: a Potential Therapeutic Strategy Yang Wang† , Ziqi Zhang† , Jingwen Luo† , Xuejiao Han† , Yuquan Wei and Xiawei Wei*
    Wang et al. Molecular Cancer (2021) 20:33 https://doi.org/10.1186/s12943-021-01311-z REVIEW Open Access mRNA vaccine: a potential therapeutic strategy Yang Wang† , Ziqi Zhang† , Jingwen Luo† , Xuejiao Han† , Yuquan Wei and Xiawei Wei* Abstract mRNA vaccines have tremendous potential to fight against cancer and viral diseases due to superiorities in safety, efficacy and industrial production. In recent decades, we have witnessed the development of different kinds of mRNAs by sequence optimization to overcome the disadvantage of excessive mRNA immunogenicity, instability and inefficiency. Based on the immunological study, mRNA vaccines are coupled with immunologic adjuvant and various delivery strategies. Except for sequence optimization, the assistance of mRNA-delivering strategies is another method to stabilize mRNAs and improve their efficacy. The understanding of increasing the antigen reactiveness gains insight into mRNA-induced innate immunity and adaptive immunity without antibody-dependent enhancement activity. Therefore, to address the problem, scientists further exploited carrier-based mRNA vaccines (lipid-based delivery, polymer-based delivery, peptide-based delivery, virus-like replicon particle and cationic nanoemulsion), naked mRNA vaccines and dendritic cells-based mRNA vaccines. The article will discuss the molecular biology of mRNA vaccines and underlying anti-virus and anti-tumor mechanisms, with an introduction of their immunological phenomena, delivery strategies, their importance on Corona Virus Disease 2019 (COVID-19) and related clinical trials against cancer and viral diseases. Finally, we will discuss the challenge of mRNA vaccines against bacterial and parasitic diseases. Keywords: mRNA vaccine, Self-amplifying RNA, Non-replicating mRNA, Modification, Immunogenicity, Delivery strategy, COVID-19 mRNA vaccine, Clinical trials, Antibody-dependent enhancement, Dendritic cell targeting Introduction scientists are seeking to develop effective cancer vac- A vaccine stimulates the immune response of the body’s cines.
    [Show full text]
  • Resiquimod As an Immunologic Adjuvant for NY-ESO-1 Protein
    Published OnlineFirst January 29, 2015; DOI: 10.1158/2326-6066.CIR-14-0202 Research Article Cancer Immunology Research Resiquimod as an Immunologic Adjuvant for NY-ESO-1 Protein Vaccination in Patients with High-Risk Melanoma Rachel Lubong Sabado1,2, Anna Pavlick1, Sacha Gnjatic2,3, Crystal M. Cruz1, Isabelita Vengco1, Farah Hasan1, Meredith Spadaccia1, Farbod Darvishian4, Luis Chiriboga4, Rose Marie Holman1, Juliet Escalon1, Caroline Muren1, Crystal Escano1, Ethel Yepes1, Dunbar Sharpe1, John P.Vasilakos5, Linda Rolnitzsky6, Judith D. Goldberg6, John Mandeli2, Sylvia Adams1, Achim Jungbluth7, Linda Pan3, Ralph Venhaus3, Patrick A. Ott1,8, and Nina Bhardwaj1,2,4 Abstract The Toll-like receptor (TLR) 7/8 agonist resiquimod has been vaccine regimens were generally well tolerated. NY-ESO-1–specific used as an immune adjuvant in cancer vaccines. We evaluated the humoral responses were induced or boosted in all patients, many safety and immunogenicity of the cancer testis antigen NY-ESO-1 of whom had high titer antibodies. In part II, 16 of 20 patients in þ þ given in combination with Montanide (Seppic) with or without both arms had NY-ESO-1–specificCD4 T-cell responses. CD8 T- resiquimod in patients with high-risk melanoma. In part I of the cell responses were only seen in 3 of 12 patients in arm B. Patients study, patients received 100 mg of full-length NY-ESO-1 protein with TLR7 SNP rs179008 had a greater likelihood of developing þ emulsified in 1.25 mL of Montanide (day 1) followed by topical NY-ESO-1–specificCD8 responses. In conclusion, NY-ESO-1 application of 1,000 mg of 0.2% resiquimod gel on days 1 and 3 protein in combination with Montanide with or without topical þ (cohort 1) versus days 1, 3, and 5 (cohort 2) of a 21-day cycle.
    [Show full text]
  • Polymeric Biomaterial Drug Delivery Systems for Glioblastoma Therapy and Vaccines
    POLYMERIC BIOMATERIAL DRUG DELIVERY SYSTEMS FOR GLIOBLASTOMA THERAPY AND VACCINES Kathryn Margaret Moore A dissertation submitted to the faculty at the University of North Carolina at Chapel Hill in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Biomedical Engineering in the School of Medicine. Chapel Hill 2020 Approved by: Kristy M. Ainslie David Zaharoff Yevgeny Brudno Shawn D. Hingtgen Aaron Anselmo 2020 Kathryn Margaret Moore ALL RIGHTS RESERVED ii ABSTRACT Kathryn Margaret Moore: Polymeric Biomaterial Drug Delivery Systems for Glioblastoma Therapy and Vaccines (Under the direction of Kristy M. Ainslie) Polymeric biomaterial drug delivery systems have been explored to improve therapies for a wide range of diseases, including cancer and infectious diseases, by providing control over delivery of therapeutic cargo. Scaffolds composed of polymeric biomaterials have been used to increase efficacy of cell therapies by promoting cell implantation and viability thereafter. Both scaffolds and particles can be loaded with small molecules and biological agents to enhance delivery to target cells. This dissertation aims to explore the use of polymeric biomaterials to improve both glioblastoma therapy and vaccines. In the case of glioblastoma, the most common primary brain tumor, local drug delivery is a beneficial therapeutic strategy because its bypasses the blood brain barrier and allows for direct access to the site of tumor recurrence. Herein, scaffolds were fabricated by the process of electrospinning and characterized for the delivery of tumoricidal agent producing stem cells and chemotherapeutics into the glioblastoma surgical resection cavity. This work places a strong emphasis on the impact of scaffold degradation on the local glioblastoma therapies by utilizing the tunable polymer, acetalated dextran.
    [Show full text]
  • Download Preprint
    Vaccine containing immunologic adjuvants with a wide range of activity to provide protection against COVID-19 Author: Mulugeta Berhanu, Ethiopian Agricultural Transformation Agency Email: [email protected]; Tel:+251921433836 Abstract COVID-19 is a devastating viral disease which can be prevented by vaccination. Immunologic adjuvants are key to develop an effective vaccines against infectious diseases in human and non- human primates. Vaccines containing an appropriate adjuvants are crucial for the prevention of various infectious diseases which are the biggest threats to human and animal health. This paper proposes a wide spectrum immunologic adjuvant for vaccine development against COVID-19 which is the current global problem. It has been reported that a wide range of immune cells are involved in the body’s response to SARS CoV2 infection. Therefore, vaccine with a wide- spectrum immunologic adjuvant can be used to provide protection against COVID-19. Lack of adjuvants that can induce the required immune responses is a serious impediment to vaccine development against this devastating virus. The approved adjuvants such as aluminum salts and MF59 exhibit a narrow range of activity. In an attempt to solve this problem, it is crucial to develop new adjuvants which can trigger a wide range of immune cells. Key words: Adjuvants for COVID-19 vaccines, Aluminum salts, COVID-19, Immunologic adjuvants, MF-59, SARS CoV2, Vaccine development against COVID-19, Vaccine with a wide- spectrum immunologic adjuvant 1. Introduction Vaccine has played a critical role in protecting the global community from various infectious diseases. Vaccine development against COVID-19 is hindered by lack of approved adjuvants that can induce the desired immune responses.
    [Show full text]
  • Innate Immune Response Against Hepatitis C Virus: Targets for Vaccine Adjuvants
    Review Innate Immune Response against Hepatitis C Virus: Targets for Vaccine Adjuvants , , Daniel Sepulveda-Crespo , Salvador Resino * y and Isidoro Martinez * y Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28220 Madrid, Spain; [email protected] * Correspondence: [email protected] (S.R.); [email protected] (I.M.); Tel.: +34-91-8223266 (S.R.); +34-91-8223272 (I.M.); Fax: +34-91-5097919 (S.R. & I.M.) Both authors contributed equally to this study. y Received: 1 June 2020; Accepted: 16 June 2020; Published: 17 June 2020 Abstract: Despite successful treatments, hepatitis C virus (HCV) infections continue to be a significant world health problem. High treatment costs, the high number of undiagnosed individuals, and the difficulty to access to treatment, particularly in marginalized susceptible populations, make it improbable to achieve the global control of the virus in the absence of an effective preventive vaccine. Current vaccine development is mostly focused on weakly immunogenic subunits, such as surface glycoproteins or non-structural proteins, in the case of HCV. Adjuvants are critical components of vaccine formulations that increase immunogenic performance. As we learn more information about how adjuvants work, it is becoming clear that proper stimulation of innate immunity is crucial to achieving a successful immunization. Several hepatic cell types participate in the early innate immune response and the subsequent inflammation and activation of the adaptive response, principally hepatocytes, and antigen-presenting cells (Kupffer cells, and dendritic cells). Innate pattern recognition receptors on these cells, mainly toll-like receptors, are targets for new promising adjuvants. Moreover, complex adjuvants that stimulate different components of the innate immunity are showing encouraging results and are being incorporated in current vaccines.
    [Show full text]
  • Cytolytic Perforin As an Adjuvant to Enhance the Immunogenicity of DNA Vaccines
    vaccines Review Cytolytic Perforin as an Adjuvant to Enhance the Immunogenicity of DNA Vaccines Ashish C. Shrestha * , Danushka K. Wijesundara, Makutiro G. Masavuli, Zelalem A. Mekonnen, Eric J. Gowans and Branka Grubor-Bauk * Virology Laboratory, Discipline of Surgery, Basil Hetzel Institute for Translational Health Research and University of Adelaide, Adelaide 5011, Australia; [email protected] (D.K.W.); [email protected] (M.G.M.); [email protected] (Z.A.M.); [email protected] (E.J.G.) * Correspondence: [email protected] (A.C.S.); [email protected] (B.G.-B.); Tel.: +61-8-8222-6590 (A.C.S.); +61-8-8222-7368 (B.G.-B.) Received: 8 March 2019; Accepted: 25 April 2019; Published: 30 April 2019 Abstract: DNA vaccines present one of the most cost-effective platforms to develop global vaccines, which have been tested for nearly three decades in preclinical and clinical settings with some success in the clinic. However, one of the major challenges for the development of DNA vaccines is their poor immunogenicity in humans, which has led to refinements in DNA delivery, dosage in prime/boost regimens and the inclusion of adjuvants to enhance their immunogenicity. In this review, we focus on adjuvants that can enhance the immunogenicity of DNA encoded antigens and highlight the development of a novel cytolytic DNA platform encoding a truncated mouse perforin. The application of this innovative DNA technology has considerable potential in the development of effective vaccines. Keywords: DNA vaccine; adjuvants; vaccine delivery; plasmid; cytolytic; perforin; bicistronic; HCV; HIV 1.
    [Show full text]
  • Double Chimeric Peptide Vaccine and Monoclonal Antibodies That Protect
    ccines & a V f V a o c l c i a n n a r t u i o o n J Xin, J Vaccines Vaccin 2014, 5:4 Journal of Vaccines & Vaccination DOI: 10.4172/2157-7560.1000241 ISSN: 2157-7560 Research Article Open Access Double Chimeric Peptide Vaccine and Monoclonal Antibodies that Protect Against Disseminated Candidiasis Hong Xin* Department of Pediatrics, Louisiana State University Health Sciences Center and Research Institute for Children, Children's Hospital, New Orleans, Louisiana 70118, USA *Corresponding author: Hing Xin, Research Institute for Children, Children’s Hospital, 200 Henry Clay Ave, New Orleans, LA 70118, USA, Tel: (504) 896-2912; Fax: (504) 896-9413; E-mail: [email protected] Received date: 22 May 2014; Accepted date: 26 June 2014; Published date: 30 June 2014 Copyright: © 2014 Xin H. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract A double chimeric peptide vaccine, targeting two peptides (Fba and Met6) expressed on the cell surface of Candida albicans, can induce high degree of protection against disseminated candidiasis in mice. Although immunization with each individual peptide vaccine was effective in protection against the disease, immunization with the double chimeric peptide vaccine, not two- peptide mixture, induced better protective immunity than that induced by each individual peptide vaccine. Passive transfer of immune sera from peptide immunized mice demonstrated that the protection was medicated by peptide-specific antibodies. Furthermore, we combined two protective MAbs, including Fba peptide specific IgM E2-9 and Met6 peptide specific IgG3 M2-4, into one cocktail and evaluated it for protective efficacy, side by side with each protective MAb given alone.
    [Show full text]
  • The Jordan Report 20Th Anniversary: Accelerated Development Of
    USA ES IC V R E S N A M U H & D H H E T P L A A R E T H M F F E N O T Accelerated Development of Vaccines Preface In 1982, the National Institute of Allergy and Infectious Dis­ Along with these technological advances, there has been a eases (NIAID) established the Program for the Accelerated heightened awareness of the importance of vaccines for global Development of Vaccines. For 20 years, this program has helped health and security. Acquired immunodeficiency syndrome stimulate the energy, intellect, and ability of scientists in micro­ (AIDS), malaria, and tuberculosis have demonstrated to the biology, immunology, and infectious diseases. Vaccine research world the importance of public health in economic development. has certainly benefited. The status report reflecting this Most recently, the threat of bioterrorism has reminded many progress in vaccine research has come to be known as the Jor­ Americans of the value of vaccines as public health tools. dan Report in recognition of Dr. William Jordan, past director of NIAID’s Division of Microbiology and Infectious Diseases Articles by outside experts in this edition highlight many of the (DMID) and the program’s earliest advocate. scientific advances, challenges, and issues of vaccine research during these two decades. As we look to the decade ahead, the This anniversary edition of the Jordan Report summarizes 20 payoffs from basic research will continue to invigorate vaccine years of achievements in vaccine research driven by the explo­ development, but economic, risk communication, and safety sive technological advances in genomics, immunology, and challenges are likely to influence the licensing of new vaccines.
    [Show full text]
  • Increased Cellular Immunity Against Host Cell Antigens Induced by Vacciniavirus (With 2 Figures) 122
    Archiv für die gesamte Virusforschung Begründet von R. Doerr Herausgegeben von S. Gard, Stockholm C. Hallauer, Bern A. Mayr, München W. P. Rowe, Bethesda, Md. J.Vilcek, New York, N.Y. Vol. 45, 1974 Springer-Verlag Wien New York Archiv für die gesamte Virusforschung Editorial Advisory Board / Fachbeirat V. H. Bonifas, Lausanne F. Steck, Bern J. Casals, New Haven, Conn. J. H. Subak-Sharpe, Glasgow Η. Hanafusa, New York, N.Y. Η. M. Temin, Madison, Wis. W.K.Joklik, Durham, N.C. D. A. J. Tyrrell, Harrow M. Kitaoka, Tokyo J. D. Verlinde, Leiden K. Maramorosch, Yonkers, N.Y. A. P. Waterson, London M. Matumoto, Tokyo R. Weil, Geneve M. Mussgay, Tübingen Κ. E. Weiss, Onderstepoort E. Norrby, Stockholm H. A. Wenner, Kansas City, Mo. W.Plowright, London V. M. Zhdanov, Moscow Editorial Assistant / Redaktionssekretär: F. Heinz, Wien The exclusive copyright for all languages and countries, including the right for photo• mechanical and any other reproductions including microform is transferred to the publisher. Alle Rechte, einschließlich das der Übersetzung in fremde Sprachen und das der photo• mechanischen Wiedergabe oder einer sonstigen Vervielfältigung, auch in Mikroform, vor• behalten. © 1974 by Springer-Verlag / Wien Contents/Inhalt: Vol. 45 No. 1—2 Kalinina, Natalya O., Irina V. Scarlat, and V. I. Agol: The Synthesis of Virus-Specific Polypeptides on Polyribosomes Isolated from the Cells In• fected with Encephalomyocarditis Virus (With 3 Figures) 1 Ozaki, Υ., K. Kumagai, M. Kawanishi, and A. Seto: Studies on the Neutra­ lization of Japanese Encephalitis Virus. III. Analysis of the Neutralization Reaction by Anti-Rabbit-y-Globulin Serum (With 2 Figures) 7 Dmitrieva, Τ.
    [Show full text]
  • Artículos Científicos
    Editor: NOEL GONZÁLEZ GOTERA Número 173 Diseño: Lic. Roberto Chávez y Liuder Machado. Semana 310115 - 060215 Foto: Lic. Belkis Romeu e Instituto Finlay La Habana, Cuba. ARTÍCULOS CIENTÍFICOS Publicaciones incluidas en PubMED durante el período comprendido entre el 31 de enero y el 6 de febrero de 2015. Con “vaccin*” en título: 121 artículos recuperados. Vacunas meningococo (Neisseria meningitidis) 47. Low immunogenicity of quadrivalent meningococcal vaccines in solid organ transplant recipients. Wyplosz B, Derradji O, Hong E, François H, Durrbach A, Duclos-Vallée JC, Samuel D, Escaut L, Launay O, Vittecoq D, -K Taha M. Transpl Infect Dis. 2015 Jan 31. doi: 10.1111/tid.12359. [Epub ahead of print] PMID: 25645691 [PubMed - as supplied by publisher] Related citations Select item 25645600 102. Serogroup A meningococcal conjugate (PsA-TT) vaccine coverage and measles vaccine coverage in Burkina Faso-Implications for introduction of PsA-TT into the Expanded Programme on Immunization. Meyer SA, Kambou JL, Cohn A, Goodson JL, Flannery B, Medah I, Messonnier N, Novak R, Diomande F, Djingarey MH, Clark TA, Yameogo I, Fall A, Wannemuehler K. Vaccine. 2015 Jan 27. pii: S0264-410X(15)00087-0. doi: 10.1016/j.vaccine.2015.01.043. [Epub ahead of print] PMID: 25636915 [PubMed - as supplied by publisher] Related citations 1 Select item 25636714 Vacunas BCG – ONCO BCG (Mycobacterium bovis) 12. Comparative evaluation of booster efficacies of BCG, Ag85B, and Ag85B peptides based vaccines to boost BCG induced immunity in BALB/c mice: a pilot study. Husain AA, Warke SR, Kalorey DR, Daginawala HF, Taori GM, Kashyap RS. Clin Exp Vaccine Res.
    [Show full text]
  • Immunization of High-Risk Breast Cancer Patients with Clustered Stn-KLH Conjugate Plus the Immunologic Adjuvant QS-21 Teresa A
    Cancer Therapy: Clinical Immunization of High-Risk Breast Cancer Patients with Clustered sTn-KLH Conjugate plus the Immunologic Adjuvant QS-21 Teresa A. Gilewski,1Govind Ragupathi,1Maura Dickler,1Shemeeakah Powell,1Sonal Bhuta,1 Kathy Panageas,1R. Rao Koganty,2 Jeannette Chin-Eng,1Clifford Hudis,1Larry Norton,1 Alan N. Houghton,1and Philip O. Livingston1 Abstract Purpose: To determine the clinical toxicities and antibody response against sTnand tumor cells expressing sTnfollowing immunization of high-risk breast cancer patients with clustered sTn-KLH [sTn(c)-KLH] conjugate plus QS-21. Experimental Design:Twenty-seven patients with no evidence of disease and with a history of either stage IV no evidence of disease, rising tumor markers, stage II (z4 positive axillary nodes), or stage III disease received a total of five injections each during weeks 1, 2, 3, 7, and 19. Immuni- zations consisted of sTn(c)-KLH conjugate containing 30, 10, 3, or 1 Ag sTn(c) plus 100 Ag QS-21. Induction of IgM and IgG antibodies against synthetic sTn(c) and natural sTn on ovine submaxillary mucin were measured before and after therapy. Fluorescence-activated cell sorting analyses assessed reactivity of antibodies to LSC and MCF-7 tumor cells. Results: The most common toxicities were transient local skin reactions at the injection site and mild flu-like symptoms. All patients developed significant IgM and IgG antibody titers against sTn(c). Antibody titers against ovine submaxillary mucin were usually of lower titers. IgM reactiv- ity with LSC tumor cells was observed in 21patients and with MCF-7 cells in 13 patients.
    [Show full text]
  • Efficacy and Safety of COVID-19 Vaccines: a Systematic Review and Meta-Analysis of Randomized Clinical Trials
    Review Efficacy and Safety of COVID-19 Vaccines: A Systematic Review and Meta-Analysis of Randomized Clinical Trials Ali Pormohammad 1, Mohammad Zarei 2, Saied Ghorbani 3 , Mehdi Mohammadi 1 , Mohammad Hossein Razizadeh 3 , Diana L. Turner 4 and Raymond J. Turner 1,* 1 Department of Biological Sciences, University of Calgary, Calgary, AB T2N 1N4, Canada; [email protected] (A.P.); [email protected] (M.M.) 2 John B. Little Center for Radiation Sciences, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; [email protected] 3 Department of Virology, Faculty of Medicine, Iran University of Medical Science, Tehran 1449614535, Iran; [email protected] (S.G.); [email protected] (M.H.R.) 4 Department of Family Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; [email protected] * Correspondence: [email protected]; Tel.: +1-(403)-220-4308 Abstract: The current study systematically reviewed, summarized and meta-analyzed the clinical features of the vaccines in clinical trials to provide a better estimate of their efficacy, side effects and immunogenicity. All relevant publications were systematically searched and collected from major Citation: Pormohammad, A.; Zarei, databases up to 12 March 2021. A total of 25 RCTs (123 datasets), 58,889 cases that received the M.; Ghorbani, S.; Mohammadi, M.; COVID-19 vaccine and 46,638 controls who received placebo were included in the meta-analysis. In Razizadeh, M.H.; Turner, D.L.; Turner, total, mRNA-based and adenovirus-vectored COVID-19 vaccines had 94.6% (95% CI 0.936–0.954) R.J.
    [Show full text]